Descriptor: "MESH: Platelet Aggregation Inhibitors" - Searchworks@Jio Institute Digital Library Search Results

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43 results on '"MESH: Platelet Aggregation Inhibitors"'

1. Derivation, Validation, and Prognostic Utility of a Prediction Rule for Nonresponse to Clopidogrel

Author: Dominick J. Angiolillo, Davide Capodanno, Thomas O. Bergmeijer, Tabassome Simon, Dirk Sibbing, Nicolas Danchin, Jurriën M. ten Berg, Matthew J. Price, Centre de Ressources Biologiques APHP-SU (PASS-CRB-APHP-SU), Unité Mixte de Service Production et Analyse de données en Sciences de la vie et en Santé (PASS), and Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: MESH: Coronary Thrombosis, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, outcomes, MESH: Risk Assessment, 0302 clinical medicine, P2Y12, MESH: Risk Factors, risk factors, MESH: Obesity, 030212 general & internal medicine, Myocardial infarction, MESH: Treatment Outcome, 2. Zero hunger, MESH: Aged, Framingham Risk Score, MESH: Middle Aged, Clopidogrel, MESH: Predictive Value of Tests, 3. Good health, MESH: Reproducibility of Results, MESH: Myocardial Infarction, MESH: Platelet Aggregation Inhibitors, MESH: Drug Resistance, MESH: Purinergic P2Y Receptor Antagonists, Cardiology and Cardiovascular Medicine, MESH: Percutaneous Coronary Intervention, medicine.drug, medicine.medical_specialty, MESH: Diabetes Mellitus, MESH: Renal Insufficiency, Chronic, CYP2C19, genetic testing, MESH: Body Mass Index, MESH: Clinical Decision Rules, 03 medical and health sciences, Internal medicine, Diabetes mellitus, medicine, cardiovascular diseases, MESH: Age Factors, clopidogrel, MESH: Pharmacogenomic Variants, MESH: Humans, business.industry, MESH: Time Factors, MESH: Clopidogrel, medicine.disease, MESH: Databases, Factual, MESH: Male, MESH: Randomized Controlled Trials as Topic, MESH: Cytochrome P-450 CYP2C19, business, Body mass index, MESH: Female, Kidney disease
Abstract: Objectives The aim of this study was to develop a risk score integrating cytochrome P450 2C19 loss-of-function genotypes with clinical risk factors influencing clopidogrel response that would allow the identification with more precision of subjects at risk for high platelet reactivity (HPR) and adverse clinical outcomes. Background Clopidogrel is the most broadly used platelet P2Y12 inhibitor. However, a considerable number of patients achieve inadequate platelet inhibition, with persistent HPR, an established marker of increased thrombotic risk, underscoring the need for tools to help identify these subjects. Although carriers of loss-of-function alleles of the cytochrome P450 2C19 enzyme have reduced clopidogrel metabolism leading to increased rates of HPR and thrombotic complications, this explains only a fraction of the pharmacodynamic response to clopidogrel, and a number of clinical factors have also been shown to have contributing roles. Methods Three prospective and independent studies were used to: 1) develop a risk score integrating genetic and clinical factors to identify patients with HPR while on clopidogrel; 2) investigate the external validity of the risk score; and 3) define clinical outcomes associated with the risk score in a cohort of patients with myocardial infarction treated with clopidogrel. Results A risk score ABCD-GENE (Age, Body Mass Index, Chronic Kidney Disease, Diabetes Mellitus, and Genotyping) was developed incorporating 5 independent predictors of HPR: 4 clinical (age >75 years, body mass index >30 kg/m2, chronic kidney disease [glomerular filtration rate Conclusions The ABCD-GENE score is a simple tool to identify patients with HPR on clopidogrel and who are at increased risk for adverse ischemic events, including mortality, following an acute myocardial infarction. In patients with a high ABCD-GENE score, long-term oral P2Y12 inhibitors other than clopidogrel should be considered.
Published: 2020

2. [Use of antiplatelet therapy and direct oral anticoagulants in candidates for renal transplantation: The French guidelines from the CTAFU]

Author: Timsit, M.-O., Branchereau, J., Matillon, X., Verhoest, G., Bessede, T., Lequintrec, M., Boissier, R., Badet, L., Smadja, D.M., Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), CHU Pontchaillou [Rennes], Hôpital Bicêtre, Hôpital Lapeyronie [Montpellier] (CHU), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Aix Marseille Université (AMU), and Hôpital de la Conception [CHU - APHM] (LA CONCEPTION)
Subjects: MESH: Humans, Antiplatelet therapy, [SDV]Life Sciences [q-bio], Anticoagulants, MESH: Preoperative Period, Kidney Transplantation, MESH: Kidney Transplantation, Agents antiplaquettaires, MESH: Platelet Aggregation Inhibitors, Preoperative Period, Renal Transplantation, Transplantation rénale, Humans, MESH: Factor Xa Inhibitors, Platelet Aggregation Inhibitors, Factor Xa Inhibitors
Abstract: International audience; Objective: To define guidelines for the use of antiplatelet therapy (AT) and direct oral anticoagulants (DOAC) in candidates for kidney allotransplantation.Method: A review of the medical literature following a systematic approach was conducted by the CTAFU to report the use of AT and DOAC before major surgery and in the setting of advanced chronic kidney disease, defining their managment prior to kidney transplantation with the corresponding level of evidence.Results: DOAC are not recommended in patients under dialysis. Aspirin therapy, but not anti-P2Y12 and DOAC, may be maintained during renal transplantation. Anti-P2Y12 and DOAC should not be use in patients awaiting a kidney transplant, except when a living donor is scheduled, therefore authorizing treatment interruption in optimal conditions. Further data regarding DOAC reversion and monitoring may improve their use in this setting. Global level of evidence is weak.Conclusion: These French recommendations should contribute to improve surgical management of kidney transplant candidates exposed to AT or DOA.
Published: 2020

3. Rivaroxaban with or without aspirin in patients with stable peripheral or carotid artery disease: an international, randomised, double-blind, placebo-controlled trial

Author: Sonia S Anand, Jackie Bosch, John W Eikelboom, Stuart J Connolly, Rafael Diaz, Peter Widimsky, Victor Aboyans, Marco Alings, Ajay K Kakkar, Katalin Keltai, Aldo P Maggioni, Basil S Lewis, Stefan Störk, Jun Zhu, Patricio Lopez-Jaramillo, Martin O'Donnell, Patrick J Commerford, Dragos Vinereanu, Nana Pogosova, Lars Ryden, Keith A A Fox, Deepak L Bhatt, Frank Misselwitz, John D Varigos, Thomas Vanassche, Alvaro A Avezum, Edmond Chen, Kelley Branch, Darryl P Leong, Shrikant I Bangdiwala, Robert G Hart, Salim Yusuf, JORGELINA SALA, LUIS CARTASEGNA, MARISA VICO, MIGUEL ANGEL HOMINAL, EDUARDO HASBANI, ALBERTO CACCAVO, CESAR ZAIDMAN, DANIEL VOGEL, ADRIAN HRABAR, PABLO OMAR SCHYGIEL, CARLOS CUNEO, HUGO LUQUEZ, IGNACIO J. MACKINNON, RODOLFO ANDRES AHUAD GUERRERO, JUAN PABLO COSTABEL, INES PALMIRA BARTOLACCI, OSCAR MONTANA, MARIA BARBIERI, OSCAR GOMEZ VILAMAJO, RUBEN OMAR GARCIA DURAN, LILIA BEATRIZ SCHIAVI, MARCELO GARRIDO, ADRIAN INGARAMO, ANSELMO PAULINO BORDONAVA, MARIA JOSE PELAGAGGE, LEONARDO NOVARETTO, JUAN PABLO ALBISU DI GENNERO, LUZ MARIA IBANEZ SAGGIA, MOIRA ALVAREZ, NESTOR ALEJANDRO VITA, STELLA MARIS MACIN, RICARDO DARIO DRAN, MARCELO CARDONA, LUIS GUZMAN, RODOLFO JUAN SARJANOVICH, JESUS CUADRADO, SEBASTIAN NANI, MARCOS RAUL LITVAK BRUNO, CAROLINA CHACON, LAURA ELENA MAFFEI, DIEGO GRINFELD, NATALIA VENSENTINI, CLAUDIO RODOLFO MAJUL, HECTOR LUCAS LUCIARDI, PATRICIA DEL CARMEN GONZALEZ COLASO, FREDY ANTONI FERRE PACORA, PAUL VAN DEN HEUVEL, PETER VERHAMME, BAVO ECTOR, PHILIPPE DEBONNAIRE, PHILIPPE VAN DE BORNE, JEAN LEROY, HERMAN SCHROE, PASCAL VRANCKX, IVAN ELEGEERT, ETIENNE HOFFER, KARL DUJARDIN, CLARISSE INDIO DO BRASIL, DALTON PRECOMA, JOSE ANTONIO ABRANTES, EULER MANENTI, GILMAR REIS, JOSE SARAIVA, LILIA MAIA, MAURO HERNANDES, PAULO ROSSI, FABIO ROSSI DOS SANTOS, SERGIO LUIZ ZIMMERMANN, RAFAEL RECH, EDUARDO ABIB JR, PAULO LEAES, ROBERTO BOTELHO, OSCAR DUTRA, WEIMAR SOUZA, MARIA BRAILE, NILO IZUKAWA, JOSE CARLOS NICOLAU, LUIZ FERNANDO TANAJURA, CARLOS VICENTE SERRANO JUNIOR, CESAR MINELLI, LUIZ ANTONIO NASI, LIVIA OLIVEIRA, MARCELO JOSE DE CARVALHO CANTARELLI, RICHARD TYTUS, SHEKHAR PANDEY, EVA LONN, JAMES CHA, SAUL VIZEL, MOHAN BABAPULLE, ANDRE LAMY, KEVIN SAUNDERS, JOSEPH BERLINGIERI, BOB KIAII, RAKESH BHARGAVA, PRAVINSAGAR MEHTA, LAURIE HILL, DAVID FELL, ANDY LAM, FAISAL AL-QOOFI, CRAIG BROWN, ROBERT PETRELLA, JOSEPH A RICCI, ANTHONY GLANZ, NICOLAS NOISEUX, KEVIN BAINEY, FATIMA MERALI, MICHAEL HEFFERNAN, ANTHONY DELLA SIEGA, GILLES R DAGENAIS, FRANCOIS DAGENAIS, STEEVE BRULOTTE, MICHEL NGUYEN, MICHAEL HARTLEIB, RANDOLPH GUZMAN, RONALD BOURGEOIS, DENNIS RUPKA, YAARIV KHAYKIN, GILBERT GOSSELIN, THAO HUYNH, CLAUDE PILON, JEAN CAMPEAU, FRANCIS PICHETTE, ARIEL DIAZ, JAMES JOHNSTON, PRAVIN SHUKLE, GREGORY HIRSCH, PAUL RHEAULT, WLODZIMIERZ CZARNECKI, ANNIE ROY, SHAH NAWAZ, STEPHEN FREMES, DINKAR SHUKLA, GABRIEL JANO, JORGE LEONARDO COBOS, RAMON CORBALAN, MARCELO MEDINA, LEONARDO NAHUELPAN, CARLOS RAFFO, LUIS PEREZ, SERGIO POTTHOFF, BENJAMIN STOCKINS, PABLO SEPULVEDA, CHRISTIAN PINCETTI, MARGARITA VEJAR, HONGYAN TIAN, XUESI WU, YUANNAN KE, KAIYING JIA, PENGFEI YIN, ZHAOHUI WANG, LITIAN YU, SHULIN WU, ZONGQUI WU, SHAO WEN LIU, XIAO JUAN BAI, YANG ZHENG, PING YANG, YUN MEI YANG, JIWEI ZHANG, JUNBO GE, XIAO PING CHEN, JUNXIA LI, TAO HONG HU, RUIYAN ZHANG, ZHE ZHENG, XIN CHEN, LIANG TAO, JIANPING LI, WEIJIAN HUANG, GUOSHENG FU, CHUNJIAN LI, YUGANG DONG, CHUNSHENG WANG, XINMIN ZHOU, YE KONG, ARISTIDES SOTOMAYOR, JOSE LUIS ACCINI MENDOZA, HENRY CASTILLO, MIGUEL URINA, GUSTAVO AROCA, MARITZA PEREZ, DORA INES MOLINA DE SALAZAR, GREGORIO SANCHEZ VALLEJO, MANZUR J FERNANDO, HENRY GARCIA, LUIS HERNANDO GARCIA, EDGAR ARCOS, JUAN GOMEZ, FRANCISCO CUERVO MILLAN, FREDY ALBERTO TRUJILLO DADA, BORIS VESGA, GUSTAVO ADOLFO MORENO SILGADO, EVA ZIDKOVA, JEAN-CLAUDE LUBANDA, MARKETA KALETOVA, RADIM KRYZA, GABRIEL MARCINEK, MAREK RICHTER, JINDRICH SPINAR, JIRI MATUSKA, MARTIN TESAK, ZUZANA MOTOVSKA, MARIAN BRANNY, JIRI MALY, MARTIN MALY, MARTIN WIENDL, LENKA FOLTYNOVA CAISOVA, JOSEF SLABY, PETR VOJTISEK, JAN PIRK, LENKA SPINAROVA, MIROSLAVA BENESOVA, JULIA CANADYOVA, MIROSLAV HOMZA, JINDRICH FLORIAN, ROSTISLAV POLASEK, ZDENEK COUFAL, VLADIMIRA SKALNIKOVA, RADIM BRAT, MIROSLAV BRTKO, PETR JANSKY, JAROSLAV LINDNER, PAVEL MARCIAN, ZBYNEK STRAKA, MARTIN TRETINA, YAN CARLOS DUARTE, FREDDY POW CHON LONG, MAYRA SANCHEZ, JOSE LOPEZ, CARMITA PERUGACHI, RICARDO MARMOL, FREDDY TRUJILLO, PABLO TERAN, JAAKKO TUOMILEHTO, HENRI TUOMILEHTO, MARJA-LEENA TUOMINEN, ILKKA KANTOLA, GABRIEL STEG, VICTOR ABOYANS, FLORENCE LECLERCQ, EMILE FERRARI, FRANCK BOCCARA, EMMANUEL MESSAS, PATRICK MISMETTI, MARIE ANTOINETTE SEVESTRE, GUILLAUME CAYLA, PASCAL MOTREFF, STEFAN STOERK, HANS-DIRK DUENGEN, CHRISTOPH STELLBRINK, OSMAN GUEROCAK, CHRISTOPH KADEL, RUEDIGER BRAUN-DULLAEUS, MICHAEL JESERICH, CHRISTIAN OPITZ, HANS-FRIEDRICH VOEHRINGER, KARL-FRIEDRICH APPEL, BERNHARD WINKELMANN, THOMAS DORSEL, SIGRID NIKOL, HARALD DARIUS, JURGEN RANFT, SEBASTIAN SCHELLONG, WOLFGANG JUNGMAIR, PIROZE DAVIERWALA, MARC VORPAHL, LASZLO BAJNOK, ZOLTAN LASZLO, EBRAHIM NOORI, GABOR VERESS, ANDRAS VERTES, ANDRAS ZSARY, ERNO KIS, LASZLO KORANYI, JUDIT BAKAI, ZOLTAN BODA, FERENC POOR, ZOLTAN JARAI, VENDEL KEMENY, JOHN BARTON, BRENDAN MCADAM, ANDREW MURPHY, PETER CREAN, NIALL MAHON, RONAN CURTIN, BRIAIN MACNEILL, SEAN DINNEEN, MAJDI HALABI, REUVEN ZIMLICHMAN, DAVID ZELTSER, YOAV TURGEMAN, ELIEZER KLAINMAN, BASIL LEWIS, AMOS KATZ, SHAUL ATAR, EUGENIA NIKOLSKY, STEFANO BOSI, MONICA NALDI, POMPILIO FAGGIANO, DEBORA ROBBA, LUCIO MOS, GIANFRANCO SINAGRA, FRANCO COSMI, LUIGI OLTRONA VISCONTI, DE MATTEIS CARMINE, GIUSEPPE DI PASQUALE, MATTEO DI BIASE, SARA MANDORLA, MARINO BERNARDINANGELI, GIOVANNI CARLO PICCINNI, MICHELE MASSIMO GULIZIA, MARCELLO GALVANI, FLAVIO VENTURI, GIORGIO MOROCUTTI, MARIA GRAZIA BALDIN, CARLO OLIVIERI, GIAN PIERO PERNA, VINCENZO CIRRINCIONE, TAKAYASU KANNO, HIROYUKI DAIDA, YUKIO OZAKI, NAOMASA MIYAMOTO, SHINICHI HIGASHIUE, HIROSHI DOMAE, SHINOBU HOSOKAWA, HIROO KOBAYASHI, TAKEHIKO KURAMOCHI, KENSHI FUJII, KAZUAKI MIZUTOMI, KEIJIRO SAKU, KAZUO KIMURA, YOSHIHARU HIGUCHI, MITSUNORI ABE, HARUHITO OKUDA, TOSHIYUKI NODA, TERUAKI MITA, ATSUSHI HIRAYAMA, HARUHIKO ONAKA, MORIAKI INOKO, MITSUGU HIROKAMI, MUNENORI OKUBO, YUTAKA AKATSUKA, MIZUHO IMAMAKI, HARUO KAMIYA, MAMORU MANITA, TOSHIHARU HIMI, HIDEKI UENO, YUJI HISAMATSU, JUNYA AKO, YASUHIRO NISHINO, HIDEO KAWAKAMI, YUTAKA YAMADA, YUKIHIRO KORETSUNE, TAKAHISA YAMADA, TETSURO YOSHIDA, HIDEKI SHIMOMURA, NORIYUKI KINOSHITA, AKIHIKO TAKAHASHI, KHALID YUSOFF, WAN AZMAN WAN AHMAD, MUHAMMAD RADZI ABU HASSAN, SAZZLI KASIM, AIZAI AZAN ABDUL RAHIM, DIMON MOHD ZAMRIN, MASAHARU MACHIDA, YORIHIKO HIGASHINO, NORIAKI UTSU, AKIHIKO NAKANO, SHIGERU NAKAMURA, TETSUO HASHIMOTO, KENJI ANDO, TOMOHIRO SAKAMOTO, F.J. PRINS, DIRK LOK, JOHANNES GERT-JAN MILHOUS, ERIC VIERGEVER, FRANK WILLEMS, HENK SWART, MARCO ALINGS, ROB BREEDVELD, KEES-JAN DE VRIES, ROGER VAN DER BORGH, FANNY OEI, STIENEKE ZOET-NUGTEREN, HANS KRAGTEN, JEAN PAUL HERRMAN, PAUL VAN BERGEN, MARCEL GOSSELINK, EDUARD HOEKSTRA, ERWIN ZEGERS, EELKO RONNER, FRANK DEN HARTOG, GERARD BARTELS, PETER NIEROP, COEN VAN DER ZWAAN, JACOB VAN ECK, EDWIN VAN GORSELEN, BJORN GROENEMEIJER, PIETER HOOGSLAG, MARC ROBERT DE GROOT, ALDRIN LOYOLA, DENNIS JOSE SULIT, NANNETTE REY, MARIA TERESA ABOLA, DANTE MORALES, ELLEN PALOMARES, MARC EVANS ABAT, GREGORIO ROGELIO, PHILIP CHUA, JOSE CARLO DEL PILAR, JOHN DENNIS ALCARAZ, GERALDINE EBO, LOUIE TIRADOR, JOSEFINA CRUZ, JOHN ANONUEVO, ARTHUR PITARGUE, MARIANNA JANION, TOMASZ GUZIK, GRZEGORZ GAJOS, MACIEJ ZABOWKA, ANDRZEJ RYNKIEWICZ, MARLENA BRONCEL, ANDRZEJ SZUBA, DANUTA CZARNECKA, PAWEL MAGA, IRINA STRAZHESKO, YURY VASYUK, ZHANNA SIZOVA, YURY POZDNYAKOV, OLGA BARBARASH, MIKHAIL VOEVODA, TATIANA POPONINA, ALEXEY REPIN, IRINA OSIPOVA, ANNA EFREMUSHKINA, NINA NOVIKOVA, OLEG AVERKOV, DMITRY ZATEYSHCHIKOV, ARKADIY VERTKIN, AZA AUSHEVA, PATRICK COMMERFORD, SAADIYA SEEDAT, LOUIS VAN ZYL, JAN ENGELBRECHT, ELLEN MAKONLI MAKOTOKO, CATHARINA ELIZABETH PRETORIUS, ZAID MOHAMED, ADRIAN HORAK, THOMAS MABIN, ERIC KLUG, JANG-HO BAE, CHEOLHO KIM, CHONG-JIN KIM, DONG-SOO KIM, YONG JIN KIM, SEUNGJAE JOO, JONG-WON HA, CHUL SOO PARK, JANG YOUNG KIM, YOUNG-KWON KIM, CHRISTINA JARNERT, THOMAS MOOE, MIKAEL DELLBORG, INGEMAR TORSTENSSON, PER ALBERTSSON, LARS JOHANSSON, FARIS AL-KHALILI, HENRIK ALMROTH, TOMMY ANDERSSON, EMIL PANTEV, BENGT-OLOV TENGMARK, BO LIU, GUNDARS RASMANIS, CARL-MAGNUS WAHLGREN, TIZIANO MOCCETTI, ALEXANDER PARKHOMENKO, VIRA TSELUYKO, VOLODYMYR VOLKOV, OLENA KOVAL, LYUDMYLA KONONENKO, OLEKSANDR PROKHOROV, VALERIY VDOVYCHENKO, ANDRIY BAZYLEVYCH, LEONID RUDENKO, VADYM VIZIR, OLEKSANDR KARPENKO, YAROSLAV MALYNOVSKY, VALENTYNA KOVAL, BORYS STOROZHUK, JAMES COTTON, ASOK VENKATARAMAN, ANDREW MORIARTY, DEREK CONNOLLY, PATRICK DAVEY, ROXY SENIOR, INDERPAUL BIRDI, JOHN CALVERT, PATRICK DONNELLY, JASPER TREVELYAN, JUSTIN CARTER, AARON PEACE, DAVID AUSTIN, NEVILLE KUKREJA, THOMAS HILTON, SUNNY SRIVASTAVA, RONALD WALSH, RONALD FIELDS, JOSEPH HAKAS, EDWARD PORTNAY, HARINDER GOGIA, ABRAHAM SALACATA, JOHN J. HUNTER, J MICHAEL BACHARACH, NICOLAS SHAMMAS, DAMODHAR SURESH, RICKY SCHNEIDER, PAUL GURBEL, SUBHASH BANERJEE, PAUL GRENA, NOEL BEDWELL, STEPHEN SLOAN, STEVEN LUPOVITCH, ANAND SONI, KATHLEEN GIBSON, RENEE SANGRIGOLI, RAJENDRA MEHTA, PETER I-HSUAN TSAI, EVE GILLESPIE, STEPHEN DEMPSEY, GLENN HAMROFF, ROBERT BLACK, ELLIS LADER, JOHN B. KOSTIS, VERA BITTNER, WILLIAM MCGUINN, KELLEY BRANCH, VINAY MALHOTRA, STEPHEN MICHAELSON, MICHAEL VACANTE, MATTHEW MCCORMICK, RALUCA ARIMIE, ALAN CAMP, GEORGE DAGHER, N. MATHEW KOSHY, STEPHEN THEW, FREDERICK COSTELLO, MARK HEIMAN, ROBERT CHILTON, MICHAEL MORAN, FREDRIC ADLER, ANTHONY COMEROTA, ANDREW SEIWERT, WILLIAM FRENCH, HARVEY SEROTA, ROBERT HARRISON, FAISAL BAKAEEN, SHUAB OMER, LOKESH CHANDRA, ALAN WHELAN, ANDREW BOYLE, PHILIP ROBERTS-THOMSON, JAMES ROGERS, PATRICK CARROLL, DAVID COLQUHOUN, JAMES SHAW, PETER BLOMBERY, JOHN AMERENA, CHRIS HII, ALISTAIR ROYSE, BHUWAN SINGH, JOSEPH SELVANAYAGAM, SHIRLEY JANSEN, WINGCHI LO, CHRISTOPHER HAMMETT, ROHAN POULTER, SESHASAYEE NARASIMHAN, HENRIK WIGGERS, HENRIK NIELSEN, GUNNAR GISLASON, LARS KOBER, KIM HOULIND, VIBEKE BOENELYKKE SOERENSEN, ULRIK DIXEN, JENS REFSGAARD, ELISABETH ZEUTHEN, PETER SOEGAARD, MARIAN HRANAI, LUDOVIT GASPAR, DANIEL PELLA, KATARINA HATALOVA, ERIKA DROZDAKOVA, IOAN COMAN, DOINA DIMULESCU, DRAGOS VINEREANU, MIRCEA CINTEZA, CRINA SINESCU, CATALINA ARSENESCU, IMRE BENEDEK, ELENA BOBESCU, DAN DOBREANU, DAN GAITA, ADRIAN IANCU, ADRIANA ILIESIU, DANIEL LIGHEZAN, LUCIAN PETRESCU, OCTAVIAN PIRVU, IULIA TEODORESCU, DAN TESLOIANU, MARIUS MARCIAN VINTILA, OVIDIU CHIONCEL, Divisions of Cardiology and Thromboembolism McMaster University Hamiton, Population Health Research Institute, McMaster University [Hamilton, Ontario], Service de Chirurgie Thoracique et Vasculaire - Médecine vasculaire [CHU Limoges], CHU Limoges, Neuroépidémiologie Tropicale (NET), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Research Center [Associazione Nazionale Medici Cardiologi Ospedalieri] (ANMCO Research Center), Associazione Nazionale Medici Cardiologi Ospedalieri (ANMCO), Department of Statistics, University of Haifa [Haifa], Cardiology, University and Emergency Hospital, University of Edinburgh, VA Boston Healthcare System, Hamilton General Hospital, Universidad Autonoma de Madrid (UAM), Cardiology Department, Dipartimento di Bioscienze, University of Parma, University of Barcelona, Hospital Clinic Barcelona, Laval University and Hospital Heart and Lung Institute, UVSQ - UFR des sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), University Hospital Brno, Masaryk University, Department of Public Health, Hémostase, bio-ingénierie et remodelage cardiovasculaires (LBPC), Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Galilée, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Pasteur [Nice] (CHU), Service de Cardiologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Université Paris Descartes - Paris 5 (UPD5)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupe de recherche sur la thrombose (GRT (EA 3065)), Université Jean Monnet [Saint-Étienne] (UJM), Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), CHU Gabriel Montpied (CHU), CHU Clermont-Ferrand, Department of Medicine (DEBRECEN - Dpt Medicine), University of Debrecen, University of Trieste, Lab Dev Cell Biol,Bunkyo Ku, The University of Tokyo, The Netherlands Organisation for Applied Scientific Research (TNO), Regional Specialist Hospital in Wroclaw, Research and Development Centre, Kamienskiego, Division of Angiology, Wroclaw Medical University, Sahlgrenska University Hospital/Östra, Cardiocentro Ticino [Lugano], University of Zürich [Zürich] (UZH), Danylo Halytskyi Lviv National Medical University, Department of Cardiology, Sandwell General Hospital, Physiopathologie et thérapie des déficits sensoriels et moteurs, Université Montpellier 2 - Sciences et Techniques (UM2)-IFR76-Institut National de la Santé et de la Recherche Médicale (INSERM), Rigshospitalet [Copenhagen], Université de Médecine Carol Davila, Cardiology Department [Târgu Mureș], University of Medicine and Pharmacy of Târgu Mureș, Institute for Cardiovascular Diseases C.C. Iliescu, Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM), Associazione Nazionale Medici Cardiologi Ospedalieri [Firenze] (ANMCO), University of Parma = Università degli studi di Parma [Parme, Italie], Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), CHU Gabriel Montpied [Clermont-Ferrand], The University of Tokyo (UTokyo), Universität Zürich [Zürich] = University of Zurich (UZH), and Copenhagen University Hospital
Subjects: Carotid Artery Diseases, Male, Myocardial Infarction, MESH: Lower Extremity, 030204 cardiovascular system & hematology, THERAPY, Stroke/epidemiology, MESH: Dose-Response Relationship, Drug, 0302 clinical medicine, Rivaroxaban, prevention, Hemorrhage/chemically induced, MESH: Peripheral Arterial Disease, MESH: Double-Blind Method, guidelines, MESH: Incidence, 030212 general & internal medicine, Cardiovascular Diseases/mortality, risk, RISK, MESH: Aged, MESH: Middle Aged, Incidence, General Medicine, Middle Aged, 3. Good health, Stroke, MESH: Myocardial Infarction, Lower Extremity, Cardiovascular Diseases, MESH: Platelet Aggregation Inhibitors, Factor Xa Inhibitors/administration & dosage, Drug Therapy, Combination, Female, MESH: Factor Xa Inhibitors, OUTPATIENTS, MESH: Rivaroxaban, management, MESH: Hemorrhage, metaanalysis, Lower Extremity/blood supply, Rivaroxaban/administration & dosage, Hemorrhage, MESH: Drug Administration Schedule, Amputation, Surgical, Drug Administration Schedule, MESH: Stroke, Peripheral Arterial Disease, 03 medical and health sciences, Double-Blind Method, atherothrombosis, Myocardial Infarction/epidemiology, MANAGEMENT, Humans, MESH: Amputation, MESH: Aspirin, Aspirin/administration & dosage, Platelet Aggregation Inhibitors/administration & dosage, METAANALYSIS, Aged, MESH: Humans, Aspirin, Dose-Response Relationship, Drug, MESH: Carotid Artery Diseases, MORTALITY, MESH: Cardiovascular Diseases, cardiovascular event rates, PREVENTION, CARDIOVASCULAR EVENT RATES, MESH: Male, outpatients, atrial-fibrillation, MESH: Drug Therapy, Combination, MESH: Morbidity, Carotid Artery Diseases/complications, lower-extremity amputation, Peripheral Arterial Disease/complications, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Morbidity, MESH: Female, Platelet Aggregation Inhibitors, Amputation/statistics & numerical data, Factor Xa Inhibitors
Abstract: BACKGROUND: Patients with peripheral artery disease have an increased risk of cardiovascular morbidity and mortality. Antiplatelet agents are widely used to reduce these complications.METHODS: This was a multicentre, double-blind, randomised placebo-controlled trial for which patients were recruited at 602 hospitals, clinics, or community practices from 33 countries across six continents. Eligible patients had a history of peripheral artery disease of the lower extremities (previous peripheral bypass surgery or angioplasty, limb or foot amputation, intermittent claudication with objective evidence of peripheral artery disease), of the carotid arteries (previous carotid artery revascularisation or asymptomatic carotid artery stenosis of at least 50%), or coronary artery disease with an ankle-brachial index of less than 0·90. After a 30-day run-in period, patients were randomly assigned (1:1:1) to receive oral rivaroxaban (2·5 mg twice a day) plus aspirin (100 mg once a day), rivaroxaban twice a day (5 mg with aspirin placebo once a day), or to aspirin once a day (100 mg and rivaroxaban placebo twice a day). Randomisation was computer generated. Each treatment group was double dummy, and the patient, investigators, and central study staff were masked to treatment allocation. The primary outcome was cardiovascular death, myocardial infarction or stroke; the primary peripheral artery disease outcome was major adverse limb events including major amputation. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants.FINDINGS: Between March 12, 2013, and May 10, 2016, we enrolled 7470 patients with peripheral artery disease from 558 centres. The combination of rivaroxaban plus aspirin compared with aspirin alone reduced the composite endpoint of cardiovascular death, myocardial infarction, or stroke (126 [5%] of 2492 vs 174 [7%] of 2504; hazard ratio [HR] 0·72, 95% CI 0·57-0·90, p=0·0047), and major adverse limb events including major amputation (32 [1%] vs 60 [2%]; HR 0·54 95% CI 0·35-0·82, p=0·0037). Rivaroxaban 5 mg twice a day compared with aspirin alone did not significantly reduce the composite endpoint (149 [6%] of 2474 vs 174 [7%] of 2504; HR 0·86, 95% CI 0·69-1·08, p=0·19), but reduced major adverse limb events including major amputation (40 [2%] vs 60 [2%]; HR 0·67, 95% CI 0·45-1·00, p=0·05). The median duration of treatment was 21 months. The use of the rivaroxaban plus aspirin combination increased major bleeding compared with the aspirin alone group (77 [3%] of 2492 vs 48 [2%] of 2504; HR 1·61, 95% CI 1·12-2·31, p=0·0089), which was mainly gastrointestinal. Similarly, major bleeding occurred in 79 (3%) of 2474 patients with rivaroxaban 5 mg, and in 48 (2%) of 2504 in the aspirin alone group (HR 1·68, 95% CI 1·17-2·40; p=0·0043).INTERPRETATION: Low-dose rivaroxaban taken twice a day plus aspirin once a day reduced major adverse cardiovascular and limb events when compared with aspirin alone. Although major bleeding was increased, fatal or critical organ bleeding was not. This combination therapy represents an important advance in the management of patients with peripheral artery disease. Rivaroxaban alone did not significantly reduce major adverse cardiovascular events compared with asprin alone, but reduced major adverse limb events and increased major bleeding.FUNDING: Bayer AG.
Published: 2018

4. Long-Term Clinical Outcomes According to Previous Manifestations of Atherosclerotic Disease (from the FAST-MI 2010 Registry)

Author: Etienne Puymirat, Nicolas Danchin, Yves Cottin, Nadia Aissaoui, Tabassome Simon, Jean Ferrières, Gilles Lemesle, Francois Schiele, Pierre Coste, Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Université Paris Descartes - Paris 5 (UPD5)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université Lille 2 - Faculté de Médecine, Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Service de Cardiologie [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital cardiologique du Haut Leveque, Université de Bordeaux Ségalen [Bordeaux 2], Département de Cardiologie (Dep Cardio - BESANCON), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de cardiologie [Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], CHU Saint-Antoine [APHP], Université Pierre et Marie Curie - Paris 6 (UPMC), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de cardiologie [CHRU de Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Paris-Centre de Recherche Cardiovasculaire ( PARCC - U970 ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Descartes - Paris 5 ( UPD5 ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Lipides - Nutrition - Cancer [Dijon - U1231] ( LNC ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Département de Cardiologie ( Dep Cardio - BESANCON ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), Épidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps, Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Plateforme de recherche clinique de l'est parisien ( URCEST-CRCEST ), Service de pharmacologie clinique [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Université Pierre et Marie Curie - Paris 6 ( UPMC ), Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps [Toulouse], Université Paul Sabatier - Toulouse 3 ( UPS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paul Sabatier - Toulouse 3 ( UPS ) -CHU Toulouse [Toulouse]-Hôpital de Rangueil, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Faculté de Médecine Henri Warembourg - Université de Lille, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Cardiologie [CHU Toulouse], Pôle Cardiovasculaire et Métabolique [CHU Toulouse], and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: Male, MESH : Atherosclerosis, medicine.medical_treatment, MESH : Mortality, Myocardial Infarction, MESH : Aged, MESH : Prospective Studies, Angiotensin-Converting Enzyme Inhibitors, Coronary Artery Disease, Disease, MESH : Cerebrovascular Disorders, 0302 clinical medicine, Medicine, Longitudinal Studies, Prospective Studies, MESH: Coronary Artery Disease, Myocardial infarction, Coronary Artery Bypass, MESH: Treatment Outcome, Cause of death, Aged, 80 and over, education.field_of_study, MESH: Middle Aged, Hazard ratio, MESH : Platelet Aggregation Inhibitors, Prognosis, MESH: Case-Control Studies, 3. Good health, MESH: Myocardial Infarction, MESH: Angiotensin Receptor Antagonists, MESH : Angiotensin-Converting Enzyme Inhibitors, Cardiology and Cardiovascular Medicine, MESH: Percutaneous Coronary Intervention, MESH : Case-Control Studies, medicine.medical_specialty, MESH : Angiotensin Receptor Antagonists, MESH: Prognosis, 03 medical and health sciences, Percutaneous Coronary Intervention, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Humans, MESH : Middle Aged, MESH : Coronary Artery Disease, MESH : Aged, 80 and over, MESH: Hydroxymethylglutaryl-CoA Reductase Inhibitors, education, MESH: Age Distribution, Aged, MESH: Humans, MESH: Mortality, Proportional hazards model, MESH: Coronary Artery Bypass, MESH : Humans, Case-control study, MESH : Proportional Hazards Models, medicine.disease, MESH : Coronary Artery Bypass, Case-Control Studies, MESH: Female, MESH: Registries, MESH : Age Distribution, 030204 cardiovascular system & hematology, MESH: Atherosclerosis, MESH: Proportional Hazards Models, MESH: Cause of Death, MESH: Aged, 80 and over, MESH : Percutaneous Coronary Intervention, Risk Factors, MESH: Risk Factors, Cause of Death, MESH : Female, Registries, 030212 general & internal medicine, MESH: Longitudinal Studies, MESH : Longitudinal Studies, MESH: Aged, MESH : Prognosis, MESH: Angiotensin-Converting Enzyme Inhibitors, MESH: Adrenergic beta-Antagonists, Middle Aged, [ SDV.MHEP.CSC ] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, MESH : Risk Factors, Treatment Outcome, MESH: Platelet Aggregation Inhibitors, Cardiology, Female, MESH: Cerebrovascular Disorders, France, MESH : Male, Adrenergic beta-Antagonists, MESH : Adrenergic beta-Antagonists, Population, MESH : Treatment Outcome, MESH: Multivariate Analysis, Angiotensin Receptor Antagonists, Age Distribution, Internal medicine, Mortality, MESH : France, Proportional Hazards Models, MESH : Cause of Death, business.industry, MESH : Hydroxymethylglutaryl-CoA Reductase Inhibitors, MESH : Multivariate Analysis, Percutaneous coronary intervention, Atherosclerosis, MESH: Male, MESH: Prospective Studies, MESH: France, Cerebrovascular Disorders, Multivariate Analysis, Hydroxymethylglutaryl-CoA Reductase Inhibitors, MESH : Myocardial Infarction, business, Platelet Aggregation Inhibitors, MESH : Registries
Abstract: IF 3.398; International audience; The prognosis of patients with acute myocardial infarction (AMI) has notably improved in the past 20 years. Using the French Registry of ST-Elevation and Non-ST-elevation Myocardial Infarction (FAST-MI) 2010 registry, we investigated whether previous manifestations of atherosclerotic disease (i.e., previous MI, or a history of any form of atherosclerotic disease) are at truly increased risk compared with those in whom AMI is the first manifestation of the disease. FAST-MI 2010 is a nationwide French registry including 3,079 patients with AMI, among whom 1,062 patients had a history of cardiovascular atherosclerotic disease and 498 patients had a history of MI. Overall, patients with a history of atherosclerotic disease (or MI) were older compared with patients without known cardiovascular disease (71 ± 13 vs 63 ± 14 years) and had higher cardiovascular risk profiles and co-morbidities. Using fully adjusted Cox multivariate analysis, previous manifestations of atherosclerotic disease were associated with higher 3-year mortality (hazard ratio 1.80, 95% confidence interval 1.40 to 2.31; p
Published: 2017

5. Clinical validation of S100B in the management of a mild traumatic brain injury: issues from an interventional cohort of 1449 adult patients

Author: Vincent Sapin, Damien Bouvier, Jeannot Schmidt, Daniel Pic, Jean Roubin, Farès Moustafa, Gautier Allouchery, Bruno Pereira, Julien Raconnat, Département des Urgences, CHU Clermont-Ferrand, Unité de soins intensifs [Clermont Ferrand], CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], Laboratoire de Biochimie, Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), service de Biostatistiques, DRCI, Centre Hospitalier Universitaire de Clermont-Ferrand, Génétique, Reproduction et Développement (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), and Université Clermont Auvergne [2017-2020] (UCA [2017-2020])
Subjects: genetic structures, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Clinical Biochemistry, S100B, Cohort Studies, 0302 clinical medicine, Risk Factors, MESH: Risk Factors, Medicine, Prospective Studies, Prospective cohort study, MESH: Cohort Studies, MESH: Aged, MESH: Middle Aged, Age Factors, Retrograde amnesia, General Medicine, Middle Aged, 3. Good health, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], MESH: Platelet Aggregation Inhibitors, MESH: Young Adult, Cohort, Medium Risk, Adult, medicine.medical_specialty, Adolescent, Alcohol Drinking, Traumatic brain injury, S100 Calcium Binding Protein beta Subunit, Sensitivity and Specificity, 03 medical and health sciences, Young Adult, mTBI, Internal medicine, mild traumatic brain injury, Humans, In patient, Aged, MESH: Adolescent, MESH: Age Factors, MESH: Humans, Adult patients, business.industry, MESH: S100 Calcium Binding Protein beta Subunit, Biochemistry (medical), Significant difference, 030208 emergency & critical care medicine, MESH: Adult, medicine.disease, eye diseases, MESH: Prospective Studies, MESH: Sensitivity and Specificity, Brain Injuries, MESH: Brain Injuries, MESH: Biomarkers, sense organs, business, 030217 neurology & neurosurgery, Biomarkers, Platelet Aggregation Inhibitors, MESH: Alcohol Drinking
Abstract: Background: This study’s primary objective was to validate the routine use of S100B via a prospective study. The aim was a reduction of cranial computed tomography (CCT) scans by 30%. The secondary goal was to investigate the influence of age and associated risk factors on the reduction of CCT. Methods: S100B (sampling within 3 h postinjury) was used for patients with mild traumatic brain injury (mTBIs) presenting a medium risk of complications and requiring a CCT scan. Patients with negative S100B (S100B−) were discharged without a CCT scan. Results: Of the 1449 patients included in this study, 468 (32.3%) had S100B− with a sensitivity of 96.4% (95% CI: 87.5%–99.6%), a specificity of 33.4% (95% CI: 31%–36%) and a negative predictive value of 99.6% (95% CI: 98.5%–99.9%). No significant difference in serum levels or the S100B+ rate was observed if patients had retrograde amnesia (0.16 μg/L; 63.8%), loss of consciousness (0.13; 63.6%) or antiplatelet therapy (0.20; 77.9%). Significant differences were found between the S100B concentrations and S100B positivity rates in patients >65 years old and all the groups with patients 65 years old (n=504). Conclusions: The clinical use of S100B in mTBI management reduces the use of CCTs by approximately one-third; furthermore, the percentage of CCTs reduction is influenced by the age of the patient.
Published: 2018

6. Clinical Impact of Pharmacogenomics of Clopidogrel in Stroke

Author: Nicolas Danchin, Tabassome Simon, Centre de Ressources Biologiques HUEP-UPMC (CRB HUEP-UPMC), UMS omique (OMIQUE), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Platelet Aggregation, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, Pharmacology, MESH: Genotype, 0302 clinical medicine, P2Y12, 030212 general & internal medicine, Stroke, ComputingMilieux_MISCELLANEOUS, pharmacogenetics, MESH: Platelet Aggregation, MESH: Treatment Outcome, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Clopidogrel, stroke, 3. Good health, Treatment Outcome, MESH: Platelet Aggregation Inhibitors, Platelet aggregation inhibitor, Cardiology and Cardiovascular Medicine, medicine.drug, medicine.medical_specialty, Ticlopidine, Genotype, MESH: Ticlopidine, MESH: Pharmacogenetics, Boxed warning, CYP2C19, MESH: Stroke, 03 medical and health sciences, Physiology (medical), Internal medicine, medicine, Humans, cardiovascular diseases, platelet aggregation inhibitors, thrombosis, outcome assessment (health care), MESH: Humans, business.industry, MESH: Clopidogrel, Editorials, medicine.disease, Cytochrome P-450 CYP2C19, MESH: Cytochrome P-450 CYP2C19, Pharmacogenomics, business, Pharmacogenetics
Abstract: Article, see p 21 Despite progress in the diagnosis and treatment of stroke, it is estimated that >900 000 patients each year in the United States have a new stroke or transient ischemic attack (TIA) with an annual risk of 3% to 4% for recurrent events.1 The incidence of stroke or TIA is even higher in some countries such as China.2 Preventing stroke is therefore a major worldwide public health issue. Clopidogrel, in addition to 3 weeks of aspirin therapy, has been effective in reducing the risk of recurrence at 3 months in Chinese patients with TIA or a minor acute ischemic stroke, mainly by reducing the risk of recurrent ischemic stroke.3 To become active, clopidogrel needs to be metabolized via a 2-step oxidation process involving several hepatic cytochrome P450 isoenzymes, notably CYP2C19 , and irreversibly binds to P2Y12 receptors.4 Conversion of clopidogrel to its active metabolite depends on CYP2C19 genetic polymorphisms, with decreased platelet inhibition in carriers of 1 or 2 loss-of-function alleles (ie, intermediate or poor metabolizers). Several studies have shown that in patients with acute coronary syndromes treated by clopidogrel, carriers of at least 1 CYP2C19 loss-of-function allele, notably CYP2C19*2 , were at increased risk of major cardiovascular events and stent thrombosis, with a gene-dose relationship.5–8 Conversely, the CYP2C19*17 variant allele has been related to enhanced levels of active clopidogrel metabolites, greater inhibition of ADP-induced platelet aggregation, and increased risk of bleeding without an impact on ischemic events.9 The US Food and Drug Administration boxed warning in 2010 stated that CYP2C19 genotyping can be used as an aid in assessing the therapeutic safety and for considering alternative strategies to CYP2C19 poor metabolizers. From a clinical standpoint, however, the added value of assessing CYP2C19 polymorphisms depends on 3 factors: the …
Published: 2017

7. Prévalence et facteurs associés à la prescription sous-optimale des anti-thrombotiques selon les critères STOPP/START chez le sujet âgé en médecine générale. Étude observationnelle multicentrique en pharmacie d’officine

Author: Dubois-Puechlong, Ségolène, Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), and Dominique Bonnet-Zamponi
Subjects: Prescription médicamenteuse sous-optimale, MESH: Aged, Analyse de prescription, Aged 75 and over, Anti-thrombotics, Prescription drug misuse, Anti-vitamine K, Anti-coagulant oral direct, Prescription médicamenteuse inappropriée, MESH: Inappropriate Prescribing, Anti-aggrégant plaquettaire, MESH: Platelet Aggregation Inhibitors, Outil STOPP/START, Anti-thrombotique, Sujets âgés de 75 ans et plus, MESH: Fibrinolytic Agents, MESH: Potentially Inappropriate Medication List, Drug utilization review, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, STOPP/START criteria
Abstract: Objective: to assess the prevalence of inappropriate prescribing of antithrombotic therapy (AT) in older outpatients and to examine the associated factors. DESIGN: multicenter prospective study. Setting: 75 pharmacies in 11 French départements. Participants: 1178 patients aged =75 years coming to community pharmacy with prescription from general practitioners (GP) (48.8% female, mean age 82.8; 94% in Paris and surroundings). Data collection: 75 pharmacy trainee students collected data from patients structured interview and GP’s prescription into an electronic case report. Measurements: Updated 2014 STOPP/START criteria regarding AT were applied to each prescription. Factors associated with =1 STOPP-AT criteria and with =1 START-AT criteria were studied (uni and multivariate analyses). Results: –20% prescriptions had =1 STOPP-AT criteria and 12% =1 START-AT criteria. The most frequent STOPP and START-AT criteria were respectively AT prescribing despite a concurrent significant bleeding risk and omission of AT in chronic atrial fibrillation. Two factors were associated with =1 STOPP-AT criteria: the number of medications ([5-7[ OR 5.63 IC[1.66-19.08]; =10 OR 24.33 IC[7.55-78.38] p=10 OR 24,33 IC[7,55-78,38] p
Published: 2016

8. Antibody-Dependent NK Cell Activation Is Associated with Late Kidney Allograft Dysfunction and the Complement-Independent Alloreactive Potential of Donor-Specific Antibodies

Author: Tristan Legris, Christophe Picard, Dilyana Todorova, Luc Lyonnet, Cathy Laporte, Chloe Dumoulin, Corinne Nicolino-Brunet, Laurent Daniel, Anderson Loundou, Sophie Morange, Stanislas Bataille, Henri Vacher Coponat, Valerie Moal, Yvon Berland, Francoise Dignat George, Stephane Burtey, Pascale Paul, Centre de néphrologie et transplantation rénale [Hôpital de la Conception - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Anthropologie bio-culturelle, Droit, Ethique et Santé (ADES), Aix Marseille Université (AMU)-EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique (CNRS), Etablissement Français du Sang - Alpes-Méditerranée (EFS - Alpes-Méditerranée), Etablissement Français du Sang, Vascular research center of Marseille (VRCM), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie de l'Endothelium, Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Laboratoire d'anatomie, pathologie, neuropathologie, Hôpital de la Timone [CHU - APHM] (TIMONE), Unité d'Aide Méthodologique, Assistance Publique - Hôpitaux de Marseille (APHM)-CHU Marseille, CIC - Biotherapie - Marseille, Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Immunologie [Hôpital de la Conception - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION)-Centre National de la Recherche Scientifique (CNRS), This work was in part supported by translational research grants funded by the Assistance Publique des Hôpitaux de Marseille, Institut National de la Santé et de la Recherche Médicale, L’Institut National Du Cancer (INCa), and Direction Générale de l’Offre de Soins (DGOS) (Acronym FEG CO8-17, ID 2008-A00604-51, AORC MAT, Microangiopathies Thrombotiques, principal investigator: Pr G. Kaplanski). CL was supported by SATT (South East Accelerating Technology Transfer)., Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), and DIGNAT-GEORGE, Françoise
Subjects: 0301 basic medicine, lcsh:Immunologic diseases. Allergy, [SDV]Life Sciences [q-bio], Immunology, kidney transplantation, 030230 surgery, MESH: Anticoagulants, Antibody mediated rejection, donor-specific antibodies, MESH: Venous Thromboembolism, 03 medical and health sciences, Interleukin 21, 0302 clinical medicine, MESH: Risk Factors, MESH: Cell-Derived Microparticles, medicine, Immunology and Allergy, Cytotoxic T cell, MESH: Animals, MESH: Neoplasms, MESH: Thrombosis, Kidney transplantation, Original Research, Antibody-dependent cell-mediated cytotoxicity, Lymphokine-activated killer cell, natural killer cells, MESH: Humans, biology, MESH: Thromboplastin, natural killer (NK) cells, medicine.disease, MESH: Neoplasm Metastasis, 3. Good health, [SDV] Life Sciences [q-bio], Transplantation, 030104 developmental biology, MESH: Platelet Aggregation Inhibitors, MESH: Blood Coagulation, biology.protein, Interleukin 12, antibody-mediated rejection, MESH: Disease Progression, Antibody, MESH: Disease Models, Animal, lcsh:RC581-607, antibody-dependent cellular cytotoxicity
Abstract: International audience; Although kidney transplantation remains the best treatment for end-stage renal failure, it is limited by chronic humoral aggression of the graft vasculature by donor-specific antibodies (DSAs). The complement-independent mechanisms that lead to the antibody-mediated rejection (ABMR) of kidney allografts remain poorly understood. Increasing lines of evidence have revealed the relevance of natural killer (NK) cells as innate immune effectors of antibody-dependent cellular cytotoxicity (ADCC), but few studies have investigated their alloreactive potential in the context of solid organ transplantation. Our study aimed to investigate the potential contribution of the antibody-dependent alloreactive function of NK cells to kidney graft dysfunction. We first conducted an observational study to investigate whether the cytotoxic function of NK cells is associated with chronic allograft dysfunction. The NK-Cellular Humoral Activation Test (NK-CHAT) was designed to evaluate the recipient and antibody-dependent reactivity of NK cells against allogeneic target cells. The release of CD107a/Lamp1(+) cytotoxic granules, resulting from the recognition of rituximab-coated B cells by NK cells, was analyzed in 148 kidney transplant recipients (KTRs, mean graft duration: 6.2 years). Enhanced ADCC responsiveness was associated with reduced graft function and identified as an independent risk factor predicting a decline in the estimated glomerular filtration rate over a 1-year period (hazard ratio: 2.83). In a second approach, we used the NK-CHAT to reveal the cytotoxic potential of circulating alloantibodies in vitro. The level of CD16 engagement resulting from the in vitro recognition of serum-coated allogeneic B cells or splenic cells was further identified as a specific marker of DSA-induced ADCC. The NK-CHAT scoring of sera obtained from 40 patients at the time of transplant biopsy was associated with ABMR diagnosis. Our findings indicate that despite the administration of immunosuppressive treatments, robust ADCC responsiveness can be maintained in some KTRs. Because it evaluates both the Fab recognition of alloantigens and Fc-driven NK cell activation, the NK-CHAT represents a potentially valuable tool for the non-invasive and individualized evaluation of humoral risk during transplantation.
Published: 2016

9. Antiplatelet and oral anticoagulant therapies in chronic hemodialysis patients: prescribing practices and bleeding risk

Author: Collette, Camille, Clerc-Urmès, Isabelle, Laborde-Castérot, Hervé, Frimat, Luc, Ayav, Carole, Peters, Nicolas, Martin, Alexandre, Agrinier, Nelly, Thilly, Nathalie, Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), CHU Bordeaux [Bordeaux], Service de Néphrologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CIC-Nancy, and Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy]-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, Male, Risk, pharmacoepidemiology, MESH: Probability, MESH: Renal Insufficiency, Chronic, Administration, Oral, Hemorrhage, MESH: Anticoagulants, Cohort Studies, MESH: Proportional Hazards Models, MESH: Aged, 80 and over, prescribing practices, Renal Dialysis, oral anticoagulant, Humans, MESH: Renal Dialysis, Renal Insufficiency, Chronic, MESH: Cohort Studies, Aged, Probability, Proportional Hazards Models, Retrospective Studies, Aged, 80 and over, MESH: Aged, hemodialysis, MESH: Humans, MESH: Middle Aged, MESH: Risk, bleeding events, Anticoagulants, MESH: Adult, MESH: Retrospective Studies, MESH: Follow-Up Studies, Middle Aged, antiplatelet agent, MESH: Male, MESH: Drug Therapy, Combination, MESH: Platelet Aggregation Inhibitors, MESH: Administration, Oral, Drug Therapy, Combination, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Female, Platelet Aggregation Inhibitors, MESH: Hemorrhage, Follow-Up Studies
Abstract: International audience; PURPOSE:Results of previous studies assessing the risk of bleeding associated with prescription of antiplatelet (AP) and/or oral anticoagulant (AC) therapy to hemodialysis patients are conflicting. Our purpose was to describe practices for prescription of AP and AC in hemodialysis patients in the Lorraine region, and to assess their effect on the risk of major bleeding events.METHODS:All adults with chronic kidney disease who began a first renal replacement therapy by hemodialysis in 2009 or 2010 in one of the 12 dialysis centers in Lorraine were included in the Thrombosis and Hemorrhage in HemoDialysis patients (T2HD) study and followed up until 30 June 2013. The association of each treatment (AP, AC, AP + AC) with the risk of major bleeding was estimated by three Cox proportional hazard models with an inverse probability of treatment weighting on a propensity score, considering the untreated patients as the reference.RESULTS:Among 502 patients included, 227 (45.2%) received an AP, 68 (13.5%) an AC, 81 (16.1%) a combination AP + AC, and 126 (25.1%) were untreated. As compared with untreated patients, those given AP (HR 5.52, 95% CI [3.11-9.80]), AC (HR: 4.15, 95% CI: [3.46-4.99]), and AP + AC (HR: 5.59, 95% CI [2.62-11.91]) were at greater risk of major bleeding events.CONCLUSIONS:The risk of major bleeding is higher in patients receiving an oral AC compared with untreated patients and those receiving an AP agent. A combination of the two drugs does not seem to increase the risk.
Published: 2016

10. Aspirin and Extended-Release Dipyridamole versus Clopidogrel for Recurrent Stroke

Author: Sacco, Rl, Diener, Hc, Yusuf, S, Cotton, D, Ounpuu, S, Lawton, Wa, Palesch, Y, Martin, Rh, Albers, Gw, Bath, P, Bornstein, N, Chan, Bp, Chen, St, Cunha, L, Dahlöf, B, DE KEYSER, J, Donnan, Ga, Estol, C, Gorelick, P, Gu, V, Hermansson, K, Hilbrich, L, Kaste, M, Lu, C, Machnig, T, Pais, P, Roberts, R, Skvortsova, V, Teal, P, Toni, Danilo, Vandermaelen, C, Voigt, T, Weber, M, Yoon, Bw, Lembo, Giuseppe, Rasura, Maurizia, Sacchetti, Maria Luisa, Faculteit Medische Wetenschappen/UMCG, Gerontology, Department of neurology, University of Miami Leonard M. Miller School of Medicine (UMMSM)-University of Miami [Coral Gables], Universität Duisburg-Essen [Essen], Boehringer Ingelheim GmbH, Boehringer Ingelheim Pharmaceuticals, Population Health Research Institute, McMaster University [Hamilton, Ontario]-Hamilton General Hospital, Boehringer Ingelheim, Boehringer Ingelheim Ltd, Department of biostatistics, Bioinformatics and Epidemiology, Medical University of South Carolina [Charleston] (MUSC), Neurology and Neurological Sciences, Stanford University, Stroke Trials Unit, University of Nottingham, UK (UON), Neurology Department, Ichilov Medical Center, Division of Neurology, Department of Medicine, National University Hospital Singapore, Department of Neurology, Chang Gung Memorial Hospital [Taipei] (CGMH), Neurology department, Universidade de Coimbra [Coimbra], Institute of Medicine, Sahlgrenska University Hospital [Gothenburg], University Medical Center Groningen [Groningen] (UMCG), National Stroke Research Institute, University of Melbourne, Neurological Center for Treatment and Research, Department of Neurology and Rehabilitation, University of Illinois System, Boehringer Ingelheim Shanghai Pharmaceuticals Co Ltd, Boehringer Ingelheim AB, Helsinki University Central Hospital, Huashan Hospital [Shangai], Saint John's Medical College, Clinical Trials Methodoloy Group, McMaster University [Hamilton, Ontario], Neurology & Neurosurgery Clinic, Russian State Medical University, Department of Medicine, Neurology, Faculty of Medicine, University of British Columbia (UBC), Department of Neurological Sciences, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Cardiology Department, SUNY Downstate Medical Center, State University of New York (SUNY)-State University of New York (SUNY), Seoul National University Hospital, Service de Neurologie [CHU Limoges], CHU Limoges, Neuroépidémiologie Tropicale et Comparée (NETEC), Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Université de Limoges (UNILIM), Université de Limoges (UNILIM)-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Sacco, Rl, Diener, Hc, Yusuf, S, Cotton, D, Ounpuu, S, Lawton, Wa, Palesch, Y, Martin, Rh, Albers, Gw, Bath, P, Bornstein, N, Chan, Bp, Chen, St, Cunha, L, Dahlof, B, DE KEYSER, J, Donnan, Ga, Estol, C, Gorelick, P, Gu, V, Hermansson, K, Hilbrich, L, Kaste, M, Lu, C, Machnig, T, Pais, P, Roberts, R, Skvortsova, V, Teal, P, Toni, D, Vandermaelen, C, Voigt, T, Weberm, Yoon, Bw, and Comi, Giancarlo
Subjects: Male, Myocardial Infarction, Angiotensin-Converting Enzyme Inhibitors, MESH: Cognition, Brain Ischemia, NON-INFERIORITY TRIALS, 0302 clinical medicine, aspirina, Secondary Prevention, Aspirin, MESH: Middle Aged, MESH: Risk, Hazard ratio, MESH: Disability Evaluation, MESH: Brain Ischemia, Dipyridamole, MESH: Follow-Up Studies, ARTERIAL ORIGIN ESPRIT, General Medicine, RANDOMIZED CONTROLLED-TRIAL, 3. Good health, MESH: Myocardial Infarction, Platelet aggregation inhibitor, Drug Therapy, Combination, MESH: Hemorrhage, medicine.medical_specialty, MESH: Ticlopidine, MESH: Delayed-Action Preparations, MESH: Drug Delivery Systems, MESH: Factor Analysis, Statistical, Hemorrhage, MESH: Drug Administration Schedule, MESH: Stroke, 03 medical and health sciences, MESH: Severity of Illness Index, Humans, Vascular Diseases, ACTIVE CONTROLLED-TRIALS, MESH: Kaplan-Meier Estimate, Aged, ictus, trial clinico, MESH: Humans, Proportional hazards model, MESH: Angiotensin II Type 1 Receptor Blockers, MESH: Retrospective Studies, medicine.disease, MESH: Benzoates, PREVENTION, MESH: International Cooperation, Delayed-Action Preparations, Benzimidazoles, Factor Analysis, Statistical, MESH: Mental Status Schedule, MESH: Female, 030217 neurology & neurosurgery, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Benzoates, MESH: Proportional Hazards Models, DOUBLE-BLIND, MESH: Double-Blind Method, Telmisartan, Stroke, MESH: Aged, MESH: Angiotensin-Converting Enzyme Inhibitors, Middle Aged, Clopidogrel, MESH: Platelet Aggregation Inhibitors, Anesthesia, MESH: Vascular Diseases, Cardiology, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.drug, Risk, Double-Blind Method, TICLOPIDINE, Internal medicine, medicine, cardiovascular diseases, MESH: Aspirin, Ticlopidine, HIGH-RISK PATIENTS, Proportional Hazards Models, CEREBRAL-ISCHEMIA, business.industry, MESH: Male, MESH: Recurrence, MESH: Drug Therapy, Combination, TRANSIENT ISCHEMIC ATTACK, MESH: Dipyridamole, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Benzimidazoles, business, Platelet Aggregation Inhibitors
Abstract: Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial; International audience; BACKGROUND: Recurrent stroke is a frequent, disabling event after ischemic stroke. This study compared the efficacy and safety of two antiplatelet regimens--aspirin plus extended-release dipyridamole (ASA-ERDP) versus clopidogrel. METHODS: In this double-blind, 2-by-2 factorial trial, we randomly assigned patients to receive 25 mg of aspirin plus 200 mg of extended-release dipyridamole twice daily or to receive 75 mg of clopidogrel daily. The primary outcome was first recurrence of stroke. The secondary outcome was a composite of stroke, myocardial infarction, or death from vascular causes. Sequential statistical testing of noninferiority (margin of 1.075), followed by superiority testing, was planned. RESULTS: A total of 20,332 patients were followed for a mean of 2.5 years. Recurrent stroke occurred in 916 patients (9.0%) receiving ASA-ERDP and in 898 patients (8.8%) receiving clopidogrel (hazard ratio, 1.01; 95% confidence interval [CI], 0.92 to 1.11). The secondary outcome occurred in 1333 patients (13.1%) in each group (hazard ratio for ASA-ERDP, 0.99; 95% CI, 0.92 to 1.07). There were more major hemorrhagic events among ASA-ERDP recipients (419 [4.1%]) than among clopidogrel recipients (365 [3.6%]) (hazard ratio, 1.15; 95% CI, 1.00 to 1.32), including intracranial hemorrhage (hazard ratio, 1.42; 95% CI, 1.11 to 1.83). The net risk of recurrent stroke or major hemorrhagic event was similar in the two groups (1194 ASA-ERDP recipients [11.7%], vs. 1156 clopidogrel recipients [11.4%]; hazard ratio, 1.03; 95% CI, 0.95 to 1.11). CONCLUSIONS: The trial did not meet the predefined criteria for noninferiority but showed similar rates of recurrent stroke with ASA-ERDP and with clopidogrel. There is no evidence that either of the two treatments was superior to the other in the prevention of recurrent stroke. (ClinicalTrials.gov number, NCT00153062.)
Published: 2008

11. Resistance to platelet antiaggregants: an important cause of very late thrombosis of drug eluting stents? Observations from five cases

Author: J. Machecourt, Bernard Bertrand, G. Barone-Rochette, O. Ormezzano, Gérald Vanzetto, B. Polack, Clinique Cardiologie et Hypertension Artérielle, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon, Radiopharmaceutiques Biocliniques, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), TheREx, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), and VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)
Subjects: Male, MESH: Coronary Thrombosis, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Platelet Aggregation, medicine.medical_treatment, Drug Resistance, Thrombose très tardive, MESH: Flow Cytometry, 030204 cardiovascular system & hematology, Résistanceau clopidogrel, Very late thrombosis, MESH: Aged, 80 and over, 0302 clinical medicine, MESH: Fibrinolytic Agents, Platelet, Prospective Studies, 030212 general & internal medicine, Phosphorylation, [INFO.INFO-BT]Computer Science [cs]/Biotechnology, Prospective cohort study, Resistance to aspirin, MESH: Platelet Aggregation, Aged, 80 and over, MESH: Aged, Aspirin, MESH: Middle Aged, Microfilament Proteins, Stent actif, Drug-Eluting Stents, MESH: Platelet Function Tests, General Medicine, Middle Aged, Flow Cytometry, Résistance à l’aspirine, Clopidogrel, Thrombosis, 3. Good health, MESH: Platelet Aggregation Inhibitors, Drug-eluting stent, Anesthesia, MESH: Cell Adhesion Molecules, MESH: Drug Resistance, Cardiology, Female, Cardiology and Cardiovascular Medicine, MESH: Drug-Eluting Stents, medicine.drug, medicine.medical_specialty, Ticlopidine, Platelet Function Tests, MESH: Ticlopidine, Active stent, MESH: Phosphoproteins, MESH: Microfilament Proteins, 03 medical and health sciences, Fibrinolytic Agents, Internal medicine, medicine, Humans, MESH: Aspirin, Aged, MESH: Humans, MESH: Phosphorylation, Vascular disease, business.industry, Coronary Thrombosis, Phosphoproteins, medicine.disease, MESH: Male, MESH: Prospective Studies, Resistance to clopidogrel, Complication, business, Cell Adhesion Molecules, MESH: Female, Platelet Aggregation Inhibitors
Abstract: International audience; BACKGROUND: Very late thrombosis of drug eluting stents is a rare complication that might be triggered by resistance to platelet antiaggregants (PAAs). AIM: Following an initial case where clinical data strongly suggested resistance to PAAs, we carried out a prospective systematic analysis of platelet aggregation in four subsequent cases of late thrombosis. METHODS: Resistance to aspirin was investigated with the PFA-100 test employing a collagen-epinephrine cartridge (Platelet Function Analyzer; Dade Behring). Resistance to clopidogrel was determined by flow cytometry of intraplatelet vasodilator-stimulated phosphoprotein (VASP) phosphorylation. RESULTS: All four cases showed resistance to either aspirin or clopidogrel, and two cases showed dual resistance to both of these PAAs. CONCLUSION: Analysis of platelet function in a patient with late stent thrombosis is useful and may allow adaptation of subsequent patient management. The value of monitoring platelet function after implantation of a drug eluting stent should be evaluated in prospective studies.
Published: 2008
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12. Cerebral Ischemia Probably Related to Isotretinoin

Author: Francisco Macian-Montoro, Jean-Michel Vallat, Louis Merle, Marie-Laure Laroche, Service de Pharmacologie, toxicologie et pharmacovigilance [CHU Limoges], CHU Limoges, Service de Neurologie [CHU Limoges], and Université de Limoges (UNILIM)
Subjects: Adult, Male, medicine.medical_specialty, MESH: Heparin, medicine.drug_class, Ischemia, 030204 cardiovascular system & hematology, Brain Ischemia, Central nervous system disease, Brain ischemia, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, MESH: Isotretinoin, medicine, Humans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Pharmacology (medical), Retinoid, MESH: Aspirin, Isotretinoin, skin and connective tissue diseases, Acne, MESH: Humans, Aspirin, Heparin, business.industry, Vascular disease, MESH: Brain Ischemia, MESH: Adult, Dipyridamole, medicine.disease, MESH: Male, Facial paralysis, 3. Good health, Surgery, MESH: Dermatologic Agents, MESH: Platelet Aggregation Inhibitors, Anesthesia, MESH: Dipyridamole, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Dermatologic Agents, business, Platelet Aggregation Inhibitors, medicine.drug
Abstract: OBJECTIVE: To report a case of cerebral ischemia in a patient receiving oral isotretinoin for severe acne. CASE SUMMARY: A 30-year-old right-handed man was admitted for left facial paralysis and dysarthria. He had received oral isotretinoin 45 mg/day for 3 months for treatment of severe acne. A cerebral computed tomography scan showed hypodensity in the right middle cerebral territory corresponding to cerebral ischemia. The patient reported having experienced a similar episode 7 years before, after 3 months' treatment with oral isotretinoin. No risk factors were identified. Isotretinoin was discontinued on admission and the disorders resolved. DISCUSSION: Our patient did not present thrombotic risk factors and was not being treated with any drug other than isotretinoin; however, he developed 2 episodes of cerebral ischemia following 2 episodes of oral isotretinoin treatment. According to the Naranjo probability scale, the relationship of cerebral ischemia to administration of isotretinoin was probable. Other reports of thrombotic accidents, as well as some cases of hemorrhage in patients receiving isotretinoin, have been published. This drug seems to act on the coagulation process by a still unexplained mechanism. CONCLUSIONS: Given that isotretinoin is a treatment prescribed most frequently for adolescents and young adults and that cerebral ischemia can produce serious handicaps, an evaluation of vascular risk should be made prior to treatment with this drug.
Published: 2007

13. 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC)

Author: Roffi, Marco, Patrono, Carlo, Collet, Jean-Philippe, Mueller, Christian, Valgimigli, Marco, Andreotti, Felicita, Bax, Jeroen J, Borger, Michael A, Brotons, Carlos, Chew, Derek P, Gencer, Baris, Hasenfuss, Gerd, Kjeldsen, Keld, Lancellotti, Patrizio, Landmesser, Ulf, Mehilli, Julinda, Mukherjee, Debabrata, Storey, Robert F, Windecker, Stephan, Patrono, Marco, Baumgartner, Helmut, Gaemperli, Oliver, Achenbach, Stephan, Agewall, Stefan, Badimon, Lina, Baigent, Colin, Bueno, Héctor, Bugiardini, Raffaele, Carerj, Scipione, Casselman, Filip, Cuisset, Thomas, Erol, Çetin, Fitzsimons, Donna, Halle, Martin, Hamm, Christian, Hildick-Smith, David, Huber, Kurt, Iliodromitis, Efstathios, James, Stefan, Lewis, Basil S, Lip, Gregory y H, Piepoli, Massimo F, Richter, Dimitrios, Rosemann, Thomas, Sechtem, Udo, Steg, Ph Gabriel, Vrints, Christian, Luis Zamorano, Jose, Nutrition, obésité et risque thrombotique (NORT), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Roffi, Marco, Patrono, Carlo, Collet, Jean-Philippe, Mueller, Christian, Valgimigli, Marco, Andreotti, Felicita, Bax, Jeroen J, Borger, Michael A, Brotons, Carlo, Chew, Derek P, Gencer, Bari, Hasenfuss, Gerd, Kjeldsen, Keld, Lancellotti, Patrizio, Landmesser, Ulf, Mehilli, Julinda, Mukherjee, Debabrata, Storey, Robert F, Windecker, Stephan, Baumgartner, Helmut, Gaemperli, Oliver, Achenbach, Stephan, Agewall, Stefan, Badimon, Lina, Baigent, Colin, Bueno, Héctor, Bugiardini, Raffaele, Carerj, Scipione, Casselman, Filip, Cuisset, Thoma, Erol, Çetin, Fitzsimons, Donna, Halle, Martin, Hamm, Christian, Hildick-Smith, David, Huber, Kurt, Iliodromitis, Efstathio, James, Stefan, Lewis, Basil S, Lip, Gregory Y H, Piepoli, Massimo F, Richter, Dimitrio, Rosemann, Thoma, Sechtem, Udo, Steg, Ph Gabriel, Vrints, Christian, Luis Zamorano, Jose, ACS - Amsterdam Cardiovascular Sciences, APH - Amsterdam Public Health, and Cardiology
Subjects: High-sensitivity troponin, Ticagrelor, Chest pain unit, medicine.medical_treatment, Atherothrombosis, Myocardial ischaemia, Recommendations, MESH: Risk Assessment, Early invasive strategy, Electrocardiography, Acute cardiac care, Acute coronary syndromes, Angioplasty, Anticoagulation, Apixaban, Aspirin, Beta-blockers, Bivalirudin, Bypass surgery, Cangrelor, Clopidogrel, Dabigatran, Diabetes, Enoxaparin, European society of cardiology, Fondaparinux, Glycoprotein IIb/IIIa inhibitors, Guidelines, Heparin, Nitrates, Non-ST-elevation myocardial infarction, Platelet inhibition, Prasugrel, Revascularization, Rhythm monitoring, Rivaroxaban, Statin, Stent, Unstable angina, Vorapaxar, Cardiology and Cardiovascular Medicine, ST segment, Myocardial infarction, 610 Medicine & health, ComputingMilieux_MISCELLANEOUS, MESH: Platelet Glycoprotein GPIIb-IIIa Complex, Platelet aggregation inhibitor, MESH: Percutaneous Coronary Intervention, MESH: Hemorrhage, medicine.medical_specialty, Acute coronary syndrome, Cardiotonic Agents, MESH: Algorithms, Hemorrhage, Platelet Glycoprotein GPIIb-IIIa Complex, MESH: Anticoagulants, Risk Assessment, Percutaneous Coronary Intervention, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Humans, Acute Coronary Syndrome, Physical Examination, Management of acute coronary syndrome, MESH: Humans, MESH: Cardiotonic Agents, Recommendation, medicine.disease, MESH: Acute Coronary Syndrome, Long-Term Care, MESH: Coronary Angiography, MESH: Non-ST Elevated Myocardial Infarction, Purinergic P2Y Receptor Antagonists, Human medicine, Biomarkers, Guideline, Diabete, Nitrate, Coronary Angiography, MESH: Angina Pectoris, MESH: Long-Term Care, Non-ST Elevated Myocardial Infarction, reproductive and urinary physiology, Atherothrombosi, MESH: Platelet Aggregation Inhibitors, embryonic structures, Cardiology, MESH: Purinergic P2Y Receptor Antagonists, biological phenomena, cell phenomena, and immunity, Algorithms, medicine.drug, Settore BIO/14 - FARMACOLOGIA, Glycoprotein IIb/IIIa inhibitor, European Society of Cardiology, Angina Pectoris, Diagnosis, Differential, MESH: Physical Examination, MESH: Diagnosis, Differential, Internal medicine, medicine, Beta-blocker, urogenital system, business.industry, Percutaneous coronary intervention, Anticoagulants, MESH: Electrocardiography, MESH: Biomarkers, business, Platelet Aggregation Inhibitors
Abstract: ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation : The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC).
Published: 2015

14. Occlusion of vertebral artery due to transverse canal osteochondroma

Author: Julien Savatovsky, Sandrine Deltour, Didier Dormont, Sarah Fadili, Frédéric Clarençon, François Bonneville, Service de Neuroradiologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Equipe de Recherche Médicale Appliquée (ERMA), Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Université de Limoges (UNILIM)-CHU Limoges, Université Paris 1 Panthéon-Sorbonne (UP1), Service des Urgences Cérébro-Vasculaires [CHU Pitié-Salpétriêre], Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Algorithms, models and methods for images and signals of the human brain (ARAMIS), Inria Paris-Rocquencourt, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP]
Subjects: Osteochondroma, medicine.medical_specialty, MESH: Combined Modality Therapy, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Vertebral artery, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, 030218 nuclear medicine & medical imaging, MESH: Magnetic Resonance Imaging, MESH: Vertebrobasilar Insufficiency, 03 medical and health sciences, MESH: Decompression, Surgical, 0302 clinical medicine, medicine.artery, Occlusion, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Medicine, Radiology, Nuclear Medicine and imaging, Neuroradiology, MESH: Treatment Outcome, MESH: Osteochondroma, MESH: Humans, MESH: Middle Aged, business.industry, [INFO.INFO-CV]Computer Science [cs]/Computer Vision and Pattern Recognition [cs.CV], Anatomy, MESH: Spinal Neoplasms, medicine.disease, Compression (physics), Posterior arch, MESH: Male, Transverse plane, Posterior inferior cerebellar artery, MESH: Platelet Aggregation Inhibitors, [INFO.INFO-TI]Computer Science [cs]/Image Processing [eess.IV], Neurology (clinical), Radiology, business, MESH: Tomography, X-Ray Computed, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, 030217 neurology & neurosurgery
Abstract: International audience; Osteochondroma is a non-rare benign osseous neoplasm[1] that is often observed within the posterior arch of vertebrae.Vascular compression may be observed because of thisexuberant bone formation [2]. Vertebral artery compressionin transverse canal is exceptional. We report on a case ofvertebral artery occlusion related to compressive osteochondroma,responsible for acute stroke in the vertebrobasilarsystem.
Published: 2014

15. Le syndrome des antiphospholipides en néphrologie. Atteinte rénale et aspects pratiques de la prise en charge

Author: Dekeyser, Manon, Zuily, Stéphane, Champigneulle, Jacqueline, Eschwège, Valérie, Frimat, Luc, Perret-Guillaume, Christine, Wahl, Denis, Service de néphrologie-hémodialyse-transplantation [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre régional de compétence des Maladies systémiques et auto-immunes rares de l'adulte et Maladies vasculaires rares, Service d’Anatomie Pathologique [CHRU Nancy], Service d'Hématologie Biologique [CHRU Nancy], Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), Service de Gérontologie [CHRU Nancy], and Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)
Subjects: Biopsy, Renal Veins, MESH: Kidney Transplantation, MESH: Biopsy, Renal Artery, Antiphospholipid syndrome, Thrombophilia, MESH: Renal Dialysis, Traitement, Dialyse, MESH: Middle Aged, MESH: Arterial Occlusive Diseases, Disease Management, Middle Aged, Cardiovascular Diseases, MESH: Platelet Aggregation Inhibitors, MESH: Renal Circulation, Female, Kidney Diseases, Arterial Occlusive Diseases, MESH: Anticoagulants, MESH: Disease Management, MESH: Nervous System Diseases, MESH: Renal Artery, Renal Circulation, Renal Dialysis, MESH: Antiphospholipid Syndrome, Humans, MESH: Thrombosis, MESH: Contraindications, Antihypertensive Agents, MESH: Thrombocytopenia, Transplantation, MESH: Antihypertensive Agents, MESH: Kidney Diseases, MESH: Humans, Thrombotic Microangiopathies, Contraindications, MESH: Thrombotic Microangiopathies, MESH: Thrombophilia, Anticoagulants, MESH: Cardiovascular Diseases, Thrombosis, Kidney Transplantation, Thrombocytopenia, Néphropathie associée au syndrome des antiphospholipides, Treatment, MESH: Renal Veins, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Nervous System Diseases, Dialysis, MESH: Female, Platelet Aggregation Inhibitors, Syndrome des antiphospholipides, Antiphospholipid syndrome nephropathy
Abstract: International audience; The antiphospholipid syndrome is a thrombophilia characterized by the combination of arterial and/or venous thrombotic events or obstetric clinical events, associated with persistent presence of antiphospholipid antibodies. In this syndrome, thromboses may affect all of the vascular tree, renal damage is frequently associated with a specific antiphospholipid syndrome nephropathy. We propose in this review to provide updated recommendations on the management of antiphospholipid syndrome in nephrology. Treatment is based on long-term anticoagulant therapy with or without antiplatelet agents according to clinical events. The use of a conventional nephroprotection must not be forgotten (strict control of blood pressure with drugs blocking the renin-angiotensin-aldosterone system). Catastrophic antiphospholipid syndrome is an extremely severe complication which can threaten the vital prognosis of the patient. This justifies particular surveillance, as well as prevention in high-risk situations. We also illustrate the difficulties of long-term management in these patients, both in dialysis or kidney transplantation.; Le syndrome des antiphospholipides est une thrombophilie caractérisée par l’association d’un événement clinique thrombotique (artériel et/ou veineux) ou obstétrical, associé à la présence durable d’anticorps antiphospholipides. L’atteinte pouvant toucher l’ensemble de l’arbre vasculaire, une atteinte rénale est fréquemment associée avec la description maintenant bien codifiée de la néphropathie associée au syndrome des antiphospholipides. Nous proposons dans cette revue des recommandations actualisées sur la prise en charge du syndrome des antiphospholipides en néphrologie. La thérapeutique se base sur une anticoagulation plus ou moins une antiagrégation à long terme en fonction des événements cliniques sans oublier le recours à une néphroprotection classique (contrôle strict de la pression artérielle avec notamment des thérapeutiques bloquant le système rénine–angiotensine–aldostérone). Le syndrome catastrophique des antiphospholipides est une complication extrêmement grave pouvant mettre en jeu le pronostic vital du patient. Celui-ci justifie une attention toute particulière, ainsi qu’une prévention dans les situations à risque. Nous illustrons également les difficultés de prise en charge au long cours de ces patients, tant en dialyse qu’en transplantation rénale.
Published: 2014

16. Efficacy and safety outcomes of oral anticoagulants and antiplatelet drugs in the secondary prevention of venous thromboembolism: systematic review and network meta-analysis

Author: Marc A. Rodger, George A. Wells, Doug Coyle, Esteban Gandara, Chris Cameron, Marc Carrier, Philip S. Wells, Tammy Clifford, Grégoire Le Gal, Lana A Castellucci, Thrombosis Program, University of Ottawa [Ottawa], Epidemiology and Community Medicine (OTTAWA - ECM), Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Clinical Epidemiology Unit, Ottawa-The Ottawa Hospital, Canadian Agency for Drugs and Technologies in Health (OTTAWA - CADTH), Ottawa, Department of Medicine, Ottawa Hospital, and Calvez, Ghislaine
Subjects: Vitamin K, [SDV]Life Sciences [q-bio], MESH: Calcium Channel Blockers, 030204 cardiovascular system & hematology, MESH: Venous Thromboembolism, 0302 clinical medicine, Rivaroxaban, Recurrence, Medicine, MESH: Animals, 030212 general & internal medicine, MESH: Organ Specificity, Absolute risk reduction, Venous Thromboembolism, General Medicine, MESH: Muscle, Smooth, Vascular, MESH: Thiophenes, Dabigatran, 3. Good health, [SDV] Life Sciences [q-bio], MESH: beta-Alanine, MESH: Platelet Aggregation Inhibitors, Meta-analysis, Anesthesia, MESH: Chemistry, Apixaban, MESH: Cats, MESH: Hemorrhage, medicine.drug, medicine.medical_specialty, MESH: Terminology as Topic, MESH: Rats, Pyridones, Morpholines, MEDLINE, MESH: Morpholines, Hemorrhage, Thiophenes, MESH: Anticoagulants, Placebo, MESH: Nervous System Diseases, 03 medical and health sciences, Internal medicine, MESH: Pyridones, Humans, MESH: Aspirin, MESH: Humans, Aspirin, business.industry, Anticoagulants, MESH: Cardiovascular Diseases, MESH: Vitamin K, MESH: Chemical Phenomena, Odds ratio, MESH: Recurrence, MESH: Heart, beta-Alanine, Pyrazoles, Benzimidazoles, business, MESH: Benzimidazoles, Platelet Aggregation Inhibitors, MESH: Pyrazoles
Abstract: International audience; OBJECTIVE: To summarise and compare the efficacy and safety of various oral anticoagulants (dabigatran, rivaroxaban, apixaban, and vitamin K antagonists) and antiplatelet agents (acetylsalicylic acid) for the secondary prevention of venous thromboembolism. DESIGN: Systematic review and network meta-analysis. DATA SOURCES: Literature search using Medline (1950 to present), Embase (1980 to present), and the Cochrane Register of Controlled Trials using the OVID interface. Publications from potentially relevant journals were also searched by hand. REVIEW METHODS: Randomised controlled trials of patients receiving anticoagulants, antiplatelet drugs, or placebo or observation for secondary prevention of venous thromboembolism. Selected outcomes were rates of recurrent venous thromboembolism and major bleeding. Two reviewers independently extracted data onto standardised forms. RESULTS: 12 articles met our inclusion criteria, with 11,999 patients evaluated for efficacy and 12,167 for safety. All treatments reduced the risk of recurrent venous thromboembolism. Compared with placebo or observation, vitamin K antagonists at a standard adjusted dose (target international normalised ratio 2.0-3.0) showed the highest risk difference (odds ratio 0.07; 95% credible interval 0.03 to 0.15) and acetylsalicylic acid showed the lowest risk difference (0.65; 0.39 to 1.03). Risk of major bleeding was higher with a standard adjusted dose of vitamin K antagonists (5.24; 1.78 to 18.25) than with placebo or observation. Fatal recurrent venous thromboembolism and fatal bleeding were rare. Detailed subgroup and individual patient level data were not available. CONCLUSIONS: All oral anticoagulants and antiplatelet agents investigated in this analysis were associated with a reduced recurrence of venous thromboembolism compared with placebo or observation, although acetylsalicylic acid was associated with the lowest risk reduction. Vitamin K antagonists given at a standard adjusted dose was associated with the greatest risk reduction in recurrent venous thromboembolism, but also the greatest risk of major bleeding.
Published: 2013

17. Vorapaxar in the secondary prevention of atherothrombotic events

Author: Jose Nicolau, Andrzej Rynkiewicz, Keith Fox, Vahid Mansouri, Fausto Miranda Junior, Jose Antônio Marin-Neto, Carlos Tauil, Yves Samson, Giovanni ESPOSITO, David Morrow, Wojciech Sobiczewski, James Spratt, Jacek Kubica, Miguel Urina, STEFANO CARUGO, Majken Karoline Jensen, Frans Van de Werf, Stavros Konstantinides, Oscar Ayo-Martin, Lucia Mazzolai, Isabella TRITTO, ERIC HERNANDEZ-TRIANA, Philip Bath, Diana Gorog, Graeme Hankey, Juhani Airaksinen, Marco Vatrano, Jose Faria Neto, Peter Sinnaeve, Roman Herzig, Serge Timsit, Urszula Fiszer, Attila Csányi, Marcia Chaves, Robert Mikulik, Marek Roik, Mónica Jaramillo, Michel GALINIER, Helle Klingenberg Iversen, Bassem A. Samad, Philippe Gabriel STEG, Elizabeth Coetsee, Guillermo Isasti, Domenico Scrutinio, Silvia Reverté Villarroya, Malcolm Robert Macleod, Michael Lim, Amos Katz, Meyer ELBAZ, Derek Chew, Hanne Christensen, Markus Theurl, Simona Marcheselli, Patricia Simal, Michal Bar, Isabelle Quere, Geert Vanhooren, Piotr Ponikowski, Xavier Garcia-Moll, Elena Corrada, Robert Welsh, Helge Wuttig, Philip Aylward, Carl Magnus Wahlgren, Marco Stramba-Badiale, Fernando Manzur, LAURENT SUISSA, Thierry Moulin, Giancarlo Marenzi, Gian Battista Danzi, Bogumił Ramotowski, Caitrin McDonough, Afanasiev Stanislav, RAUL CARLOS REY, Emilia Solinas, Cardiovascular Division (SZG), Brigham and Women's Hospital [Boston], Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia [Buenos Aires] (FLENI), FLENI, Milpark Hospital (Milpark Hospital), Milpark Hospital, Division of Cardiovascular Research (EDINBURGH - DCVR), University of Edinburgh, Heart Institute (SAO PAULO - Heart Institute), University of São Paulo Medical School, Canisius-Wilhelmina Hospital [Nijmegen, The Netherlands], Instituto de Investigaciones Clinicas Rosario (CIC ROSARIO), CIC ROSARIO, University Hospital Brno, Montreal Heart Institute (MONTREAL HEART INSTITUTE), Service de Neurologie [Brest], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre d'Investigation Clinique (CIC - Brest), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Morrow, DA, Braunwald, E, Bonaca, MP, Ameriso, SF, Dalby, AJ, Fish, MP, Fox, KA, Lipka, LJ, Liu, X, Nicolau, JC, Ophuis, AJ, Paolasso, E, Scirica, BM, Spinar, J, Theroux, P, Wiviott, SD, Strony, J, Murphy, SA, Novo, s, Morrow, Da, Bonaca, Mp, Ameriso, Sf, Dalby, Aj, Fish, Mp, Fox, Kaa, Lipka, Lj, Nicolau, Jc, Ophuis, Ajo, Scirica, Bm, Theroux, P., Wiviott, Sd, Strony, J., Murphy, Sa, Esposito, Giovanni, TRA 2P TIMI 50 Steering Comm, Inves, Diener, Hans Christoph (Beitragende*r), Equipe NEMESIS - Centre de Recherches de l'Institut du Cerveau et de la Moelle épinière (NEMESIS-CRICM), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), UCL - SSS/IONS/NEUR - Clinical Neuroscience, UCL - (MGD) Service de neurologie, Morrow David, A., Braunwald, Eugene, Bonaca Marc, P., Ameriso Sebastian, F., Dalby Anthony, J., Fish Mary, Polly, Fox Keith, A. A., Lipka Leslie, J., Liu, Xuan, Nicolau Jose, Carlo, Ophuis A. J., Oude, Paolasso, Ernesto, Scirica Benjamin, M., Spinar, Jindrich, Theroux, Pierre, Wiviott Stephen, D., Strony, John, Murphy Sabina, A., Golino, Paolo, and Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)
Subjects: Male, Pyridines, [SDV]Life Sciences [q-bio], Myocardial Infarction, Medizin, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Brain Ischemia, Lactones, 0302 clinical medicine, MESH: Peripheral Arterial Disease, Secondary Prevention, MESH: Double-Blind Method, 030212 general & internal medicine, Myocardial infarction, Stroke, Vorapaxar, MESH: Aged, Aspirin, MESH: Middle Aged, MESH: Risk, Cardiovascular diseases [NCEBP 14], MESH: Secondary Prevention, Hazard ratio, MESH: Brain Ischemia, General Medicine, Middle Aged, Clopidogrel, 3. Good health, MESH: Receptor, PAR-1, MESH: Myocardial Infarction, vorapaxar, secondary prevention, atherothrombotic events, Cardiovascular Diseases, MESH: Platelet Aggregation Inhibitors, Anesthesia, Retreatment, Platelet aggregation inhibitor, Female, Intracranial Hemorrhages, MESH: Hemorrhage, MESH: Intracranial Hemorrhages, MESH: Lactones, circulatory and respiratory physiology, medicine.drug, Risk, ISQUEMIA CEREBRAL, Hemorrhage, Placebo, MESH: Stroke, Peripheral Arterial Disease, 03 medical and health sciences, Double-Blind Method, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, medicine, Humans, Receptor, PAR-1, MESH: Retreatment, MESH: Kaplan-Meier Estimate, Aged, MESH: Humans, business.industry, MESH: Pyridines, MESH: Cardiovascular Diseases, medicine.disease, Settore MED/11 - Malattie Dell'Apparato Cardiovascolare, MESH: Male, business, MESH: Female, Platelet Aggregation Inhibitors
Abstract: BACKGROUND: Thrombin potently activates platelets through the protease-activated receptor PAR-1. Vorapaxar is a novel antiplatelet agent that selectively inhibits the cellular actions of thrombin through antagonism of PAR-1. METHODS: We randomly assigned 26,449 patients who had a history of myocardial infarction, ischemic stroke, or peripheral arterial disease to receive vorapaxar (2.5 mg daily) or matching placebo and followed them for a median of 30 months. The primary efficacy end point was the composite of death from cardiovascular causes, myocardial infarction, or stroke. After 2 years, the data and safety monitoring board recommended discontinuation of the study treatment in patients with a history of stroke owing to the risk of intracranial hemorrhage. RESULTS:At 3 years, the primary end point had occurred in 1028 patients (9.3%) in the vorapaxar group and in 1176 patients (10.5%) in the placebo group (hazard ratio for the vorapaxar group, 0.87; 95% confidence interval [CI], 0.80 to 0.94; P
Published: 2012

18. Clinical events as a function of proton pump inhibitor use, clopidogrel use, and cytochrome P450 2C19 genotype in a large nationwide cohort of acute myocardial infarction: results from the French Registry of Acute ST-Elevation and Non-ST-Elevation Myocardial Infarction (FAST-MI) registry

Author: Martine Gilard, Elodie Drouet, Thierry Lefèvre, Michel Hanssen, Geneviève Mulak, Hervé Lardoux, Laurent Bonello, Céline Verstuyft, Nicolas Danchin, Vincent Bataille, Jean Ferrières, Didier Blanchard, Philippe Gabriel Steg, Tabassome Simon, Pierre Coste, Service de cardiologie, Université Paris Diderot - Paris 7 (UPD7)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Hémostase, bio-ingénierie et remodelage cardiovasculaires (LBPC), Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Galilée, Optimisation des régulations physiologiques (ORPHY (EA 4324)), Université de Brest (UBO)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), CHU Saint-Antoine [APHP], Service de cardiologie [Toulouse], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Service de génétique moléculaire, pharmacogénétique et hormonologie, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Service de cardiologie [CHU Rouen], Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU), Université Paris Diderot - Paris 7 (UPD7)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre
Subjects: Male, MESH: Registries, Myocardial Infarction, MESH: Aryl Hydrocarbon Hydroxylases, 030204 cardiovascular system & hematology, MESH: Genotype, Cohort Studies, 0302 clinical medicine, MESH: Aged, 80 and over, 030212 general & internal medicine, Myocardial infarction, Registries, Stroke, MESH: Cohort Studies, MESH: Treatment Outcome, MESH: Aged, Aged, 80 and over, MESH: Middle Aged, ST elevation, Hazard ratio, Middle Aged, Clopidogrel, 3. Good health, MESH: Myocardial Infarction, Treatment Outcome, MESH: Platelet Aggregation Inhibitors, Cardiology, Platelet aggregation inhibitor, MESH: Purinergic P2Y Receptor Antagonists, Drug Therapy, Combination, Female, Aryl Hydrocarbon Hydroxylases, France, Cardiology and Cardiovascular Medicine, medicine.drug, MESH: Proton Pump Inhibitors, medicine.medical_specialty, Ticlopidine, MESH: Ticlopidine, Genotype, CYP2C19, 03 medical and health sciences, Physiology (medical), Internal medicine, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, Aged, MESH: Humans, business.industry, Proton Pump Inhibitors, medicine.disease, MESH: Male, Surgery, MESH: France, Cytochrome P-450 CYP2C19, MESH: Drug Therapy, Combination, Purinergic P2Y Receptor Antagonists, Myocardial infarction complications, business, MESH: Female, Platelet Aggregation Inhibitors
Abstract: Background— Clopidogrel requires metabolic activation by cytochrome P450 2C19 (CYP2C19). Proton pump inhibitors (PPIs) that inhibit CYP2C19 are commonly coadministered with clopidogrel to reduce the risk of gastrointestinal bleeding. This analysis compares treatment outcomes for patients in the French Registry of Acute ST-Elevation and Non–ST-Elevation Myocardial Infarction (FAST-MI) who did or did not receive clopidogrel and/or PPIs. Methods and Results— The FAST-MI registry included 3670 patients (2744 clopidogrel- and PPI-naïve patients) presenting with definite MI. Patients were categorized according to use of clopidogrel and/or PPI within 48 hours after hospital admission. PPI use was not associated with an increased risk for any of the main in-hospital events (in-hospital survival, reinfarction, stroke, bleeding, and transfusion). Likewise, PPI treatment was not an independent predictor of 1-year survival (hazard ratio, 0.97; 95% confidence interval [CI], 0.87 to 1.08; P =0.57) or 1-year MI, stroke, or death (hazard ratio, 0.98; 95% CI, 0.90 to 1.08; P =0.72). No differences were seen when the type of PPI or CYP2C19 genotype was taken into account. In the propensity-matched cohorts, the odds ratios for major in-hospital events in PPI versus no PPI were 0.29 (95% CI, 0.06 to 1.44) and 1.70 (95% CI, 0.10 to 30.3) for patients with 1 and 2 variant alleles, respectively. Similarly, the hazard ratio for 1-year events in hospital survivors was 0.68 (95% CI, 0.26 to 1.79) and 0.55 (95% CI, 0.06 to 5.30), respectively. Conclusion— PPI use was not associated with an increased risk of cardiovascular events or mortality in patients administered clopidogrel for recent MI, whatever the CYP2C19 genotype, although harm could not be formally excluded in patients with 2 loss-of-function alleles. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00673036.
Published: 2011

19. Poxytrins, a class of oxygenated products from polyunsaturated fatty acids, potently inhibit blood platelet aggregation

Author: Evelyne Véricel, Michel Lagarde, Michel Guichardant, Ping Chen, Régulations métaboliques, nutrition et diabètes (RMND), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), INSERM, Ministry of Education and Research, Lipides pour l'Industrie et la Sante (LISA) Carnot Institute, and Chinese Educational Council
Subjects: Thromboxane, Receptors, Thromboxane, Protectin D1, Biochemistry, chemistry.chemical_compound, Lipoxygenase, 15-lipoxygenase, MESH: Collagen, Neuroprotectin, Cyclic AMP, Dicarboxylic Acids, thromboxane receptor, MESH: Blood Platelets, MESH: Cyclic AMP, MESH: Platelet Aggregation, chemistry.chemical_classification, Arachidonic Acid, biology, Chemistry, Thromboxanes, MESH: Fatty Acids, Unsaturated, docosahexaenoic acid, docosatrienes, MESH: Receptors, Thromboxane, MESH: Docosahexaenoic Acids, Docosahexaenoic acid, platelet aggregation, MESH: Platelet Aggregation Inhibitors, Fatty Acids, Unsaturated, Platelet aggregation inhibitor, Arachidonic acid, Collagen, MESH: Oxygen, Biotechnology, Polyunsaturated fatty acid, Blood Platelets, Docosahexaenoic Acids, MESH: Prostaglandin-Endoperoxide Synthases, MESH: Thromboxanes, MESH: Cyclooxygenase Inhibitors, Isomerism, MESH: Dicarboxylic Acids, Genetics, Humans, MESH: Isomerism, Cyclooxygenase Inhibitors, Molecular Biology, MESH: Humans, MESH: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid, MESH: Arachidonic Acid, Oxygen, Prostaglandin-Endoperoxide Synthases, 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid, biology.protein, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Platelet Aggregation Inhibitors
Abstract: International audience; Docosahexaenoic acid (DHA), an important component of marine lipids, exhibits anti-inflammatory activity related to some of its oxygenated metabolites, such as neuroprotectin/protectin D1 [NPD1/PD1; 10(R),17(S)-dihydroxy-docosa-4Z,7Z, 11E,13E,15Z,19Z-hexaenoic acid] produced through the 15-lipoxygenase pathway. However, other metabolites from DHA can be produced through this pathway, and other polyunsaturated fatty acids (PUFAs) of nutritional value may be oxygenated as well. Their biological activities remain unknown. Isomers of protectin D1 were synthesized using soybean lipoxygenase and tested for their ability to inhibit human blood platelet aggregation. A geometric isomer called PDX, previously described with the 11E,13Z,15E geometry, instead of 11E,13E,15Z in PD1, inhibited platelet aggregation at submicromolar concentrations when induced by either collagen, arachidonic acid, or thromboxane. The inhibition occurred at the level of both the cyclooxygenase activity and thromboxane receptor site. Interestingly, all the metabolites tested exhibiting the E,Z,E-conjugated triene were active, whereas E,E,Z trienes (as in PD1) or all-trans (E,E,E) trienes were inactive. We conclude that PDX and other oxygenated products from PUFAs of nutritional interest, having the E,Z,E-conjugated triene motif and collectively named poxytrins (PUFA oxygenated trienes), might have antithrombotic potential.
Published: 2011

20. Poxytrins, a class of oxygenated products from polyunsaturated fatty acids, potently inhibit blood platelet aggregation

Author: Chen, Ping, Véricel, Evelyne, Lagarde, Michel, Guichardant, Michel, Régulations métaboliques, nutrition et diabètes (RMND), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), INSERM, Ministry of Education and Research, Lipides pour l'Industrie et la Sante (LISA) Carnot Institute, Chinese Educational Council, and Vericel, Evelyne
Subjects: MESH: Humans, MESH: Prostaglandin-Endoperoxide Synthases, MESH: Thromboxanes, MESH: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid, MESH: Fatty Acids, Unsaturated, docosahexaenoic acid, docosatrienes, MESH: Arachidonic Acid, MESH: Receptors, Thromboxane, MESH: Cyclooxygenase Inhibitors, MESH: Docosahexaenoic Acids, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, MESH: Dicarboxylic Acids, 15-lipoxygenase, platelet aggregation, MESH: Platelet Aggregation Inhibitors, MESH: Collagen, MESH: Isomerism, thromboxane receptor, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, MESH: Oxygen, MESH: Blood Platelets, MESH: Cyclic AMP, MESH: Platelet Aggregation
Abstract: International audience; Docosahexaenoic acid (DHA), an important component of marine lipids, exhibits anti-inflammatory activity related to some of its oxygenated metabolites, such as neuroprotectin/protectin D1 [NPD1/PD1; 10(R),17(S)-dihydroxy-docosa-4Z,7Z, 11E,13E,15Z,19Z-hexaenoic acid] produced through the 15-lipoxygenase pathway. However, other metabolites from DHA can be produced through this pathway, and other polyunsaturated fatty acids (PUFAs) of nutritional value may be oxygenated as well. Their biological activities remain unknown. Isomers of protectin D1 were synthesized using soybean lipoxygenase and tested for their ability to inhibit human blood platelet aggregation. A geometric isomer called PDX, previously described with the 11E,13Z,15E geometry, instead of 11E,13E,15Z in PD1, inhibited platelet aggregation at submicromolar concentrations when induced by either collagen, arachidonic acid, or thromboxane. The inhibition occurred at the level of both the cyclooxygenase activity and thromboxane receptor site. Interestingly, all the metabolites tested exhibiting the E,Z,E-conjugated triene were active, whereas E,E,Z trienes (as in PD1) or all-trans (E,E,E) trienes were inactive. We conclude that PDX and other oxygenated products from PUFAs of nutritional interest, having the E,Z,E-conjugated triene motif and collectively named poxytrins (PUFA oxygenated trienes), might have antithrombotic potential.
Published: 2011

21. Efficacy and safety of glycoprotein IIb/IIIa receptor antagonists for patients undergoing percutaneous coronary intervention within twelve hours of fibrinolysis

Author: Belle, Loic, Fourny, Magali, Reynaud, Thomas, Hammer, Laure, Vanzetto, Gérald, Labarère, José, Renseigné, Non, Unité de qualitique et d'évaluation médicale - pole Santé Publique, CHU Grenoble, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Clinique de réanimation médicale, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon, Radiopharmaceutiques biocliniques, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), BCM, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, and Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-CHU Grenoble
Subjects: Male, Time Factors, MESH: Chi-Square Distribution, MESH: Registries, medicine.medical_treatment, Myocardial Infarction, MESH: Logistic Models, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Coronary Angiography, MESH: Risk Assessment, Gastroenterology, 0302 clinical medicine, Recurrence, Risk Factors, MESH: Risk Factors, Odds Ratio, Thrombolytic Therapy, Hospital Mortality, Registries, 030212 general & internal medicine, Myocardial infarction, Angioplasty, Balloon, Coronary, Stroke, MESH: Treatment Outcome, MESH: Aged, MESH: Thrombolytic Therapy, MESH: Middle Aged, General Medicine, Middle Aged, Receptor antagonist, MESH: Platelet Glycoprotein GPIIb-IIIa Complex, 3. Good health, MESH: Angioplasty, Balloon, Coronary, MESH: Myocardial Infarction, Treatment Outcome, MESH: Platelet Aggregation Inhibitors, Cardiology, Female, France, Cardiology and Cardiovascular Medicine, MESH: Hemorrhage, medicine.medical_specialty, medicine.drug_class, Hemorrhage, Platelet Glycoprotein GPIIb-IIIa Complex, MESH: Drug Administration Schedule, Risk Assessment, Drug Administration Schedule, MESH: Stroke, 03 medical and health sciences, Angioplasty, Internal medicine, Fibrinolysis, medicine, Humans, MESH: Patient Selection, Radiology, Nuclear Medicine and imaging, MESH: Hospital Mortality, Propensity Score, MESH: Kaplan-Meier Estimate, Aged, Chi-Square Distribution, MESH: Humans, business.industry, Patient Selection, MESH: Time Factors, Percutaneous coronary intervention, Odds ratio, MESH: Propensity Score, medicine.disease, MESH: Male, MESH: Odds Ratio, MESH: Coronary Angiography, MESH: Recurrence, MESH: France, Logistic Models, Conventional PCI, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, MESH: Female, Platelet Aggregation Inhibitors
Abstract: International audience; OBJECTIVE: To compare clinical outcomes between glycoprotein IIb/IIIa receptor antagonist recipients and nonrecipients who underwent percutaneous coronary intervention (PCI) within 12 hr of fibrinolysis. BACKGROUND: Despite limited evidence, glycoprotein IIb/IIIa receptor antagonists are widely used in ST-elevation myocardial infarction (STEMI) patients undergoing routine early or rescue PCI after fibrinolysis. METHODS: We evaluated 87 and 556 glycoprotein IIb/IIIa receptor antagonist recipients and nonrecipients enrolled in a regional registry of STEMI between October 2002 and December 2005. The primary efficacy endpoint was a composite of death from any cause, reinfarction, and stroke at 1 year of follow-up. The primary safety endpoint was the rate of in-hospital major bleeding that was not related to coronary artery bypass grafting. RESULTS: The primary efficacy endpoint occurred in 12% (10 of 81) and 13% (72 of 525) of glycoprotein IIb/IIIa receptor antagonist recipients and nonrecipients, respectively (P = 0.74). The corresponding rates of major bleeding during index hospitalization were 4.8% (4 of 84) and 5.1% (28 of 544) (P = 0.88), respectively. Two glycoprotein IIb/IIIa receptor antagonist recipients and five nonrecipients experienced intracranial hemorrhage. After adjusting for propensity score, the odds of primary efficacy (odds ratio, 0.79; 95% confidence interval, 0.34-1.83) and safety (odds ratio, 0.75; 95% confidence interval, 0.22-2.62) endpoints did not differ according to the use of glycoprotein IIb/IIIa receptor antagonists. CONCLUSION: In this observational cohort study of unselected patients with STEMI, the administration of glycoprotein IIb/IIIa receptor antagonists provided no additional benefit to PCI performed within 12 hr of fibrinolysis, nor did it compromise patient safety.
Published: 2011

22. Antithrombotic medications and recurrent miscarriage

Author: Kitty W. M. Bloemenkamp, Jantien Visser, Danielle Cohen, Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Département de Médecine Interne et Pneumologie [Brest] (DMIP - Brest), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre d'Investigation Clinique (CIC - Brest), and Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Abortion, Habitual, medicine.medical_specialty, MEDLINE, Abortion, MESH: Anticoagulants, 03 medical and health sciences, 0302 clinical medicine, MESH: Pregnancy, Bias, Double-Blind Method, Pregnancy, Recurrent miscarriage, Antithrombotic, Humans, Medicine, MESH: Double-Blind Method, 030212 general & internal medicine, MESH: Heparin, Low-Molecular-Weight, MESH: Aspirin, ComputingMilieux_MISCELLANEOUS, 030219 obstetrics & reproductive medicine, MESH: Humans, Aspirin, MESH: Abortion, Habitual, business.industry, Obstetrics, Anticoagulants, General Medicine, Heparin, Heparin, Low-Molecular-Weight, MESH: Bias (Epidemiology), medicine.disease, MESH: Platelet Aggregation Inhibitors, Female, business, MESH: Female, Platelet Aggregation Inhibitors, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract: International audience
Published: 2010

23. Letter by Aboyans et al Regarding Article, 'Smoking, Clopidogrel, and Mortality in Patients With Established Cardiovascular Disease'

Author: Philippe Lacroix, Alexandre Le Guyader, Victor Aboyans, Service de Chirurgie Thoracique et Vasculaire - Médecine vasculaire [CHU Limoges], CHU Limoges, Neuroépidémiologie Tropicale et Comparée (NETEC), and Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Université de Limoges (UNILIM)
Subjects: MESH: Smoking, medicine.medical_specialty, MESH: Ticlopidine, Alternative medicine, Disease, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, MESH: Risk Factors, Physiology (medical), medicine, In patient, cardiovascular diseases, 030212 general & internal medicine, Intensive care medicine, ComputingMilieux_MISCELLANEOUS, MESH: Humans, business.industry, MESH: Cardiovascular Diseases, Clopidogrel, 3. Good health, Surgery, MESH: Platelet Aggregation Inhibitors, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Cardiology and Cardiovascular Medicine, business, MESH: Hemorrhage, circulatory and respiratory physiology, medicine.drug
Abstract: To the Editor: Berger and colleagues1 are commended for their interesting and hypothesis-generating posthoc analysis of the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) trial published recently in Circulation . To better understand the potential pathways leading to an enhanced protective effect of clopidogrel in smokers, several issues need further discussion and analysis. First, the protective effect of clopidogrel in smokers in this report contrasts with the …
Published: 2010

24. Leberagin-C, A disintegrin-like/cysteine-rich protein from Macrovipera lebetina transmediterranea venom, inhibits alphavbeta3 integrin-mediated cell adhesion

Author: Ines Limam, Olfa Kallech-Ziri, Salma Taboubi, Asma Hammami, José Luis, Jed Jebali, Amine Bazaa, Hafedh Mejdoub, Mohamed El Ayeb, Raoudha Zouari-Kessentini, Najet Srairi-Abid, Naziha Marrakchi, Laboratoire des Venins et Toxines, Institut Pasteur de Tunis, Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), USCR séquenceur de protéines, Faculté des Sciences de Sfax, Université de Sfax - University of Sfax-Université de Sfax - University of Sfax, Faculté de Médecine, Faculte de Medecine de Tunis, and Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Aix Marseille Université (AMU)
Subjects: Models, Molecular, Integrins, Platelet Aggregation, Disintegrins, MESH: Viperidae, MESH: Antigens, Neoplasm, MESH: Amino Acid Sequence, MESH: Base Sequence, Conserved sequence, MESH: Protein Structure, Tertiary, Protein structure, Viperidae, MESH: Animals, Peptide sequence, MESH: Platelet Aggregation, 0303 health sciences, biology, 030302 biochemistry & molecular biology, MESH: Integrins, MESH: Integrin alphaVbeta3, Biochemistry, MESH: Platelet Aggregation Inhibitors, Jararhagin, Integrin alpha2beta1, MESH: Viper Venoms, Macrovipera lebetina, MESH: Models, Molecular, Integrin alpha5beta1, MESH: Cell Line, Tumor, Molecular Sequence Data, Integrin, MESH: Sequence Alignment, Viper Venoms, MESH: Cell Adhesion, 03 medical and health sciences, Antigens, Neoplasm, Cell Line, Tumor, Cell Adhesion, Disintegrin, Animals, Humans, Amino Acid Sequence, Cysteine, MESH: Disintegrins, Cell adhesion, Molecular Biology, 030304 developmental biology, MESH: Molecular Sequence Data, MESH: Humans, Base Sequence, MESH: Integrin alpha5beta1, MESH: Cysteine, Integrin alphaVbeta3, biology.organism_classification, Molecular biology, Protein Structure, Tertiary, biology.protein, Sequence Alignment, Platelet Aggregation Inhibitors, MESH: Integrin alpha2beta1
Abstract: International audience; Leberagin-C, a new member of the disintegrin-like/cysteine-rich (D/C) family, was purified to homogeneity from the venom of Tunisian snake Macrovipera lebetina transmediterranea. It is a monomeric protein with a molecular mass of 25,787 Da. Its complete sequence of 205 amino acid residues was established by cDNA cloning. The leberagin-C shows many conserved sequences with other known D/C proteins, like the SECD binding sites and a pattern of 28 cysteines. It is the first purified protein from M. lebetina transmediterranea with only two disintegrin-like/cysteine-rich domains. Leberagin-C is able to inhibit platelet aggregation induced by thrombin and arachidonic acid with IC(50) of 40 and 50 nM respectively. It was also able to inhibit the adhesion of melanoma tumour cells on fibrinogen and fibronectin, by interfering with the function of alphavbeta3 and, to a lesser extent, with alphavbeta6 and alpha5beta1 integrins. To our knowledge, leberagin-C is the sole described D/C protein that does not specifically interact with the alpha2beta1 integrin. Structure-activity relationship study of leberagin-C suggested that there are some important amino acid differences with jararhagin, the most studied PIII metalloprotease from Bothrops jararaca, notably around the SECD motif in its disintegrin-like domain. Other regions implicated in leberagin-C specificities could not be excluded.
Published: 2010

25. Improving the management of non-ST elevation acute coronary syndromes: systematic evaluation of a quality improvement programme European QUality Improvement Programme for Acute Coronary Syndrome: the EQUIP-ACS project protocol and design

Author: Jacques Machecourt, Bertil Lindahl, Filippo Ottani, Marcus Flather, Daphne Babalis, Jean Booth, Alfredo Bardají, Héctor Bueno, Anthony R. Brady, Grzegorz Opolski, Philippe Gabriel Steg, Mats Bojestig, BMC, Ed., Clinical Trials and Evaluation Unit, Royal Brompton Hospital, Hospital General Universitario 'Gregorio Marañón' [Madrid], Hémostase, bio-ingénierie et remodelage cardiovasculaires (LBPC), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut Galilée-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Warszawski Uniwersytet Medyczny, Ospedale Morgagni Pierantoni, Clinique Cardiologie et Hypertension Artérielle, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon, Hospital Universitari de Tarragona Joan XXIII, Universitat Rovira i Virgili-IISPV, Department of Heath care, Jönköping County Council, Sealed Envelope Ltd., Uppsala Clinical Research, Uppsala University Hospital, and Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Galilée
Subjects: Quality management, Time Factors, Cost-Benefit Analysis, SEGMENT-ELEVATION, Medicine (miscellaneous), Angiotensin-Converting Enzyme Inhibitors, 030204 cardiovascular system & hematology, Research & Experimental Medicine, GUIDELINES, Coronary Angiography, MESH: Risk Assessment, 0302 clinical medicine, Risk Factors, MESH: Risk Factors, Health care, Pharmacology (medical), 030212 general & internal medicine, Program Development, CARDIOLOGY, MESH: Treatment Outcome, OUTCOMES, MESH: Program Evaluation, MESH: Research Design, Health services research, MESH: Angiotensin-Converting Enzyme Inhibitors, MESH: Adrenergic beta-Antagonists, Health Care Costs, 3. Good health, Europe, INSIGHTS, Outcome and Process Assessment, Health Care, Treatment Outcome, Medicine, Research & Experimental, Research Design, MESH: Platelet Aggregation Inhibitors, Platelet aggregation inhibitor, Health Services Research, Life Sciences & Biomedicine, MESH: Outcome and Process Assessment (Health Care), MESH: Health Services Research, medicine.medical_specialty, Acute coronary syndrome, ACUTE MYOCARDIAL-INFARCTION, Evidence-based practice, Adrenergic beta-Antagonists, MESH: Health Care Costs, MESH: Anticoagulants, 1102 Cardiovascular Medicine And Haematology, Risk Assessment, 03 medical and health sciences, General & Internal Medicine, Study protocol, MESH: Program Development, medicine, MESH: Quality Indicators, Health Care, Humans, Acute Coronary Syndrome, MESH: Hydroxymethylglutaryl-CoA Reductase Inhibitors, Quality Indicators, Health Care, UNSTABLE ANGINA, Science & Technology, MESH: Humans, business.industry, Unstable angina, MESH: Time Factors, Anticoagulants, 1103 Clinical Sciences, CARE, medicine.disease, Outcome and Process Assessment (Health Care), MESH: Acute Coronary Syndrome, MESH: Coronary Angiography, Clinical trial, Cardiovascular System & Hematology, HOSPITALS, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, REGISTRY, Emergency medicine, Physical therapy, Feasibility Studies, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Europe, Hydroxymethylglutaryl-CoA Reductase Inhibitors, business, MESH: Feasibility Studies, Platelet Aggregation Inhibitors, Program Evaluation, MESH: Cost-Benefit Analysis
Abstract: International audience; BACKGROUND: Acute coronary syndromes, including myocardial infarction and unstable angina, are important causes of premature mortality, morbidity and hospital admissions. Acute coronary syndromes consume large amounts of health care resources, and have a major negative economic and social impact through days lost at work, support for disability, and coping with the psychological consequences of illness. Several registries have shown that evidence based treatments are under-utilised in this patient population, particularly in high-risk patients. There is evidence that systematic educational programmes can lead to improvement in the management of these patients. Since application of the results of important clinical trials and expert clinical guidelines into clinical practice leads to improved patient care and outcomes, we propose to test a quality improvement programme in a general group of hospitals in Europe. METHODS/DESIGN: This will be a multi-centre cluster-randomised study in 5 European countries: France, Spain, Poland, Italy and the UK. Thirty eight hospitals will be randomised to receive a quality improvement programme or no quality improvement programme. Centres will enter data for all eligible non-ST segment elevation acute coronary syndrome patients admitted to their hospital for a period of approximately 10 months onto the study database and the sample size is estimated at 2,000-4,000 patients. The primary outcome is a composite of eight measures to assess aggregate potential for improvement in the management and treatment of this patient population (risk stratification, early coronary angiography, anticoagulation, beta-blockers, statins, ACE-inhibitors, clopidogrel as a loading dose and at discharge). After the quality improvement programme, each of the eight measures will be compared between the two groups, correcting for cluster effect. DISCUSSION: If we can demonstrate important improvements in the quality of patient care as a result of a quality improvement programme, this could lead to a greater acceptance that such programmes should be incorporated into routine health training for health professionals and hospital managers. TRIAL REGISTRATION: Clinicaltrials.gov NCT00716430.
Published: 2010

26. Platelet hyperactivity during exercise leading to iterative coronary stent thrombosis: clinical implications

Author: Jacques Machecourt, Gérald Vanzetto, Benoit Polack, Mohamed Sahnoun, Olivier Ormezzano, Clinique Cardiologie et Hypertension Artérielle, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon, TheREx, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Radiopharmaceutiques biocliniques, and Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: MESH: Coronary Thrombosis, Male, medicine.medical_specialty, Acute coronary syndrome, Stent thrombosis, medicine.medical_treatment, 030204 cardiovascular system & hematology, Coronary Restenosis, 03 medical and health sciences, Antiplatelet treatments Clopidogrel, 0302 clinical medicine, MESH: Coronary Restenosis, Recurrence, Internal medicine, Coronary stent, Medicine, MESH: Platelet Activation, Humans, Platelet, 030212 general & internal medicine, Platelet activation, cardiovascular diseases, Exercise, Hematology, MESH: Humans, MESH: Middle Aged, business.industry, Coronary Thrombosis, Middle Aged, medicine.disease, Clopidogrel, Platelet Activation, Thrombosis, MESH: Male, 3. Good health, MESH: Recurrence, MESH: Stents, MESH: Exercise, MESH: Platelet Aggregation Inhibitors, Cardiology, Stents, Cardiology and Cardiovascular Medicine, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Platelet Aggregation Inhibitors, medicine.drug
Abstract: International audience; Exercise may induce platelet activation in spite of using antiplatelet treatment. We present a case where the initial acute coronary syndrome and the iterative stent thrombosis always occurred after intense and prolonged physical effort. For this patient the at rest response to platelet inhibition with antiplatelet treatments was assessed as adequate, but after exercise the patient developed platelet activation which could be the trigger of his stent thrombosis.
Published: 2009

27. Cardiovascular rehabilitation increase arterial compliance in type 2 diabetic patients with coronary artery disease

Author: Laurent Mourot, S. Maunier, Philippe Blanc, Alain Boussuges, Xavier Debussche, P. Campo, Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( EA 3920) (PCVP / CARDIO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Institut de Médecine Navale du Service de Santé des Armées (IMNSSA), Service de Santé des Armées, Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( PCVP / CARDIO ), Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ) -Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), Centre d'Investigation Clinique de Besançon ( CICB ), Etablissement Français du Sang Bourgogne Franche-Comté-Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Franche-Comté ( UFC ), Institut de Médecine Navale du Service de Santé des Armées ( IMNSSA ), Institut de biologie et chimie des protéines [Lyon] ( IBCP ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), and Jallat, Isabelle
Subjects: MESH : Manometry, Vasodilator Agents, Endocrinology, Diabetes and Metabolism, MESH: Diabetic Angiopathies, MESH : Arterioles, Hemodynamics, Coronary Disease, Type 2 diabetes, 030204 cardiovascular system & hematology, MESH : Antihypertensive Agents, Body Mass Index, Coronary artery disease, 0302 clinical medicine, Endocrinology, MESH : Diabetes Mellitus, Type 2, MESH : Exercise, Heart Rate, 030212 general & internal medicine, MESH: Heart Rate, Diuretics, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, MESH : Hemodynamics, MESH : Diuretics, MESH: Manometry, General Medicine, Stroke volume, MESH : Platelet Aggregation Inhibitors, MESH: Patient Compliance, 3. Good health, MESH: Pulse, Arterioles, MESH: Platelet Aggregation Inhibitors, Cardiology, MESH: Diabetes Mellitus, Type 2, medicine.medical_specialty, MESH: Hemodynamics, Manometry, MESH: Patient Education as Topic, MESH : Vasodilator Agents, MESH : Patient Compliance, MESH: Body Mass Index, 03 medical and health sciences, MESH: Arterioles, Patient Education as Topic, Internal medicine, Diabetes mellitus, MESH : Pulse, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, Internal Medicine, medicine, Humans, MESH: Diuretics, Pulse, MESH: Hydroxymethylglutaryl-CoA Reductase Inhibitors, Exercise, Antihypertensive Agents, MESH: Antihypertensive Agents, MESH: Humans, business.industry, MESH : Diabetic Angiopathies, MESH : Heart Rate, MESH : Humans, MESH : Hydroxymethylglutaryl-CoA Reductase Inhibitors, Type 2 Diabetes Mellitus, medicine.disease, MESH: Vasodilator Agents, Compliance (physiology), MESH : Body Mass Index, Diabetes Mellitus, Type 2, MESH: Exercise, Arterial stiffness, MESH : Coronary Disease, Patient Compliance, MESH: Coronary Disease, Hydroxymethylglutaryl-CoA Reductase Inhibitors, MESH : Patient Education as Topic, business, Diabetic Angiopathies, Platelet Aggregation Inhibitors, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; AIMS: The effect of a cardiovascular rehabilitation program on arterial compliance in type 2 diabetes mellitus with coronary disease was studied. METHODS: Hemodynamic data and arterial compliance were measured with a tonometer (HDI/Pulse wave CR-2000) in coronary artery disease patients with (n=32) and without (n=24) type 2 diabetes before and after a 6-week multidisciplinary cardiac rehabilitation program. RESULTS: A decrease in heart rate and an increase in stroke volume without significant change in resting cardiac output were obtained in diabetic patients. Arterial compliance of both small and large arteries was significantly increased. In 10 diabetic patients, this increase could be related to an increase in the anti-hypertensive treatment and to the decreased blood pressure. In the 22 remainders, the small artery compliance was significantly increased independently of blood pressure change. CONCLUSIONS: Exercise training as well as optimization of diabetes and dyslipidemia treatment could explain the improvement of arterial compliance. If these changes are long-lasting and if they improve prognosis remains to be evaluated.
Published: 2009

28. Antagonists of the EP3 receptor for prostaglandin E2 are novel antiplatelet agents that do not prolong bleeding

Author: Jean-Etienne Fabre, Wayne Zeller, Margret Thorsteinsdottir, Mark E. Gurney, David E. Zembower, Peng Yu, Alex Polozov, Jasbir Singh, Emmanuel Onua, Jon Mar Bjornsson, Nian Zhou, Kari Stefansson, Maria Bjarnadottir, Gudmundur Sigthorsson, Georgeta Hategen, Thorkell Andresson, Jun Zhang, Alex S. Kiselyov, Rama K. Mishra, Jose Ramirez, Olafur T. Magnusson, deCODE Chemistry, deCODE Genetics, deCODE genetics [Reykjavik], Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Louis Pasteur - Strasbourg I, Peney, Maité, and Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Platelet Aggregation, medicine.medical_treatment, 030204 cardiovascular system & hematology, Pharmacology, Biochemistry, MESH: Receptors, Purinergic P2Y12, MESH: Receptors, Prostaglandin E, 0302 clinical medicine, MESH: Prostaglandin Antagonists, Purinergic P2 Receptor Antagonists, MESH: Animals, Platelet, Sulfones, Prostaglandin E2, Receptor, MESH: Receptors, Prostaglandin E, EP3 Subtype, MESH: Platelet Aggregation, 0303 health sciences, medicine.diagnostic_test, Chemistry, MESH: Dinoprostone, MESH: Sulfones, General Medicine, Clopidogrel, Receptors, Purinergic P2Y12, MESH: Platelet Aggregation Inhibitors, Receptors, Prostaglandin E, EP3 Subtype, Molecular Medicine, Female, MESH: Hemorrhage, Prostaglandin E, medicine.drug, Agonist, Ticlopidine, MESH: Rats, MESH: Ticlopidine, Prostaglandin Antagonists, medicine.drug_class, Hemorrhage, Dinoprostone, 03 medical and health sciences, Bleeding time, medicine, Animals, Humans, Receptors, Prostaglandin E, MESH: Thrombosis, Platelet activation, 030304 developmental biology, Acrylamides, MESH: Humans, MESH: Acrylamides, Thrombosis, MESH: Male, Rats, MESH: Purinergic P2 Receptor Antagonists, Immunology, MESH: Female, Platelet Aggregation Inhibitors
Abstract: International audience; Myocardial infarction and stroke are caused by blood clots forming over a ruptured or denuded atherosclerotic plaque (atherothrombosis). Production of prostaglandin E(2) (PGE(2)) by an inflamed plaque exacerbates atherothrombosis and may limit the effectiveness of current therapeutics. Platelets express multiple G-protein coupled receptors, including receptors for ADP and PGE(2). ADP can mobilize Ca(2+) and through the P(2)Y(12) receptor can inhibit cAMP production, causing platelet activation and aggregation. Clopidogrel (Plavix), a selective P(2)Y(12) antagonist, prevents platelets from clotting but thereby increases the risk of severe or fatal bleeding. The platelet EP(3) receptor for PGE(2), like the P(2)Y(12) receptor, also inhibits cAMP synthesis. However, unlike ADP, facilitation of platelet aggregation via the PGE(2)/EP(3) pathway is dependent on co-agonists that can mobilize Ca(2+). We used a ligand-based design strategy to develop peri-substituted bicylic acylsulfonamides as potent and selective EP(3) antagonists. We show that DG-041, a selective EP(3) antagonist, inhibits PGE(2) facilitation of platelet aggregation in vitro and ex vivo. PGE(2) can resensitize platelets to agonist even when the P(2)Y(12) receptor has been blocked by clopidogrel, and this can be inhibited by DG-041. Unlike clopidogrel, DG-041 does not affect bleeding time in rats, nor is bleeding time further increased when DG-041 is co-administered with clopidogrel. This indicates that EP(3) antagonists potentially have a superior safety profile compared to P(2)Y(12) antagonists and represent a novel class of antiplatelet agents.
Published: 2009

29. Antiplatelet therapy in patients with anticoagulants undergoing percutaneous coronary stenting (from STENTIng and oral antiCOagulants [STENTICO])

Author: Martine, Gilard, Didier, Blanchard, Gérard, Helft, Didier, Carrier, Helene, Eltchaninoff, Loic, Belle, Gérard, Finet, Hervé, Le Breton, Jacques, Boschat, J M, Clerc, Service de cardiologie [Brest], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de Cardiologie B, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de cardiologie [Toulouse], Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Service de cardiologie [CHU Rouen], Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU), Department of Hemodynamics and Interventional Cardiology, Institut National de la Santé et de la Recherche Médicale (INSERM), Service de cardiologie et maladies vasculaires [Rennes] = Cardiac, Thoracic, and Vascular Surgery [Rennes], CHU Pontchaillou [Rennes], STENTICO Investigators, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Service de cardiologie et maladies vasculaires, Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes]
Subjects: Male, Percutaneous, Time Factors, medicine.medical_treatment, Coronary Artery Disease, 030204 cardiovascular system & hematology, 0302 clinical medicine, MESH: Aged, 80 and over, [INFO.INFO-TS]Computer Science [cs]/Signal and Image Processing, 030212 general & internal medicine, MESH: Coronary Artery Disease, Angioplasty, Balloon, Coronary, Stroke, MESH: Treatment Outcome, MESH: Aged, Aged, 80 and over, Anticoagulant, Drug-Eluting Stents, 3. Good health, MESH: Angioplasty, Balloon, Coronary, Treatment Outcome, MESH: Platelet Aggregation Inhibitors, Anesthesia, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Drug Therapy, Combination, Female, Cardiology and Cardiovascular Medicine, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, MESH: Hemorrhage, MESH: Drug-Eluting Stents, medicine.medical_specialty, medicine.drug_class, Hemorrhage, MESH: Anticoagulants, 03 medical and health sciences, Pharmacotherapy, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Angioplasty, medicine, Humans, Aged, MESH: Humans, business.industry, MESH: Time Factors, Percutaneous coronary intervention, Anticoagulants, medicine.disease, MESH: Male, Surgery, Discontinuation, MESH: Drug Therapy, Combination, Conventional PCI, business, MESH: Female, Platelet Aggregation Inhibitors
Abstract: International audience; We evaluated the safety and efficacy of dual antiplatelet therapy, in association with oral anticoagulant (OAC) therapy, in patients undergoing percutaneous coronary intervention (PCI). The use of this triple therapy increases the rate of adverse outcomes, as shown by retrospective studies. In this first prospective multicenter registry STENTIng and oral antiCOagulation (STENTICO), all patients with OAC therapy undergoing PCI were included and followed up at 2 and 12 months. A total of 359 patients were included from 40 French centers. In 234 (65.2%; group 1) of these 359 patients, OAC therapy was discontinued (22 +/- 31 days). In 125 patients (34.8%; group 2), triple therapy was continued. The baseline characteristics were similar in the 2 groups. In group 2, a radial approach was more often used (65.6% vs 43.8%, p = 0.003), fewer drug-eluting stents were implanted (33.3% vs 24.8%, p = 0.06), and fewer anti-glycoprotein IIb/IIIa antagonists were prescribed (5.6% vs 8.5%, p = 0.02). The stroke rate did not differ significantly, at 3.0% (95% confidence interval 0.8% to 5.2%) for group 1 versus 0.8% (95% confidence interval -0.8% to 2.4%) in group 2. Severe and moderate bleeding, according to the Global Use of Strategies to Open Coronary Arteries (GUSTO) criteria, occurred in 2.1% and 6.4% of groups 1 and 2, respectively (p = 0.04). A significant difference in bleeding risk was found between the femoral and radial approaches (10.3% vs 3.8%, respectively; p = 0.01). In conclusion, adding dual antiplatelet therapy to pre-existing OAC therapy increases the post-PCI bleeding risk. Temporary discontinuation decreased this bleeding risk but tended to increase the risk of stroke. A radial approach for PCI could be a good alternative to the conventional femoral route to avoid bleeding.
Published: 2009

30. Effect of clopidogrel added to aspirin in patients with atrial fibrillation

Author: Mario Talajic, Keith Fox, Maria Christiane Valeria Braga Braile-Sternieri, Salim Yusuf, ANDRÉ SCHMIDT, Graeme Hankey, Laszlo Olah, Fabio Turazza, Philippe Gabriel STEG, Fernando Lanas, Dario C Sobral Filho, Gregory Albers, Sergey Golitsyn, Population Health Research Institute, University of Texas Health Center, The University of Texas Health Science Center at Houston (UTHealth), Goethe University Hospital, Brigham and Women's Hospital [Boston], ACTIVE Investigators, ACS - Amsterdam Cardiovascular Sciences, APH - Amsterdam Public Health, Cardiology, Graduate School, Connolly, Sj, Pogue, J, Hart, Rg, Hohnloser, Sh, Pfeffer, M, Chrolavicius, S, Yusuf, S, Active, Investigator, and Pizzolato, Gilberto
Subjects: Male, Vitamin K, Embolism, Myocardial Infarction, 030204 cardiovascular system & hematology, 0302 clinical medicine, [INFO.INFO-TS]Computer Science [cs]/Signal and Image Processing, Atrial Fibrillation, MESH: Double-Blind Method, MESH: Incidence, Myocardial infarction, Stroke, MESH: Aged, Aspirin, MESH: Middle Aged, MESH: Risk, Incidence, Atrial fibrillation, MESH: Follow-Up Studies, General Medicine, Middle Aged, Clopidogrel, 3. Good health, MESH: Myocardial Infarction, MESH: Atrial Fibrillation, MESH: Platelet Aggregation Inhibitors, MESH: Vascular Diseases, Cardiology, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Drug Therapy, Combination, Female, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, MESH: Hemorrhage, medicine.drug, Risk, medicine.medical_specialty, Ticlopidine, Stroke Atrial fibrillation anticoagulation, MESH: Ticlopidine, Hemorrhage, Placebo, MESH: Stroke, 03 medical and health sciences, Double-Blind Method, Internal medicine, medicine, Humans, Platelet activation, cardiovascular diseases, Vascular Diseases, MESH: Aspirin, Aged, MESH: Humans, business.industry, Warfarin, MESH: Vitamin K, medicine.disease, MESH: Male, MESH: Drug Therapy, Combination, business, MESH: Female, MESH: Embolism, 030217 neurology & neurosurgery, Platelet Aggregation Inhibitors, Follow-Up Studies
Abstract: Udgivelsesdato: 2009-May-14 BACKGROUND: Vitamin K antagonists reduce the risk of stroke in patients with atrial fibrillation but are considered unsuitable in many patients, who usually receive aspirin instead. We investigated the hypothesis that the addition of clopidogrel to aspirin would reduce the risk of vascular events in patients with atrial fibrillation. METHODS: A total of 7554 patients with atrial fibrillation who had an increased risk of stroke and for whom vitamin K-antagonist therapy was unsuitable were randomly assigned to receive clopidogrel (75 mg) or placebo, once daily, in addition to aspirin. The primary outcome was the composite of stroke, myocardial infarction, non-central nervous system systemic embolism, or death from vascular causes. RESULTS: At a median of 3.6 years of follow-up, major vascular events had occurred in 832 patients receiving clopidogrel (6.8% per year) and in 924 patients receiving placebo (7.6% per year) (relative risk with clopidogrel, 0.89; 95% confidence interval [CI], 0.81 to 0.98; P=0.01). The difference was primarily due to a reduction in the rate of stroke with clopidogrel. Stroke occurred in 296 patients receiving clopidogrel (2.4% per year) and 408 patients receiving placebo (3.3% per year) (relative risk, 0.72; 95% CI, 0.62 to 0.83; P
Published: 2009

31. [Drugs and venous thromboembolism]

Author: K, Lacut, D, Mottier, P, Pottier, Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Service de médecine interne [Nantes], and Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes)
Subjects: Psychotropic Drugs, MESH: Humans, Aspirin, MESH: Psychotropic Drugs, Estrogen Replacement Therapy, MESH: Thalidomide, Angiogenesis Inhibitors, Venous Thromboembolism, equipment and supplies, MESH: Estrogen Replacement Therapy, Thalidomide, MESH: Venous Thromboembolism, MESH: Platelet Aggregation Inhibitors, Humans, cardiovascular diseases, Hydroxymethylglutaryl-CoA Reductase Inhibitors, MESH: Aspirin, MESH: Hydroxymethylglutaryl-CoA Reductase Inhibitors, Platelet Aggregation Inhibitors, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, MESH: Angiogenesis Inhibitors
Abstract: International audience; Among the many factors likely to favour the occurrence of venous thromboembolism (VTE), exposure to certain drugs has to be taken into account. Although hormone treatments, oral contraception and hormone replacement therapy (HRT) for menopause have been studied, these are not the only drugs associated with an increased risk of VTE. The antipsychotics have also been incriminated in the occurrence of venous thromboembolism. The association of thalidomide and dexamethasone, used in the treatment of multiple myeloma, is responsible for a major increase in the risk of VTE. The physiopathological mechanisms accounting for the possible prothrombotic effect of most of these drugs is still not fully understood. Further observational and interventional clinical studies should provide a better understanding of VTE, potentially associated with drugs. However, certain drugs may be associated with a reduced risk of VTE. Although several studies indicate that aspirin and statins may favourably influence the risk of VTE, it is still not possible to draw up any practical recommendations.
Published: 2008

32. Protection against cerebral malaria by the low-molecular-weight thiol pantethine

Author: Marie-France Penet, Nicolas Coltel, Max de Reggi, Mhamad Abou-Hamdan, Emilie Cornille, Georges E. Grau, Bouchra Gharib, Centre de résonance magnétique biologique et médicale (CRMBM), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Unité des Rickettsies et pathogènes émergents (URPE), Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, INSB-INSB-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, INSB-INSB-Centre National de la Recherche Scientifique (CNRS), Neurobiologie des interactions cellulaires et neurophysiopathologie - NICN (NICN), Centre National de la Recherche Scientifique (CNRS)-Université de la Méditerranée - Aix-Marseille 2, Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS), and Université de la Méditerranée - Aix-Marseille 2-Centre National de la Recherche Scientifique (CNRS)
Subjects: Platelet Aggregation, Plasmodium berghei, Pharmacology, MESH: Blood-Brain Barrier, chemistry.chemical_compound, Mice, 0302 clinical medicine, MESH: Animals, MESH: Syndrome, MESH: Platelet Aggregation, Cell Line, Transformed, 0303 health sciences, MESH: Mice, Inbred CBA, Multidisciplinary, MESH: Molecular Weight, Pantethine, Syndrome, Biological Sciences, 3. Good health, medicine.anatomical_structure, Biochemistry, MESH: Platelet Aggregation Inhibitors, Cerebral Malaria, Blood-Brain Barrier, MESH: Permeability, Pantetheine, Platelet aggregation inhibitor, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Female, Malaria, Cerebral, Biology, Blood–brain barrier, MESH: Pantetheine, Permeability, Cell Line, MESH: Malaria, Cerebral, 03 medical and health sciences, Cystamine, medicine, MESH: Plasmodium berghei, Animals, Humans, MESH: Cell Line, Transformed, Platelet activation, MESH: Mice, 030304 developmental biology, MESH: Humans, biology.organism_classification, MESH: Cell Line, Molecular Weight, chemistry, Mice, Inbred CBA, MESH: Female, 030217 neurology & neurosurgery, Platelet Aggregation Inhibitors
Abstract: We report that administration of the low-molecular-weight thiol pantethine prevented the cerebral syndrome in Plasmodium berghei ANKA-infected mice. The protection was associated with an impairment of the host response to the infection, with in particular a decrease of circulating microparticles and preservation of the blood–brain barrier integrity. Parasite development was unaffected. Pantethine modulated one of the early steps of the inflammation–coagulation cascade, i.e., the transbilayer translocation of phosphatidylserine at the cell surface that we demonstrated on red blood cells and platelets. In this, pantethine mimicked the inactivation of the ATP-binding-cassette transporter A1 (ABCA1), which also prevents the cerebral syndrome in this malaria model. However, pantethine acts through a different pathway, because ABCA1 activity was unaffected by the treatment. The mechanisms of pantethine action were investigated, using the intact molecule and its constituents. The disulfide group (oxidized form) is necessary to lower the platelet response to activation by thrombin and collagen. Thio-sensitive mechanisms are also involved in the impairment of microparticle release by TNF-activated endothelial cells. In isolated cells, the effects were obtained by cystamine that lacks the pantothenic moiety of the molecule; however, the complete molecule is necessary to protect against cerebral malaria. Pantethine is well tolerated, and it has already been administered in other contexts to man with limited side effects. Therefore, trials of pantethine treatment in adjunctive therapy for severe malaria are warranted.
Published: 2008

33. High prevalence of undiagnosed patients with peripheral arterial disease in patients hospitalised for non-vascular disorders

Author: Lacroix, Philippe, Aboyans, Victor, Voronin, D., Le Guyader, Alexandre, Cautrès, M., Laskar, Marc, Neuroépidémiologie Tropicale et Comparée (NETEC), Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Université de Limoges (UNILIM), Service de Chirurgie Thoracique et Vasculaire - Médecine vasculaire [CHU Limoges], CHU Limoges, Equipe de Recherche Médicale Appliquée (ERMA), and Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Université de Limoges (UNILIM)-CHU Limoges
Subjects: Adult, Male, MESH: Hospitalization, MESH: Aged, 80 and over, MESH: Cross-Sectional Studies, Prevalence, Humans, MESH: Hydroxymethylglutaryl-CoA Reductase Inhibitors, MESH: Prevalence, Aged, Aged, 80 and over, Peripheral Vascular Diseases, MESH: Aged, MESH: Humans, MESH: Middle Aged, MESH: Peripheral Vascular Diseases, MESH: Adult, Middle Aged, MESH: Male, Hospitalization, body regions, MESH: France, Cross-Sectional Studies, MESH: Platelet Aggregation Inhibitors, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, Hydroxymethylglutaryl-CoA Reductase Inhibitors, MESH: Female, Platelet Aggregation Inhibitors
Abstract: ERMA; International audience; BACKGROUND: Several studies highlight the underestimation of peripheral arterial disease (PAD) rates in general population, leading to a lack of opportunity to detect subjects at a high risk for cardiovascular events. We sought to investigate (i) the prevalence of unrecognised PAD in patients hospitalised for non-vascular diseases and (ii) the intensity of preventive drug therapies in this population. DESIGN AND METHODS: This study was of the cross-sectional design in a tertiary care hospital, which included 291 randomly selected patients of >or=40 years of age. Patients were assessed for medical history, pulse palpation and ankle-brachial index (ABI). The Edinburgh Claudication Questionnaire (ECQ) was administered. PAD was defined either by an ABIor=1.4 or in case of limb revascularisation history. RESULTS: Overall PAD prevalence was 29%; 21 patients (7.2%) with a history of PAD, while 65 (22.3%) had an unknown PAD. Among patients with unknown PAD, a typical intermittent claudication was unusual (3%). In patients without cardiovascular disease (CVD), four factors were associated with unrecognised PAD: absence of posterior tibial pulse (OR 4.49, 95% CI 1.89-10.51; p70 years (OR 2.44, 95% CI 1.07-5.58; p=0.04), CVD risk factors>or=2 (OR 2.63, 95% CI 1.20-5.76; p=0.02). Antiplatelet therapy and statins were each prescribed in 35.5% of the unrecognised PAD patients with ABIor=1.4. CONCLUSIONS: In a tertiary care hospital, the prevalence of unrecognised PAD among patients hospitalised for non-PAD-related causes is high and the preventive CVD therapy rates are low. Hospitalisation is a good opportunity to detect PAD.
Published: 2008

34. Antiplatelet drug use preceding the onset of intracerebral hemorrhage is associated with increased mortality

Author: Romuald Seizeur, Emmanuel Oger, Grégoire Le Gal, Dominique Mottier, Karine Lacut, Gwenaël Prat, Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-Université de Brest (UBO), Centre d'Investigation Clinique (CIC - Brest), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Vision, Action et Gestion d'informations en Santé (VisAGeS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-SIGNAUX ET IMAGES NUMÉRIQUES, ROBOTIQUE (IRISA-D5), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), CentraleSupélec-Télécom Bretagne-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Rennes (ENS Rennes)-Université de Bretagne Sud (UBS)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-CentraleSupélec-Télécom Bretagne-Université de Rennes 1 (UR1), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École normale supérieure - Rennes (ENS Rennes)-Université de Bretagne Sud (UBS)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Service de neurochirurgie [Brest], Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Unité de soins intensifs [Brest], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de Pharmacologie [Rennes], CHU Pontchaillou [Rennes], Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), and Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, MESH: Cerebral Hemorrhage, medicine.medical_specialty, Antiplatelet drug, medicine.medical_treatment, Intermittent pneumatic compression, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, cardiovascular diseases, Intermittent Pneumatic Compression Devices, Aged, Cerebral Hemorrhage, MESH: Intermittent Pneumatic Compression Devices, Venous Thrombosis, Pharmacology, Intracerebral hemorrhage, MESH: Aged, Aspirin, MESH: Humans, MESH: Middle Aged, business.industry, Mortality rate, Middle Aged, medicine.disease, MESH: Male, 3. Good health, nervous system diseases, Venous thrombosis, MESH: Platelet Aggregation Inhibitors, Anesthesia, MESH: Venous Thrombosis, Female, Age of onset, business, MESH: Female, Platelet Aggregation Inhibitors, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract: International audience; Recent studies highlight the contribution of antiplatelet therapy to clinical severity and increased mortality of intracerebral hemorrhage (ICH) but results are discrepant. The aim of this report was to evaluate the association between antiplatelet drug use preceding the onset of ICH and the mortality, assessed at regular intervals, among patients with acute ICH. We analyzed data from a randomized study which enrolled consecutive patients with a documented acute ICH to evaluate the efficacy of intermittent pneumatic compression of the legs in venous thrombosis prevention. Clinical characteristics and treatment used before the onset of ICH were checked at the time of inclusion. Mortality was assessed at regular intervals until 3 months after ICH diagnosis. Among 138 patients included in this report, 30 were current users of antiplatelet therapy at the time of ICH; they were significantly older and less frequently heavy drinkers than non-users of antiplatelet drugs. Mortality rates were 20% at 8 days, 40% at 1 month, and 47% at 3 months among antiplatelet drug users compared with 6.5%, 13% and 19% among non-users. The corresponding estimated risks for mortality related to antiplatelet drug use were 3.6 (95% CI 1.1-12), 4.5 (95% CI 1.8-11), and 3.6 (95% CI 1.5-8.6). Adjusted for age, hypertension and alcohol over use, antiplatelet therapy remained significantly associated with an increased mortality rate of acute ICH. Current antiplatelet drug use preceding the onset of ICH is associated with increased short-term ICH mortality, independently of age.
Published: 2007

35. Influence of omeprazol on the antiplatelet action of clopidogrel associated to aspirin

Author: J. Boschat, M. Gilard, B. Arnaud, G. Le Gal, J. F. Abgrall, Service de Cardiologie (BREST - Cardio), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Optimisation des régulations physiologiques (ORPHY (EA 4324)), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-Université de Brest (UBO)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre d'Investigation Clinique (CIC - Brest), and Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, Deep vein, Coronary Disease, MESH: Aryl Hydrocarbon Hydroxylases, 030204 cardiovascular system & hematology, Gastroenterology, Mixed Function Oxygenases, 0302 clinical medicine, 030212 general & internal medicine, Enzyme Inhibitors, Phosphorylation, MESH: Drug Antagonism, ComputingMilieux_MISCELLANEOUS, MESH: Aged, Aspirin, Acenocoumarol, MESH: Polymorphism, Single Nucleotide, Microfilament Proteins, MESH: Platelet Function Tests, Hematology, Heparin, MESH: Mixed Function Oxygenases, Clopidogrel, 3. Good health, medicine.anatomical_structure, MESH: Platelet Aggregation Inhibitors, MESH: Enzyme Inhibitors, MESH: Cell Adhesion Molecules, Female, Aryl Hydrocarbon Hydroxylases, Drug Antagonism, Omeprazole, medicine.drug, medicine.medical_specialty, Ticlopidine, Platelet Function Tests, MESH: Ticlopidine, MESH: Omeprazole, Polymorphism, Single Nucleotide, MESH: Phosphoproteins, 03 medical and health sciences, MESH: Microfilament Proteins, Internal medicine, medicine, Humans, MESH: Platelet Activation, In patient, MESH: Thrombosis, MESH: Aspirin, Aged, MESH: Angioplasty, MESH: Humans, MESH: Phosphorylation, business.industry, Angioplasty, Thrombosis, Secondary prophylaxis, Phosphoproteins, Platelet Activation, MESH: Male, Cytochrome P-450 CYP2C19, MESH: Protein Processing, Post-Translational, MESH: Coronary Disease, business, Cell Adhesion Molecules, Protein Processing, Post-Translational, Venous thromboembolism, MESH: Female, Platelet Aggregation Inhibitors, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: heparin (Fragmin) in patients with venous thromboembolism andcontraindications to coumarin. Thromb Haemost 1994; 71: 7–11.13 Levine MN, Hirsh J, Horsewood P, Roberts RS, Gent M, Kelton JG.Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin. NEnglJMed1995; 332: 1330–5.14 Pini M, Aiello S, Manotti C, Pattacini C, Quintavalla R, Poli T,Tagliaferri A, Dettori AG. Low-molecular-weight heparin versuswarfarin in the prevention of recurrences after deep vein thrombosis.Thromb Haemost 1994; 72: 191–7.15 Lopaciuk S, Bielska-Falda H, Noszczyk W, Bielawiec M, WitkiewiczW, Filipecki S, Michalak J, Ciesielski L, Mackiewicz Z, Czes-tochowska E, Zawilska K, Cencora A. Low molecular weight heparinversus acenocoumarol in the secondary prophylaxis of deep veinthrombosis. Thromb Haemost 1999; 81: 26–31.16 Santamaria A, Juarez S, Reche A, Gomez-Outes A, Martinez-Gonzalez J, Fontcuberta J, ESFERA Investigators, Low-molecular-weight heparin, bemiparin, in the outpatient treatment and secondaryprophylaxis of venous thromboembolism in standard clinical practice:the ESFERA Study. Int J Clin Pract 2006; 60: 518–25.17 Gomez-Outes A, Rocha E, Martinez Gonzalez J, Kakkar VV. Costeﬀectiveness of bemiparin versus unfractionated heparin and oralanticoagulants in the acute and long-term treatment of deep veinthrombosis. Pharmacoeconomics 2006; 24: 81–92.
Published: 2006

36. Perioperative in-stent thrombosis after lung resection performed within 3 months of coronary stenting

Author: Philippe Boitet, Pierre-Yves Brichon, Jérôme Mouroux, Hans-Beat Ris, Jean-François Velly, Christophe Peillon, Marc Riquet, Antoine Dujon, Service de Chirurgie thoracique, CHU Grenoble, CHU Le Havre, CHU Cedre, Centre Hospitalier Universitaire de Nice (CHU Nice), Service de chirurgie cadiovasculaire et thoracique [Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Hôpital Laennec, Service de chirurgie thoracique, CHU Bordeaux [Bordeaux], Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, and Salas, Danielle
Subjects: Male, MESH: Coronary Thrombosis, Lung Neoplasms, medicine.medical_treatment, Coronary Disease, Postoperative Complications, MESH: Aged, 80 and over, Coronary thrombosis, MESH: Postoperative Period, Carcinoma, Non-Small-Cell Lung, MESH: Postoperative Complications, Myocardial infarction, Postoperative Period, Pneumonectomy, Aged, 80 and over, MESH: Aged, MESH: Middle Aged, General Medicine, Middle Aged, Thrombosis, surgical procedures, operative, MESH: Platelet Aggregation Inhibitors, Platelet aggregation inhibitor, Female, Stents, Cardiology and Cardiovascular Medicine, Pulmonary and Respiratory Medicine, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH: Drug Administration Schedule, MESH: Postoperative Care, Drug Administration Schedule, [SDV.CAN] Life Sciences [q-bio]/Cancer, Angioplasty, medicine, Humans, cardiovascular diseases, Aged, Retrospective Studies, Postoperative Care, MESH: Humans, business.industry, Coronary Thrombosis, MESH: Pneumonectomy, Stent, MESH: Retrospective Studies, Perioperative, medicine.disease, equipment and supplies, Aged Aged, 80 and over Carcinoma, Non-Small-Cell Lung/surgery Coronary Disease/*surgery Coronary Thrombosis/*etiology/prevention & control Drug Administration Schedule Female Humans Lung Neoplasms/surgery Male Middle Aged Platelet Aggregation Inhibitors/administration & dosage *Pneumonectomy Postoperative Care/methods *Postoperative Complications Postoperative Period Retrospective Studies *Stents, MESH: Male, Surgery, MESH: Lung Neoplasms, MESH: Stents, MESH: Coronary Disease, business, MESH: Female, Platelet Aggregation Inhibitors, MESH: Carcinoma, Non-Small-Cell Lung
Abstract: BACKGROUND: Incidence of perioperative in-stent thrombosis associated with myocardial infarction in patients undergoing major lung resection within 3 months of coronary stenting. METHODS: Retrospective multi-institutional trial including all patients undergoing major lung resection (lobectomy or pneumonectomy) within 3 months of coronary stenting with non-drug-eluting stents between 1999 and 2004. RESULTS: There were 32 patients (29 men and 3 women), with age ranging from 46 to 82 years. One, two or four coronary stents were deployed in 72%, 22% and 6% of the patients, respectively. The time intervals between stenting and lung surgery were
Published: 2006

37. [Acute pericarditis: results of a survey of treatment practices of cardiologists]

Author: Jc, Cornily, Le Gal G, Tn, Tram-Lebaillif, Martine Gilard, Boschat J, Jj, Blanc, Calvez, Ghislaine, Service de Cardiologie (BREST - Cardio), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Optimisation des régulations physiologiques (ORPHY (EA 4324)), Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)-Université de Brest (UBO)-Université de Brest (UBO)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)
Subjects: Anti-Inflammatory Agents, Ibuprofen, MESH: Hospitalization, Surveys and Questionnaires, Humans, Pericarditis, Practice Patterns, Physicians', MESH: Aspirin, MESH: Pericarditis, MESH: Physician's Practice Patterns, MESH: Humans, MESH: Middle Aged, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Aspirin, MESH: Questionnaires, Middle Aged, MESH: Ibuprofen, Hospitalization, MESH: France, MESH: Colchicine, MESH: Platelet Aggregation Inhibitors, MESH: Anti-Inflammatory Agents, Acute Disease, MESH: Acute Disease, France, Colchicine, Platelet Aggregation Inhibitors, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; UNLABELLED: Benign acute pericarditis is a common disorder. Although, at first glance, its management appears well defined, the guidelines issued by professional societies with respect to optimal treatment and length of its administration remain vague. METHODS: a brief, anonymous questionnaire probing into treatment practices was sent in April 2005 to all cardiologists of Brittany. RESULTS: we collected 164 analyzable questionnaires out of 248 submitted (66%). The initial investigations in presence of acute pericarditis included an electrocardiogram in 100% of cases, an echocardiogram in 95%, and screening biochemistry in 93% of cases. Systematic hospitalisation was advised by only 24% of cardiologists. Aspirin was prescribed as first choice treatment in 92.5% of cases. Duration of treatment recommendations varied widely, from 21 days by 14% of cardiologists. Hospital-based cardiologists were more likely to systematically hospitalise their patients than outpatient practice-based physicians (79.5% versus 5.1%; p
Published: 2006

38. THE BENEFICIAL EFFECT OF DIETARY ANTIOXIDANT SUPPLEMENTATION ON PLATELET AGGREGATION AND CYCLOSPORINE TREATMENT IN HEART TRANSPLANT RECIPIENTS

Author: Pascale Boissonnat, Georges Dureau, Michel de Lorgeril, Serge Renaud, Jean Ninet, Isabelle Monjaud, J. Guidollet, René Ferrera, Patricia Salen, Claire Monnez, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Cardioprotection, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), and Salen, Patricia
Subjects: Graft Rejection, Male, Platelet Aggregation, medicine.medical_treatment, Lymphocyte, Administration, Oral, 030204 cardiovascular system & hematology, MESH: Cyclosporine, Leukocyte Count, MESH: Vitamin E, 0302 clinical medicine, Vitamin E, Medicine, Platelet, Lymphocytes, Prospective Studies, MESH: Blood Platelets, MESH: Platelet Aggregation, Heart transplantation, 0303 health sciences, MESH: Heart Transplantation, Immunosuppression, 3. Good health, medicine.anatomical_structure, MESH: Platelet Aggregation Inhibitors, Creatinine, MESH: Administration, Oral, Cyclosporine, Blood Platelets, medicine.medical_specialty, Nutritional Supplementation, Diet therapy, MESH: Graft Rejection, MESH: Creatinine, 03 medical and health sciences, MESH: Diet, Internal medicine, Humans, 030304 developmental biology, Transplantation, MESH: Humans, business.industry, MESH: Male, MESH: Prospective Studies, Diet, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Endocrinology, MESH: Leukocyte Count, Heart Transplantation, MESH: Lymphocytes, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Platelet Aggregation Inhibitors, 030217 neurology & neurosurgery
Abstract: International audience; To determine whether dietary antioxidant supplementation can reduce platelet reactivity in heart transplant recipients, 20 patients were prospectively randomized to receive either 500 IU vitamin E orally per day in the form of acetate for 2 months or no vitamin E. Blood creatinine (P = 0.01) and lymphocyte count (P = 0.009) significantly decreased only in supplemented patients, whereas the cyclosporine blood level was not modified. Platelet aggregation was stable in control patients but significantly decreased in supplemented patients in response to either thrombin (from 8.3 +/- 0.9% of maximum aggregation to 3.7 +/- 0.7, P = 0.001) or ADP (secondary wave: from 44.7 +/- 5.9% to 33.2 +/- 7.0, P = 0.02). Thus antioxidant supplementation tended to improve immunosuppression (by reducing lymphocyte count), to reduce cyclosporine nephrotoxicity, and to decrease the high thrombotic risk associated with heart transplantation.
Published: 1994

39. Ticlopidine increases nitric oxide generation in heart-transplant recipients: a possible novel property of ticlopidine

Author: P. Boissonnat, J.-C. Bordet, S. Durbin, J. Delaye, M de Lorgeril, G. Defreyn, Patricia Salen, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Unité de recherche sur l'hémophilie et les maladies hémorragiques constitutionnelles - EA3735, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Laboratoire d'Etudes du Comportement à Long Terme des matériaux de conditionnement (LCLT), Département de recherche sur les Procédés et Matériaux pour les Environnements complexes (DPME), CEA-Direction des Energies (ex-Direction de l'Energie Nucléaire) (CEA-DES (ex-DEN)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-CEA-Direction des Energies (ex-Direction de l'Energie Nucléaire) (CEA-DES (ex-DEN)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Département de recherche sur les technologies pour l'enrichissement, le démantèlement et les déchets (DE2D), and Salen, Patricia
Subjects: Male, Thromboxane, Prostacyclin, 030204 cardiovascular system & hematology, Pharmacology, chemistry.chemical_compound, 0302 clinical medicine, Medicine, Platelet, MESH: Double-Blind Method, MESH: Blood Platelets, 0303 health sciences, Thromboxanes, MESH: Heart Transplantation, MESH: Immunosuppression, 3. Good health, Thromboxane B2, MESH: Platelet Aggregation Inhibitors, Anesthesia, MESH: Endothelium, Vascular, Cardiology and Cardiovascular Medicine, medicine.drug, Blood Platelets, Ticlopidine, MESH: Ticlopidine, MESH: Thromboxanes, MESH: Epoprostenol, Nitric Oxide, Nitric oxide, Excretion, 03 medical and health sciences, Double-Blind Method, MESH: Analysis of Variance, Humans, 030304 developmental biology, Immunosuppression Therapy, Analysis of Variance, MESH: Humans, business.industry, Epoprostenol, MESH: Male, Transplantation, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, chemistry, MESH: Nitric Oxide, Heart Transplantation, Endothelium, Vascular, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Platelet Aggregation Inhibitors
Abstract: International audience; The objective of this study was to evaluate the effects of ticlopidine on the generation of eicosanoids and nitric oxide in heart-transplant recipients. In a randomized double-blind study, we studied the urinary excretion of the stable metabolites of thromboxane, prostacyclin, and nitric oxide before and after ticlopidine (250 mg/day). Platelet aggregation was significantly reduced in ticlopidine-treated patients [from 40.2 +/- 24.2% of maximal aggregation to 14.7 +/- 8.2% in response to adenosine diphosphate (ADP); p < 0.001] but not in the placebo group, confirming the efficacy of the drug with that dosage in these specific patients. The 24-h urinary excretion of prostacyclin metabolites was not modified by ticlopidine (1,865 +/- 833 ng/24 h at day 14 and 1,664 +/- 425 ng/24 h at day 0), whereas the excretion of thromboxane B2 tended to increase in the ticlopidine group (from 3,854 +/- 1,163 ng/24 h at day 0 to 5,014 +/- 2,914 ng/24 h at day 14), although not significantly. The excretion of nitric oxide metabolites (although not different from that of healthy nonimmunosuppressed subjects) was significantly (p < 0.005) increased in the ticlopidine group (from 3,082 +/- 1,683 micromol/24 h at day 0 to 4,133 +/- 2,262 micromol/24 h at day 14), but not in controls. Thus ticlopidine does not reduce prostacyclin but increases the systemic generation of nitric oxide, both substances having major antiplatelet and vasodilator properties. Further studies are warranted to examine whether ticlopidine could reduce the incidence of thromboembolic complications in these patients and whether this possible novel property of ticlopidine is restricted to immunosuppressed heart-transplant recipients.
Published: 1998

40. A drug interaction study between ticlopidine and cyclosporin in heart transplant recipients

Author: E. Serres, M. de Lorgeril, Patricia Salen, R. Brouard, J. C. Barthelemy, A. M. Batt, V. Perroux, P. Boissonnat, J. Delaye, Salen, Patricia, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM ), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM), CECA-ATOCHEM, Laboratoire d'Etudes du Comportement à Long Terme des matériaux de conditionnement (LCLT), Département de recherche sur les technologies pour l'enrichissement, le démantèlement et les déchets (DE2D), CEA-Direction des Energies (ex-Direction de l'Energie Nucléaire) (CEA-DES (ex-DEN)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-CEA-Direction des Energies (ex-Direction de l'Energie Nucléaire) (CEA-DES (ex-DEN)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), and Département de recherche sur les Procédés et Matériaux pour les Environnements complexes (DPME)
Subjects: Male, Hydrocortisone, MESH: Drug Interactions, 030204 cardiovascular system & hematology, Pharmacology, MESH: Cyclosporine, Mixed Function Oxygenases, 0302 clinical medicine, Cytochrome P-450 Enzyme System, Oral administration, Cyclosporin a, Medicine, Cytochrome P-450 CYP3A, Pharmacology (medical), Drug Interactions, MESH: Double-Blind Method, 030212 general & internal medicine, Prospective Studies, MESH: Aged, MESH: Middle Aged, MESH: Heart Transplantation, General Medicine, Middle Aged, MESH: Mixed Function Oxygenases, MESH: Hydrocortisone, 3. Good health, Tolerability, MESH: Platelet Aggregation Inhibitors, MESH: Cytochrome P-450 Enzyme System, Cyclosporine, MESH: Immunosuppressive Agents, Immunosuppressive Agents, medicine.drug, Adult, Ticlopidine, Adolescent, MESH: Ticlopidine, 03 medical and health sciences, Pharmacokinetics, Double-Blind Method, MESH: Analysis of Variance, Humans, Aged, MESH: Adolescent, Analysis of Variance, MESH: Humans, business.industry, MESH: Adult, Drug interaction, Ciclosporin, MESH: Male, MESH: Prospective Studies, Transplantation, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Heart Transplantation, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Platelet Aggregation Inhibitors
Abstract: Objectives: Previous uncontrolled studies have suggested an interaction between ticlopidine, a major antiplatelet agent, and cyclosporin in heart- and kidney-transplant recipients. The aims of this study were to examine in a randomised, double-blind fashion, the possible interaction between cyclosporin A and ticlopidine (250 mg per day) and the tolerability of this combination in heart-transplant recipients. Methods: Twenty heart-transplant recipients were randomised into either a treated or a placebo group. Blood samples were drawn for time-course evaluation of cyclosporin blood levels over a period of 12 h, following the morning intake of cyclosporin and, for platelet aggregation studies, before and after 14 days of ticlopidine administration. Twenty four-hour urine samples were collected for 6-β-hydroxycortisol measurements, before and after 14 days of ticlopidine. Results: Although given at half the recommended daily dosage, ticlopidine significantly reduced platelet aggregation. Pharmacokinetic parameters indicate that the bioavailability of cyclosporin A was not significantly modified by ticlopidine. However, one patient in the ticlopidine group was withdrawn because of a major fall in cyclosporin blood level within 3 days of treatment. Urinary excretion of 6-β-hydroxycortisol was augmented after treatment in the ticlopidine group compared with the placebo group, suggesting that induction of drug metabolism might have occurred. Data also show quite a large intra-individual variability in cyclosporin bioavailability in the placebo group, suggesting that poor absorption of the drug formulation and/or poor compliance might have contributed to the decreased cyclosporin blood levels in the patient withdrawn from this study and in previous uncontrolled studies. Conclusion: Cyclosporin bioavailability was not clearly modified by a half dosage of ticlopidine in this study. We, however, recommend closely monitoring cyclosporin blood levels when prescribing ticlopidine. Further studies will be needed with new formulations of cyclosporin or when using the full dosage of ticlopidine.
Published: 1997

41. Study on the binding of lactotransferrin (lactoferrin) to human PHA-activated lymphocytes and non-activated platelets. Localisation and description of the receptor-binding site

Author: Mazurier, J., Legrand, D., Leveugle, B., Rochard, E., Montreuil, J., Spik, G., Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 (UGSF), Institut National de la Recherche Agronomique (INRA)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), and Université de Lille-Centre National de la Recherche Scientifique (CNRS)
Subjects: Blood Platelets, Models, Molecular, Platelet Aggregation, Molecular Sequence Data, MESH: Protein Structure, Secondary, MESH: Binding, Competitive, Receptors, Cell Surface, MESH: Amino Acid Sequence, Lymphocyte Activation, Binding, Competitive, MESH: Phytohemagglutinins, Protein Structure, Secondary, Iodine Radioisotopes, Humans, MESH: Lysine, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Amino Acid Sequence, Lymphocytes, Phytohemagglutinins, MESH: Peptide Fragments, MESH: Lymphocyte Activation, MESH: Blood Platelets, MESH: Platelet Aggregation, MESH: Receptors, Cell Surface, MESH: Molecular Sequence Data, MESH: Humans, MESH: Adenosine Diphosphate, MESH: Kinetics, Lysine, Cell Membrane, MESH: Iodine Radioisotopes, MESH: Lactoferrin, Peptide Fragments, Adenosine Diphosphate, Kinetics, Lactoferrin, MESH: Platelet Aggregation Inhibitors, MESH: Lymphocytes, MESH: Models, Molecular, Platelet Aggregation Inhibitors, MESH: Cell Membrane
Abstract: International audience; Fluorescein isothiocyanate derivatization of human lactotransferrin on Lys-264 as well as covalent addition of sulfosuccinimidyl 2-(p-azidosalicylamido)ethyl-1,3'- dithiopropionate (SASD)* on Lys-74 inhibits the binding of the glycoprotein to both human PHA-activated lymphocytes and non-activated platelets. This suggests that the cell binding site of lactotransferrin is located in the vicinity of the lysine residues 74 & 264 and does not occur either through electrostatic or lectin interactions. In contrast, the derivatization of lactotransferrin using sulfosuccinimidyl 6-(4'-azido-2'-nitrophenyl-amino) hexanoate (sulfo-SANPAH), on Lys-281 does not modify the binding parameters of lactotransferrin to the cells. Molecular modeling showed the position of SASD, sulfo-SANPAH and fluorescein molecules at the surface of the protein and suggested that SASD and fluorescein could mask the two loop-containing regions of human lactotransferrin (residues 28-34 and 38-45). Elsewhere, a 6 kDa peptide covering the peptide chain from residues 4 to 52 was isolated and its inhibitory effect on the binding of lactotransferrin to both human PHA-activated lymphocytes and non-activated platelets was demonstrated. Inhibition of ADP-induced platelet aggregation by lactotransferrin (50% inhibition = 10 nM) was also found with the N-t fragment of lactotransferrin (residues 3-281; 50% inhibition = 2 microM) and with two synthetic peptides: KRDS tetrapeptide (50% inhibition = 350 microM) and CFQWQRNMRKVRGPPVSC octodecapeptide (50% inhibition = 20 microM) corresponding to the lactotransferrin amino acid sequence 39-42 and 20-37, respectively.
Published: 1994

42. Lactotransferrin binding to its platelet receptor inhibits platelet aggregation

Author: Dominique Legrand, Béatrice Leveugle, Geneviève Spik, Jean Montreuil, Claudine Mazurier, Joël Mazurier, Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 (UGSF), Institut National de la Recherche Agronomique (INRA)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), and Université de Lille-Centre National de la Recherche Scientifique (CNRS)
Subjects: Platelet Aggregation, Molecular Sequence Data, MESH: Rabbits, Receptors, Cell Surface, Platelet Membrane Glycoproteins, MESH: Amino Acid Sequence, Platelet membrane glycoprotein, Biochemistry, 03 medical and health sciences, chemistry.chemical_compound, MESH: Lectins, Cell surface receptor, Lectins, Leukocyte degranulation, Animals, Humans, MESH: Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Amino Acid Sequence, Binding site, Fluorescein isothiocyanate, MESH: Peptide Fragments, 030304 developmental biology, MESH: Receptors, Cell Surface, MESH: Platelet Aggregation, 0303 health sciences, MESH: Humans, MESH: Molecular Sequence Data, biology, Tetrapeptide, MESH: Adenosine Diphosphate, Lactoferrin, Chemistry, 030302 biochemistry & molecular biology, MESH: Platelet Membrane Glycoproteins, Molecular biology, Peptide Fragments, MESH: Lactoferrin, 3. Good health, Lactotransferrin, Adenosine Diphosphate, MESH: Platelet Aggregation Inhibitors, biology.protein, Rabbits, Platelet Aggregation Inhibitors
Abstract: International audience; A fluorescent lactotransferrin probe was prepared by coupling 5-(([2-(carbhydrazino)methyl]-thio)acetyl)amino fluorescein to aldehyde groups that were produced by a mild periodic-acid oxidation of the glycan moieties of lactotransferrin. In this manner, the receptor-binding site of the lactotransferrin remains active in contrast to the binding site of the lactotransferrin derivatized with fluorescein isothiocyanate. The fluorescent probe allowed us to characterize, by flow cytometry, the binding of lactotransferrin to non-activated human platelets. The putative lactotransferrin platelet receptor was purified and its immunological and physico-chemical properties were found to be very similar to those of the receptor previously isolated from activated human lymphocytes. Lactotransferrin inhibits ADP-induced platelet aggregation at concentrations down to 5 nM, which can be reached in the plasma after leukocyte degranulation. Inhibition of platelet aggregation was also observed with the N-terminal fragment of lactotransferrin (residues 3-281; 50% inhibition = 2 microM) and with CFQWQRNMRKVRGPPVSC synthetic octodecapeptide (residues 20-37; 50% inhibition = 20 microM) corresponding to one of the two external loops (residues 28-34 and 39-42) where we recently located the receptor-binding site. The activity (50% inhibition = 500 microM) of the tetrapeptide KRDS (residues 39-42), which has already been described, was at least 25-times and 16000-times lower than the activity of the octodecapeptide and of the lactotransferrin molecules, respectively. Finally, the inhibition was demonstrated to be mediated by a mechanism which requires the binding of lactotransferrin to its putative receptor and not to platelet glycoprotein IIb-IIIa.
Published: 1993

43. High prevalence of thromoembolic complications in heart transplant recipients. Which preventive strategy.?

Author: P. Boissonnat, Adeleine P, Georges Dureau, René Ferrera, R. Forrat, de Lorgeril M, Jean Ninet, De Lorgeril, Michel, Cardioprotection, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), and VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)
Subjects: Adult, Male, Pediatrics, medicine.medical_specialty, Adolescent, Thrombophlebitis, Sudden death, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Thromboembolism, MESH: Child, Antithrombotic, medicine, Prevalence, Humans, Child, Stroke, MESH: Prevalence, Aged, Retrospective Studies, MESH: Adolescent, MESH: Aged, Transplantation, High prevalence, MESH: Humans, MESH: Middle Aged, Vascular disease, business.industry, MESH: Child, Preschool, MESH: Heart Transplantation, MESH: Adult, MESH: Retrospective Studies, Middle Aged, medicine.disease, MESH: Male, Surgery, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, MESH: Platelet Aggregation Inhibitors, MESH: Thromboembolism, Child, Preschool, Heart Transplantation, Female, Complication, business, MESH: Female, Platelet Aggregation Inhibitors
Abstract: International audience; Consecutive patients transplanted between January 1984 and December 1988 were followed until August 1992 to detect fatal and nonfatal thromboembolic complications, including sudden death, acute and chronic myocardial infarction, pulmonary and peripheral embolisms, stroke, and thrombophlebitis. The probability of developing such complications was 9.86 per 100 patients per year. The probability of fatal complications was 3.97% per year; the mean interval between transplant and death was 1247 days versus 29.5 days for nonthromboembolic deaths. Thromboembolic deaths represented 5.1% of total mortality at the first year posttransplant but 57, 30, 67 and 73% at the second, third, fourth, and fifth years, respectively. Among the prognosis factors that were analyzed, none was significant predictor of thromboembolic complication. This high prevalence of thromboembolic complications suggests that effective antithrombotic strategy should be defined in heart transplant recipients.

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