25 results on '"Aspirin/administration & dosage"'
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2. Aspirine en prévention cardiovasculaire primaire : la fin d’une époque ? [Aspirin for primary cardiovascular prevention : the end of an era ?]
- Author
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Ravach, G., Fournier, S., Mazzolai, L., and Nanchen, D.
- Subjects
Aspirin/administration & dosage ,Aspirin/therapeutic use ,Cardiovascular Diseases/prevention & control ,Hemorrhage/chemically induced ,Humans ,Primary Prevention/methods ,Primary Prevention/trends ,Risk Assessment - Abstract
Low-dose aspirin in primary prevention of cardiovascular disease is still debated. Recent clinical trials of aspirin vs placebo reported an unfavourable risk-benefit ratio with an increase in major bleedings without reduction on the occurrence of non-fatal cardiovascular events. These studies also highlight that current cardiovascular risk calculators overestimate cardiovascular risk, which is probably related to the improvement in the management of cardiovascular risk factors over the last decades. In accordance with European cardiovascular prevention recommendations, aspirin should not be prescribed for the primary prevention of cardiovascular disease.
- Published
- 2020
3. Dual Antiplatelet or Dual Antithrombotic Therapy for Secondary Prevention in High-Risk Patients with Stable Coronary Artery Disease?
- Author
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Sumaya, Wael, Geisler, Tobias, Kristensen, Steen D, and Storey, Robert F
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Male ,Risk ,Platelet Aggregation Inhibitors/therapeutic use ,Coronary Artery Disease/drug therapy ,Rivaroxaban/administration & dosage ,Decision Making ,LOW-DOSE RIVAROXABAN ,dual antithrombotic therapy ,Purinergic P2Y Receptor Antagonists/therapeutic use ,Myocardial Ischemia/drug therapy ,ticagrelor ,Secondary Prevention/methods ,Acute Coronary Syndrome/drug therapy ,ATHEROTHROMBOTIC EVENTS ,PRASUGREL ,Humans ,cardiovascular diseases ,CARDIOVASCULAR EVENTS ,Aspirin/administration & dosage ,rivaroxaban ,Stroke/prevention & control ,Aged ,Fibrinolytic Agents/therapeutic use ,2017 ESC ,Ticagrelor/administration & dosage ,Middle Aged ,dual antiplatelet therapy ,ASPIRIN ,MYOCARDIAL-INFARCTION ,CLOPIDOGREL ,Myocardial Infarction/prevention & control ,PLATELET INHIBITION ,Female ,Cardiovascular Diseases/prevention & control ,coronary artery disease ,Algorithms - Abstract
Antithrombotic treatment is a key component of secondary prevention following acute coronary syndromes (ACS). Although dual antiplatelet therapy is standard therapy post-ACS, duration of treatment is the subject of ongoing debate. Prolonged dual antiplatelet therapy in high-risk patients with history of myocardial infarction reduced the risk of recurrent myocardial infarction, stroke or cardiovascular death. Similarly, in patients with stable coronary artery disease, two-thirds of whom had a history of myocardial infarction, dual antithrombotic therapy with very-low-dose rivaroxaban and aspirin also resulted in improved ischaemic outcomes. In the absence of head-to-head comparison, choosing the most appropriate treatment strategy can be challenging, particularly when it comes to balancing the risks of ischaemia and bleeding. We aim to review the evidence for currently available antithrombotic treatments and provide a practical algorithm to aid the decision-making process.
- Published
- 2019
4. Two common mild analgesics have no effect on general endocrine mediated endpoints in zebrafish (Danio rerio)
- Author
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Poul Bjerregaard, Birgit Lund, Jane Ebsen Morthorst, and Henrik Holbech
- Subjects
0301 basic medicine ,Anti-Inflammatory Agents, Non-Steroidal/administration & dosage ,Physiology ,Health, Toxicology and Mutagenesis ,Endocrine Disruptors ,Pharmacology ,Toxicology ,Biochemistry ,Larva/drug effects ,Vitellogenins ,chemistry.chemical_compound ,Acetaminophen/administration & dosage ,Sexual maturity ,Analgesics, Non-Narcotic/administration & dosage ,Prostaglandin E2 ,Zebrafish ,biology ,Anti-Inflammatory Agents, Non-Steroidal ,digestive, oral, and skin physiology ,Gene Expression Regulation, Developmental ,General Medicine ,Analgesics, Non-Narcotic ,Larva ,medicine.drug ,animal structures ,Danio ,Prostaglandin ,Ovum/drug effects ,03 medical and health sciences ,Vitellogenin ,medicine ,Animals ,Endocrine system ,Sex Ratio ,Aspirin/administration & dosage ,Acetaminophen ,Ovum ,Aspirin ,Dose-Response Relationship, Drug ,Gene Expression Regulation, Developmental/drug effects ,business.industry ,Vitellogenins/genetics ,Cell Biology ,biology.organism_classification ,030104 developmental biology ,chemistry ,Prostaglandins ,biology.protein ,Prostaglandins/metabolism ,business - Abstract
Mild analgesics such as acetylsalicylic acid (ASA) and acetaminophen (APAP) exert their pain-relieving effect in humans by inhibition of prostaglandin synthesis. Prostaglandins play key roles in developmental and reproductive processes in vertebrates, and in recent years, it has been suggested that weak analgesics might also act as endocrine disrupters. In a set of experiments we investigated if ASA and APAP affect well-established endocrine endpoints in zebrafish (Danio rerio), which is a commonly used model organism in the investigation of endocrine disrupting chemicals. Zebrafish were exposed to APAP (0.22, 2.3, and 30 mg L − 1) or ASA (0.2, 0.5, 1.7, and 8.2 mg L − 1) from hatch to sexual maturity in a test design resembling the OECD Fish Sexual Development Test. No effects on sex ratio and vitellogenin levels were observed. Adult zebrafish were exposed to high concentrations (mg L − 1) of ASA or APAP for eight or 14 days. ASA reduced the levels of prostaglandin E 2, but had no effect on the concentration of 11-ketotestosterone and vitellogenin. Overall, ASA decrease prostaglandin E 2 concentrations, but well-established endpoints for endocrine disruption in zebrafish are generally not affected by aquatic exposure neither during development nor adulthood. According to the WHO/IPCS definition of an endocrine disrupter, the present results do not define APAP and ASA as endocrine disrupters.
- Published
- 2018
5. Rivaroxaban with or without aspirin in patients with stable peripheral or carotid artery disease: an international, randomised, double-blind, placebo-controlled trial
- Author
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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
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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.
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- 2018
6. Use of Low-Dose Aspirin and Mortality After Prostate Cancer Diagnosis:A Nationwide Cohort Study
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Background: Recent studies suggest that aspirin use may improve survival in patients with prostate cancer.Objective: To assess the association between postdiagnosis use of low-dose aspirin and prostate cancer mortality.Design: Nationwide cohort study.Setting: Denmark.Patients: Men with incident prostate adenocarcinoma between 2000 and 2011.Measurements: Nationwide registry data on tumor characteristics, drug use, primary prostate cancer therapy, comorbidity, and socioeconomic parameters. Postdiagnosis use of low-dose aspirin (75 to 150 mg) was defined as 2 or more prescriptions filled within 1 year after prostate cancer diagnosis. Follow-up started 1 year after prostate cancer diagnosis. In secondary analyses, low-dose aspirin use was assessed within exposure periods of 5 or 7.5 years after prostate cancer diagnosis.Results: Of 29 136 patients (median age, 70 years), 7633 died of prostate cancer and 5575 died of other causes during a median follow-up of 4.9 years (interquartile range, 3.1 to 7.2 years), through 2015. Postdiagnosis low-dose aspirin use was associated with adjusted hazard ratios (HRs) of 0.95 (95% CI, 0.89 to 1.01) for prostate cancer-specific mortality and 1.12 (CI, 1.05 to 1.20) for other-cause mortality. The secondary analyses showed that prostate cancer mortality was slightly reduced with low-dose aspirin use after the 5-year (HR, 0.91 [CI, 0.83 to 1.01]) and 7.5-year (HR, 0.84 [CI, 0.72 to 0.97]) postdiagnosis exposure periods, notably among patients filling prescriptions for a large quantity of low-dose aspirin tablets during the 7.5-year period.Limitations: Data on over-the-counter aspirin use were unavailable. Some residual confounding was possible as a result of incomplete data on some prognostic factors.Conclusion: The study did not support an overall effect of postdiagnosis low-dose aspirin use on prostate cancer mortality. However, results for extended exposure periods suggest that
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- 2019
7. Contemporary Treatment of Unstable Angina and Non-ST-Segment-Elevation Myocardial Infarction (Part 2).
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Sami, Shehzad and Willerson, James T.
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CORONARY disease , *MYOCARDIAL infarction , *ANGINA pectoris , *ANGIOPLASTY , *ANGIOTENSIN converting enzyme , *CLOPIDOGREL , *HEPARIN - Abstract
In Part 1 of this review, we discussed how plaque rupture is the most common underlying cause of most cases of unstable angina/non-ST-segment-elevation myocardial infarction (UA/NSTEMI) and how early risk stratification is vital for the timely diagnosis and treatment of acute coronary syndromes (ACS). Now, in Part 2, we focus on the medical therapies and treatment strategies (early conservative vs early invasive) used for UA/NSTEMI. We also discuss results from various large randomized controlled trials that have led to the contemporary standards of practice for, and reduced morbidity and death from, UA/NSTEMI. In summary, ACS involving UA/NSTEMI is associated with high rates of adverse cardiovascular events, despite recent therapeutic advances. Plaque composition and inflammation are more important in the pathogenesis of ACS than is the actual degree of arterial stenosis. As results from new trials challenge our current practices and help us develop the optimal treatment strategy for UA/NSTEMI patients, the cornerstones of contemporary treatment remain early risk stratification and aggressive medical therapy, supplemented by coronary angiography in appropriately selected patients. An early-invasive-treatment strategy is of most benefit to high-risk patients, whereas an early-conservative strategy is recommended for low-risk patients. Adjunctive medical therapy with acetylsalicylic acid, clopidogrel or another adenosine diphosphate antagonist, glycoprotein IIb/IIIa inhibitors, and either low-molecular-weight heparin or unfractionated heparin, in the appropriate setting, further reduces the risk of ischemic events secondary to thrombosis. Short- and long-term inhibition of platelet aggregation should be achieved by appropriately evaluating the risk of bleeding complications in these patients. [ABSTRACT FROM AUTHOR]
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- 2010
8. PRIMMO study protocol
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Emiel De Jaeghere, Hannelore Denys, Katrien Vandecasteele, Sandra Tuyaerts, Peter Vuylsteke, Sandrine Aspeslagh, Frédéric Amant, Peter van Dam, Lien Lippens, Eline Naert, Alex De Caluwé, An M. T. Van Nuffel, Piet Dirix, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service d'oncologie médicale, Physiology, Faculty of Medicine and Pharmacy, Medical Oncology, Laboratory for Medical and Molecular Oncology, Faculty of Physical Education and Physical Therapy, ARD - Amsterdam Reproduction and Development, CCA - Cancer Treatment and Quality of Life, CCA - Cancer biology and immunology, and AII - Cancer immunology
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0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_treatment ,Immune modulation ,Drug repurposing ,PD-1 blockade ,Uterine Cervical Neoplasms ,MICROENVIRONMENT ,Pembrolizumab ,THERAPY ,Cyclophosphamide/administration & dosage ,Uterine sarcoma ,Study Protocol ,0302 clinical medicine ,Medicine and Health Sciences ,Medicine ,Lansoprazole/administration & dosage ,Vitamin D ,Radiation ,Neoplasm Recurrence, Local/therapy ,Abscopal effect ,Sarcoma ,Chemoradiotherapy ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,D-3 TREATMENT ,Vitamin D/administration & dosage ,Antineoplastic Agents/administration & dosage ,Treatment Outcome ,Tumor microenvironment ,030220 oncology & carcinogenesis ,Female ,Immunotherapy ,Endometrial Neoplasms/therapy ,Biologie ,Antibodies, Monoclonal, Humanized/administration & dosage ,RADIOTHERAPY ,medicine.medical_specialty ,Curcumin ,Curcumin/administration & dosage ,Antineoplastic Agents ,Endometrial carcinoma ,Antibodies, Monoclonal, Humanized ,lcsh:RC254-282 ,Financial toxicity ,03 medical and health sciences ,Uterine cancer ,Internal medicine ,Genetics ,Humans ,Sarcoma/therapy ,Lansoprazole ,HEAD ,IMMUNOTHERAPY ,Aspirin/administration & dosage ,PEMBROLIZUMAB ,Cyclophosphamide ,Cervical carcinoma ,Aspirin ,business.industry ,Metronomic chemotherapy ,Drug Repositioning ,medicine.disease ,Metronomic Chemotherapy ,Survival Analysis ,Immune checkpoint ,Blockade ,Endometrial Neoplasms ,Cancérologie ,030104 developmental biology ,CELLS ,Human medicine ,Neoplasm Recurrence, Local ,business ,Uterine Cervical Neoplasms/therapy ,RESISTANCE ,RESPONSES - Abstract
Background: Immunotherapeutic approaches have revolutionized oncological practice but are less evaluated in gynecological malignancies. PD-1/PD-L1 blockade in gynecological cancers showed objective responses in 13-17% of patients. This could be due to immunosuppressive effects exerted by gynecological tumors on the microenvironment and an altered tumor vasculature. In other malignancies, combining checkpoint blockade with radiation delivers benefit that is believed to be due to the abscopal effect. Addition of immune modulation agents has also shown to enhance immune checkpoint blockade efficacy. Therefore we designed a regimen consisting of PD-1 blockade combined with radiation, and different immune/environmental-targeting compounds: repurposed drugs, metronomic chemotherapy and a food supplement. We hypothesize that these will synergistically modulate the tumor microenvironment and induce and sustain an anti-tumor immune response, resulting in tumor regression. Methods: PRIMMO is a multi-center, open-label, non-randomized, 3-cohort phase 2 study with safety run-in in patients with recurrent/refractory cervical carcinoma, endometrial carcinoma or uterine sarcoma. Treatment consists of daily intake of vitamin D, lansoprazole, aspirin, cyclophosphamide and curcumin, starting 2 weeks before the first pembrolizumab dose. Pembrolizumab is administered 3-weekly for a total of 6 cycles. Radiation (3 × 8 Gy) is given on days 1, 3 and 5 of the first pembrolizumab dose. The safety run-in consists of 6 patients. In total, 18 and 25 evaluable patients for cervical and endometrial carcinoma respectively are foreseen to enroll. No sample size is determined for uterine sarcoma due to its rarity. The primary objective is objective response rate at week 26 according to immune-related response criteria. Secondary objectives include safety, objective response rate at week 26 according to RECIST v1.1, best overall response, progression-free survival, overall survival and quality of life. Exploratory, translational research aims to evaluate immune biomarkers, extracellular vesicles, cell death biomarkers and the gut microbiome. Discussion: In this study, a combination of PD-1 blockade, radiation and immune/environmental-targeting compounds is tested, aiming to tackle the tumor microenvironment and induce anti-tumor immunity. Translational research is performed to discover biomarkers related to the mode of action of the combination. Trial registration: EU Clinical Trials Register: EudraCT 2016-001569-97, registered on 19-6-2017. Clinicaltrials.gov: NCT03192059, registered on 19-6-2017., SCOPUS: ar.j, info:eu-repo/semantics/published
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- 2019
9. Dabigatran for Prevention of Stroke after Embolic Stroke of Undetermined Source
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Diener, Hc, Sacco, Rl, Easton, Jd, Granger, Cb, Bernstein, Ra, Uchiyama, S, Kreuzer, J, Cronin, L, Cotton, D, Grauer, C, Brueckmann, M, Chernyatina, M, Donnan, G, Ferro, Jm, Grand, M, Kallmunzer, B, Krupinski, J, Lee, Bc, Lemmens, R, Masjuan, J, Odinak, M, Saver, Jl, Schellinger, Pd, Toni, D, Toyoda, K, RE-SPECT ESUS Steering Committee and Investigators, Tassi, R, Cardiology, and ACS - Heart failure & arrhythmias
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Male ,Stroke/etiology ,medicine.medical_specialty ,Aged ,Antithrombins ,Aspirin ,Dabigatran ,Double-Blind Method ,Female ,Hemorrhage ,Humans ,Incidence ,Intracranial Embolism ,Kaplan-Meier Estimate ,Middle Aged ,Platelet Aggregation Inhibitors ,Recurrence ,Secondary Prevention ,Stroke ,Medizin ,030204 cardiovascular system & hematology ,Antithrombins/administration & dosage ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Hemorrhage/chemically induced ,Intracranial Embolism/drug therapy ,medicine ,Dabigatran/administration & dosage ,030212 general & internal medicine ,Aspirin/administration & dosage ,Platelet Aggregation Inhibitors/administration & dosage ,Rivaroxaban ,business.industry ,Hazard ratio ,Warfarin ,Atrial fibrillation ,General Medicine ,medicine.disease ,Platelet aggregation inhibitor ,business ,medicine.drug - Abstract
BACKGROUND: Cryptogenic strokes constitute 20 to 30% of ischemic strokes, and most cryptogenic strokes are considered to be embolic and of undetermined source. An earlier randomized trial showed that rivaroxaban is no more effective than aspirin in preventing recurrent stroke after a presumed embolic stroke from an undetermined source. Whether dabigatran would be effective in preventing recurrent strokes after this type of stroke was unclear. METHODS: We conducted a multicenter, randomized, double-blind trial of dabigatran at a dose of 150 mg or 110 mg twice daily as compared with aspirin at a dose of 100 mg once daily in patients who had had an embolic stroke of undetermined source. The primary outcome was recurrent stroke. The primary safety outcome was major bleeding. RESULTS: A total of 5390 patients were enrolled at 564 sites and were randomly assigned to receive dabigatran (2695 patients) or aspirin (2695 patients). During a median follow-up of 19 months, recurrent strokes occurred in 177 patients (6.6%) in the dabigatran group (4.1% per year) and in 207 patients (7.7%) in the aspirin group (4.8% per year) (hazard ratio, 0.85; 95% confidence interval [CI], 0.69 to 1.03; P = 0.10). Ischemic strokes occurred in 172 patients (4.0% per year) and 203 patients (4.7% per year), respectively (hazard ratio, 0.84; 95% CI, 0.68 to 1.03). Major bleeding occurred in 77 patients (1.7% per year) in the dabigatran group and in 64 patients (1.4% per year) in the aspirin group (hazard ratio, 1.19; 95% CI, 0.85 to 1.66). Clinically relevant nonmajor bleeding occurred in 70 patients (1.6% per year) and 41 patients (0.9% per year), respectively. CONCLUSIONS: In patients with a recent history of embolic stroke of undetermined source, dabigatran was not superior to aspirin in preventing recurrent stroke. The incidence of major bleeding was not greater in the dabigatran group than in the aspirin group, but there were more clinically relevant nonmajor bleeding events in the dabigatran group. (Funded by Boehringer Ingelheim; RE-SPECT ESUS ClinicalTrials.gov number, NCT02239120.).
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- 2019
10. Use of low-dose aspirin and mortality after prostate cancer diagnosis:A nationwide cohort study
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Mette Nørgaard, Anton Pottegård, Michael Borre, Henrik Toft Sørensen, Charlotte Skriver, Klaus Brasso, Susanne Oksbjerg Dalton, Signe Benzon Larsen, Søren Friis, Jesper Hallas, and Christian Dehlendorff
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Adult ,Male ,medicine.medical_specialty ,Anti-Inflammatory Agents, Non-Steroidal/administration & dosage ,Denmark ,Adenocarcinoma ,01 natural sciences ,Cohort Studies ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,Prostate ,Interquartile range ,Risk Factors ,Internal medicine ,Cause of Death ,Internal Medicine ,medicine ,Humans ,030212 general & internal medicine ,Registries ,0101 mathematics ,Age of Onset ,Aspirin/administration & dosage ,Aged ,Proportional Hazards Models ,Aged, 80 and over ,Prostatic Neoplasms/diagnosis ,Aspirin ,Proportional hazards model ,business.industry ,010102 general mathematics ,Hazard ratio ,Anti-Inflammatory Agents, Non-Steroidal ,Cancer ,Prostatic Neoplasms ,General Medicine ,Middle Aged ,medicine.disease ,Denmark/epidemiology ,medicine.anatomical_structure ,Adenocarcinoma/diagnosis ,Neoplasm Grading ,business ,Cohort study ,medicine.drug - Abstract
Background: Recent studies suggest that aspirin use may improve survival in patients with prostate cancer.Objective: To assess the association between postdiagnosis use of low-dose aspirin and prostate cancer mortality.Design: Nationwide cohort study.Setting: Denmark.Patients: Men with incident prostate adenocarcinoma between 2000 and 2011.Measurements: Nationwide registry data on tumor characteristics, drug use, primary prostate cancer therapy, comorbidity, and socioeconomic parameters. Postdiagnosis use of low-dose aspirin (75 to 150 mg) was defined as 2 or more prescriptions filled within 1 year after prostate cancer diagnosis. Follow-up started 1 year after prostate cancer diagnosis. In secondary analyses, low-dose aspirin use was assessed within exposure periods of 5 or 7.5 years after prostate cancer diagnosis.Results: Of 29 136 patients (median age, 70 years), 7633 died of prostate cancer and 5575 died of other causes during a median follow-up of 4.9 years (interquartile range, 3.1 to 7.2 years), through 2015. Postdiagnosis low-dose aspirin use was associated with adjusted hazard ratios (HRs) of 0.95 (95% CI, 0.89 to 1.01) for prostate cancer-specific mortality and 1.12 (CI, 1.05 to 1.20) for other-cause mortality. The secondary analyses showed that prostate cancer mortality was slightly reduced with low-dose aspirin use after the 5-year (HR, 0.91 [CI, 0.83 to 1.01]) and 7.5-year (HR, 0.84 [CI, 0.72 to 0.97]) postdiagnosis exposure periods, notably among patients filling prescriptions for a large quantity of low-dose aspirin tablets during the 7.5-year period.Limitations: Data on over-the-counter aspirin use were unavailable. Some residual confounding was possible as a result of incomplete data on some prognostic factors.Conclusion: The study did not support an overall effect of postdiagnosis low-dose aspirin use on prostate cancer mortality. However, results for extended exposure periods suggest that low-dose aspirin use might be inversely associated with prostate cancer mortality after 5 years from cancer diagnosis.Primary Funding Source: Danish Cancer Society.
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- 2019
11. Rationale, design and baseline characteristics of the effect of ticagrelor on health outcomes in diabetes mellitus patients Intervention study
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Bhatt, Deepak L., Fox, Kim, Harrington, Robert A., Leiter, Lawrence A., Mehta, Shamir R., Simon, Tabassome, Andersson, Marielle, Himmelmann, Anders, Ridderstrale, Wilhelm, Held, Claes, Steg, Philippe Gabriel, Steg, Gabriel, Diaz, Rafael, Amerena, John, Huber, Kurt, Sinnaeve, Peter, Nicolau, Jose Carlos, Kerr Saraiva, Jose Francisco, Petrov, Ivo, Corbalan, Ramon, Ge, Junbo, Zhao, Qiang, Botero, Rodrigo, Widimsky, Petr, Kristensen, Steen Dalby, Hartikainen, Juha, Danchin, Nicolas, Darius, Harald, Fat, Tse Hung, Kiss, Robert Gabor, Pais, Prem, Lev, Eli, De Luca, Leonardo, Goto, Shinya, Ramos Lopez, Gabriel Arturo, Cornel, Jan Hein, Kontny, Frederic, Medina, Felix, Babilonia, Noe, Opolski, Grzegorz, Vinereanu, Dragos, Zateyshchikov, Dmitry, Ruda, Mikhail, Elamin, Omer, Kovar, Frantisek, Dalby, Anthony John, Jeong, Myung Ho, Bueno, Hector, James, Stefan, Chiang, Chern-En, Tresukosol, Damras, Ongen, Zeki, Ray, Kausik, Parkhomenko, Alexander, McGuire, Darren, Kosiborod, Mikhail, Nguyen, Tuan Quang, Wallentin, Lars, Fox, Keith A. A., Eikelboom, John W., Tuomilehto, Jaakko, Lee, Kerry L., Al-Khalidi, Hussein R., Ellis, Stephen J., Hagström, Emil, Holmgren, Pernilla, Heldestad, Ulrika, Hallberg, Theresa, Renlund Grausne, Karin, Alm, Cristina, Michelgård Palmquist, Åsa, Svanberg, Camilla, Capell, Warren H., Nehler, Mark R., Hiatt, William R., Bonaca, Marc P., Houser, Stacey, Bachler, Susie, Jaeger, Nicole, Aunes, Maria, Brusehed, Asa, Chen, Jersey, Dahlof, Bjorn, Dolezalova, Jitka, Domzol, Maciej, Findley, Magdalena, Holmberg, Niclas, Jahreskog, Marianne, Knutsson, Mikael, Kruszewski, Jakub, Leonsson-Zachrisson, Maria, Stark, Maj, Winder, Elin, and Sinnaeve, P
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Male ,Ticagrelor ,Cardiac & Cardiovascular Systems ,Time Factors ,medicine.medical_treatment ,Vascular damage Radboud Institute for Health Sciences [Radboudumc 16] ,Myocardial Infarction ,general clinical cardiology/adult ,Coronary Artery Disease ,Type 2 diabetes ,030204 cardiovascular system & hematology ,Stroke/mortality ,antiplatelet therapy ,Hypoglycemic Agents/adverse effects ,Coronary artery disease ,DOUBLE-BLIND ,0302 clinical medicine ,Risk Factors ,ARTERY-DISEASE ,Medicine ,Cardiac and Cardiovascular Systems ,030212 general & internal medicine ,Myocardial infarction ,1102 Cardiorespiratory Medicine and Haematology ,Stroke ,Randomized Controlled Trials as Topic ,Aspirin ,Kardiologi ,adult ,general clinical cardiology ,60 MG ,Ticagrelor/administration & dosage ,General Medicine ,Middle Aged ,Clopidogrel ,Treatment Outcome ,CLOPIDOGREL ,diabetes mellitus ,Cardiology ,PLATELET INHIBITION ,Drug Therapy, Combination ,Female ,Cardiology and Cardiovascular Medicine ,Life Sciences & Biomedicine ,medicine.drug ,medicine.medical_specialty ,Trial Designs ,03 medical and health sciences ,Diabetes Mellitus, Type 2/diagnosis ,Double-Blind Method ,Internal medicine ,Humans ,Hypoglycemic Agents ,CARDIOVASCULAR EVENTS ,Aspirin/administration & dosage ,Myocardial Infarction/mortality ,Platelet Aggregation Inhibitors/administration & dosage ,Aged ,clinical trials ,Science & Technology ,business.industry ,ACUTE CORONARY SYNDROMES ,Percutaneous coronary intervention ,medicine.disease ,ischemic heart disease ,ASPIRIN ,MYOCARDIAL-INFARCTION ,Cardiovascular System & Hematology ,Clinical Trials, Phase III as Topic ,Diabetes Mellitus, Type 2 ,Cardiovascular System & Cardiology ,Coronary Artery Disease/diagnosis ,business ,THEMIS Steering Committee ,Platelet Aggregation Inhibitors - Abstract
In the setting of prior myocardial infarction, the oral antiplatelet ticagrelor added to aspirin reduced the risk of recurrent ischemic events, especially, in those with diabetes mellitus. Patients with stable coronary disease and diabetes are also at elevated risk and might benefit from dual antiplatelet therapy. The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS, NCT01991795) is a Phase 3b randomized, double-blinded, placebo-controlled trial of ticagrelor vs placebo, on top of low dose aspirin. Patients ≥50 years with type 2 diabetes receiving anti-diabetic medications for at least 6 months with stable coronary artery disease as determined by a history of previous percutaneous coronary intervention, bypass grafting, or angiographic stenosis of ≥50% of at least one coronary artery were enrolled. Patients with known prior myocardial infarction (MI) or stroke were excluded. The primary efficacy endpoint is a composite of cardiovascular death, myocardial infarction, or stroke. The primary safety endpoint is Thrombolysis in Myocardial Infarction major bleeding. A total of 19 220 patients worldwide have been randomized and at least 1385 adjudicated primary efficacy endpoint events are expected to be available for analysis, with an expected average follow-up of 40 months (maximum 58 months). Most of the exposure is on a 60 mg twice daily dose, as the dose was lowered from 90 mg twice daily partway into the study. The results may revise the boundaries of efficacy for dual antiplatelet therapy and whether it has a role outside acute coronary syndromes, prior myocardial infarction, or percutaneous coronary intervention. ispartof: CLINICAL CARDIOLOGY vol:42 issue:5 pages:498-505 ispartof: location:United States status: published
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- 2019
12. Gender and age differences in outcomes of patients with acute coronary syndromes referred for coronary angiography
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Philipp Jakob, Roland Klingenberg, François Mach, Ulf Landmesser, Baris Gencer, Willibald Maier, Lorenz Räber, Stephan Windecker, Christian M. Matter, Barbara E. Stähli, Thomas F. Lüscher, David Nanchen, Dik Heg, Manfred Wischnewsky, Slayman Obeid, Peter Jüni, University of Zurich, and Maier, Willibald
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Coronary angiography ,Male ,Ticagrelor ,Purinergic P2Y Receptor Antagonists/administration & dosage ,health care facilities, manpower, and services ,030204 cardiovascular system & hematology ,Coronary Angiography ,Coronary artery disease ,0302 clinical medicine ,Risk Factors ,030212 general & internal medicine ,Myocardial infarction ,Prospective Studies ,Coronary Artery Bypass ,610 Medicine & health ,Stroke ,Referral and Consultation ,ddc:616 ,Aged, 80 and over ,Age Factors ,General Medicine ,Middle Aged ,humanities ,Clopidogrel ,Intention to Treat Analysis ,Treatment Outcome ,Cohort ,10209 Clinic for Cardiology ,Drug Therapy, Combination ,Female ,Cardiology and Cardiovascular Medicine ,TIMI ,Switzerland ,360 Social problems & social services ,Acute coronary syndrome ,medicine.medical_specialty ,Risk Assessment ,2705 Cardiology and Cardiovascular Medicine ,03 medical and health sciences ,Percutaneous Coronary Intervention ,Sex Factors ,Predictive Value of Tests ,Internal medicine ,medicine ,Humans ,2741 Radiology, Nuclear Medicine and Imaging ,Radiology, Nuclear Medicine and imaging ,Acute Coronary Syndrome ,Healthcare Disparities ,Aspirin/administration & dosage ,Platelet Aggregation Inhibitors/administration & dosage ,Adenosine/administration & dosage/analogs & derivatives ,Aged ,Coronary Artery Disease/drug therapy/mortality ,business.industry ,Drug-Eluting Stents/adverse effects ,social sciences ,medicine.disease ,Institutional repository ,Ticlopidine/administration & dosage/analogs & derivatives ,business ,Myocardial Infarction/mortality/prevention & control - Abstract
OBJECTIVES The number of elderly patients undergoing coronary revascularization is steadily increasing, and data on the impact of gender on outcomes are scarce. This study sought to assess gender-related differences in outcomes in elderly patients with acute coronary syndromes (ACS). METHODS We investigated outcomes in elderly ACS patients referred for coronary angiography and prospectively enrolled in the Swiss ACS Cohort between December 2009 and October 2012. Adjudicated major adverse cardiovascular and cerebrovascular events (MACCE) included all-cause death, non-fatal myocardial infarction, clinically indicated repeat coronary revascularization, definite stent thrombosis, and transient ischemic attack/stroke. RESULTS Among 2,168 patients recruited, 481 (22%) patients were >75 years of age (37% women). In patients >75 years, 1-year MACCE rates were 15% and 23% in women and men (OR 0.59, 95% CI 0.36-0.97, P = 0.04), respectively, and differences remained significant after adjustments for baseline variables (adjusted OR 0.48, 95% CI 0.26-0.90, P = 0.02). Women >75 years had a lower cardiovascular mortality (6% versus 12%, adjusted OR 0.31, 95% CI 0.12-0.81, P = 0.02). In patients ≤75 years, 1-year MACCE rates did not differ between gender (10% and 8% for women and men, adjusted OR 1.28, 95% CI 0.77-2.14, P = 0.34). Rates of TIMI major bleeding for women and men were 4% and 4% in patients >75 years (P = 0.96), and 5% and 3% in those ≤75 years (P = 0.11). CONCLUSIONS The low rates of MACCE observed in elderly women in this patient cohort suggest that with current interventional strategies the gender gap in ACS management has been attenuated.
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- 2019
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13. Rivaroxaban with or without aspirin in patients with stable coronary artery disease : an international, randomised, double-blind, placebo-controlled trial
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Stuart J Connolly, John W Eikelboom, Jackie Bosch, Gilles Dagenais, Leanne Dyal, Fernando Lanas, Kaj Metsarinne, Martin O'Donnell, Anthony L Dans, Jong-Won Ha, Alexandr N Parkhomenko, Alvaro A Avezum, Eva Lonn, Liu Lisheng, Christian Torp-Pedersen, Petr Widimsky, Aldo P Maggioni, Camilo Felix, Katalin Keltai, Masatsugu Hori, Khalid Yusoff, Tomasz J Guzik, Deepak L Bhatt, Kelley R H Branch, Nancy Cook Bruns, Scott D Berkowitz, Sonia S Anand, John D Varigos, Keith A A Fox, 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, and OVIDIU CHIONCEL
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Male ,medicine.medical_treatment ,Myocardial Infarction ,Coronary Artery Disease ,030204 cardiovascular system & hematology ,Stroke/epidemiology ,Coronary artery disease ,0302 clinical medicine ,Rivaroxaban ,Hemorrhage/chemically induced ,Carotid artery disease ,030212 general & internal medicine ,Myocardial infarction ,Cardiovascular Diseases/mortality ,Aspirin ,Atrial fibrillation ,General Medicine ,Stroke ,ORAL RIVAROXABAN ,Cardiovascular Diseases ,Factor Xa Inhibitors/administration & dosage ,Cardiology ,Female ,Drug Therapy, Combination ,medicine.drug ,medicine.medical_specialty ,Rivaroxaban/administration & dosage ,Coronary Artery Disease/drug therapy ,Hemorrhage ,Drug Administration Schedule ,03 medical and health sciences ,Double-Blind Method ,Internal medicine ,Journal Article ,Myocardial Infarction/epidemiology ,medicine ,Humans ,Aspirin/administration & dosage ,Platelet Aggregation Inhibitors/administration & dosage ,Aged ,Dose-Response Relationship, Drug ,business.industry ,Unstable angina ,Percutaneous coronary intervention ,medicine.disease ,PREVENTION ,Morbidity ,business ,Platelet Aggregation Inhibitors ,Factor Xa Inhibitors - Abstract
BACKGROUND: Coronary artery disease is a major cause of morbidity and mortality worldwide, and is a consequence of acute thrombotic events involving activation of platelets and coagulation proteins. Factor Xa inhibitors and aspirin each reduce thrombotic events but have not yet been tested in combination or against each other in patients with stable coronary artery disease.METHODS: In this multicentre, double-blind, randomised, placebo-controlled, outpatient trial, patients with stable coronary artery disease or peripheral artery disease were recruited at 602 hospitals, clinics, or community centres in 33 countries. This paper reports on patients with coronary artery disease. Eligible patients with coronary artery disease had to have had a myocardial infarction in the past 20 years, multi-vessel coronary artery disease, history of stable or unstable angina, previous multi-vessel percutaneous coronary intervention, or previous multi-vessel coronary artery bypass graft surgery. After a 30-day run in period, patients were randomly assigned (1:1:1) to receive rivaroxaban (2·5 mg orally twice a day) plus aspirin (100 mg once a day), rivaroxaban alone (5 mg orally twice a day), or aspirin alone (100 mg orally once a day). Randomisation was computer generated. Each treatment group was double dummy, and the patients, investigators, and central study staff were masked to treatment allocation. The primary outcome of the COMPASS trial was the occurrence of myocardial infarction, stroke, or cardiovascular death. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants.FINDINGS: Between March 12, 2013, and May 10, 2016, 27 395 patients were enrolled to the COMPASS trial, of whom 24 824 patients had stable coronary artery disease from 558 centres. The combination of rivaroxaban plus aspirin reduced the primary outcome more than aspirin alone (347 [4%] of 8313 vs 460 [6%] of 8261; hazard ratio [HR] 0·74, 95% CI 0·65-0·86, pINTERPRETATION: In patients with stable coronary artery disease, addition of rivaroxaban to aspirin lowered major vascular events, but increased major bleeding. There was no significant increase in intracranial bleeding or other critical organ bleeding. There was also a significant net benefit in favour of rivaroxaban plus aspirin and deaths were reduced by 23%. Thus, addition of rivaroxaban to aspirin has the potential to substantially reduce morbidity and mortality from coronary artery disease worldwide.FUNDING: Bayer AG.
- Published
- 2018
14. Rivaroxaban or Aspirin for Extended Treatment of Venous Thromboembolism
- Author
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Weitz, Jeffrey I., Lensing, Anthonie W.A., Prins, Martin H., Bauersachs, Rupert, Beyer-Westendorf, Jan, Bounameaux, Henri, Brighton, Timothy A., Cohen, Alexander T., Davidson, Bruce L., Decousus, Hervé, Freitas, Maria C.S., Holberg, Gerlind, Kakkar, Ajay K., Haskell, Lloyd, Van Bellen, Bonno, Pap, Akos F., Berkowitz, Scott D., Verhamme, Peter, Wells, Philip S., Prandoni, Paolo, Riera Mestre, Antoni, EINSTEIN CHOICE Investigators, McMaster University [Hamilton, Ontario], Klinikum Darmstadt (RMB), Klinikum Darmstadt, Carl Gustav Carus University (DRESDEN - CGCU), Technische Universität Dresden = Dresden University of Technology (TU Dresden), Service d'angiologie et d'hémostase (MR), Hôpital Universitaire de Genève, King's College Hospital (KCH), Groupe de recherche sur la thrombose (GRT (EA 3065)), Université Jean Monnet [Saint-Étienne] (UJM), University of Ottawa [Ottawa], Thromboembolism Unit (PP), Universita degli Studi di Padova, 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), CIC Brest, Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Cavale Blanche, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, ACS - Pulmonary hypertension & thrombosis, MUMC+: KIO Kemta (9), RS: CAPHRI - R5 - Optimising Patient Care, Epidemiologie, Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), EINSTEIN CHOICE Investigators, Bianchi, A., Brighton, T., Carroll, P., Chong, B., Chunilal, S., Coughlin, P., Curnow, J., Jackson, D., Tran, H., Ward, C., Brodmann, M., Kyrle, P., Marschang, P., Petkov, V., Hainaut, P., Jordens, P., Vandekerkhof, J., Verhamme, P., Wautrecht, J-C, Annichino-Bizzacchi, J., van Bellen, B., Correa, J., Cukier, A., Freire, A., Pereira, A., Porto, C., Sacilotto, R., Vasconcelos Costa, A., Della Siega, A., Dolan, S., Le Gal, G., Gross, P., Kahn, S., Kassis, J., Kovacs, M., Pesant, Y., Ritchie, B., Schulman, S., Shivakumar, S., Solymoss, S., Chang, S., Chen, R., Chen, Z., Chen, H., Dai, X., Fang, B., Fu, W., Gao, X., Huang, J., Lai, Y., Li, L., Li, X., Li, Y., Liu, J., Liu, S., Ma, W., Ni, S., Qin, Z., Shi, G., Tian, H., Wang, S., Wang, L., Xiao, W., Ying, K., Yu, G., Yuan, Y., Zhang, J., Zhang, X., Zhang, L., Zhu, L., Chlumský, J., Chochola, J., Dunaj, M., Kovarova, K., Lang, P., Matoška, P., Podpera, I., Spacek, R., Stehlikova, O., Brønnum-Schou, J., Egstrup, K., Gislason, G., Jeppesen, J., May, O., Nielsen, H., Wiggers, H., Achkar, A., Aquilanti, S., Benhamou, Y., Brisot, D., Bura-Riviere, A., Castella, N., Elias, A., Falvo, N., Ferrari, E., Lacroix, P., Mahe, I., Meneveau, N., Messas, E., Mismetti, P., Montaclair, K., Mottier, D., Moumneh, T., Paleiron, N., Parent, F., Pernod, G., Sanchez, O., Schmidt, J., Simoneau, G., Stephan, D., Amann, B., Bauersachs, R., Beyer-Westendorf, J., Blessing, E., Czihal, M., Espinola-Klein, C., Kahrmann, G., Licka, M., Neumeister, A., Schellong, S., Boda, Z., Farkas, K., Gurzo, M., Katona, A., Riba, M., Sipos, G., Tóth, K., Braester, A., Elias, M., Gafter-Gvili, A., Gavish, D., Hussein, O., Lishner, M., Schiff, E., Spectre, G., Tzoran-Rozenthal, I., Zimlichman, R., Ageno, W., Agnelli, G., Bova, C., Garbelotto, R., Ghirarduzzi, A., Imberti, D., Pesavento, R., Porreca, E., Visonà, A., Flota Cervera, L., Llamas Esperón, G., Rodriguez-Gonzalez, D., Solis Morales, L., Boersma, W., ten Cate, H., Erdkamp, F., Grifioen-Keijzer, A., Marwijk Kooy, M., Meijer, K., Middeldorp, S., Swart-Heikens, J., Ten Wolde, M., Westerweel, P., Braithwaite, I., Harper, P., Merriman, E., Ockelford, P., Royle, G., Smith, M., Ghanima, W., Sandset, P.M., Abola, M., Chęciński, P., Grzelakowski, P., Lewczuk, J., Sobkowicz, B., Tomkowski, W., Abramov, I., Chechulov, P., Karpenko, A., Katelnitskiy, I., Kazakov, A., Makarova, O., Panchenko, E., Sergeeva, E., Subbotin, Y., Suchkov, I., Zeltser, M., Adler, D., Breedt, J., Fourie, N., Isaacs, R., Jacobson, B., Siebert, H., van Zyl, L., Choi, J-H, Kang, S-M, Kim, K-H, Kim, H-S, Kim, D-I, Min, S-K, Park, K.H., García-Bragado Dalmau, F., Gómez Cerezo, J., Mirete, JCF, Riera, A., Del Toro, J., Eriksson, H., Torstensson, I., Banyai, M., Baumgartner, I., Mazzolai, L., Periard, D., Righini, M., Staub, D., Chiang, C-E, Chiu, K-M, Pai, P-Y, Angchaisuksiri, P., Chansung, K., Öngen, G., Tuncay, E., Alikhan, R., Chetter, I., Kesteven, P., Nokes, T., Bauer, K., Comerota, A., Elias, D., Garcia, D., Gibson, K., Ginsberg, D., Jenkins, J., Kingsley, E., Lambert, R., Lyons, R., Pullman, J., Shah, V., Smith, S.W., Stein, R., Tapson, V., Walsh, J., Wang, T-F, Do Loi, D., Do Quang, H., and Pham, N.
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Male ,[SDV]Life Sciences [q-bio] ,Phases of clinical research ,Kaplan-Meier Estimate ,030204 cardiovascular system & hematology ,Factor Xa Inhibitors/administration & dosage/adverse effects ,law.invention ,TOTAL KNEE ARTHROPLASTY ,0302 clinical medicine ,Randomized controlled trial ,Rivaroxaban ,ENOXAPARIN ,law ,Hemorrhage/chemically induced ,Secondary Prevention ,NONSURGICAL PATIENTS ,030212 general & internal medicine ,THROMBOPROPHYLAXIS ,ComputingMilieux_MISCELLANEOUS ,ddc:616 ,Aspirin ,Atrial fibrillation ,General Medicine ,Venous Thromboembolism ,Middle Aged ,Thrombosis ,Intention to Treat Analysis ,Anesthesia ,Adult ,Aged ,Aspirin/administration & dosage ,Aspirin/adverse effects ,Double-Blind Method ,Drug Administration Schedule ,Factor Xa Inhibitors/administration & dosage ,Factor Xa Inhibitors/adverse effects ,Female ,Humans ,Platelet Aggregation Inhibitors/administration & dosage ,Platelet Aggregation Inhibitors/adverse effects ,Rivaroxaban/administration & dosage ,Rivaroxaban/adverse effects ,Venous Thromboembolism/mortality ,Venous Thromboembolism/prevention & control ,medicine.drug ,medicine.medical_specialty ,LONG-TERM ,Platelet Aggregation Inhibitors/administration & dosage/adverse effects ,Venous Thromboembolism/mortality/prevention & control ,INTENSITY WARFARIN THERAPY ,Hemorrhage ,HIP-ARTHROPLASTY ,03 medical and health sciences ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,Thromboembolism ,medicine ,Mortalitat ,Aspirina ,Mortality ,Tromboembolisme ,Intention-to-treat analysis ,business.industry ,medicine.disease ,PREVENTION ,Surgery ,Aspirin/administration & dosage/adverse effects ,Clinical trial ,THROMBOSIS ,ATRIAL-FIBRILLATION ,Rivaroxaban/administration & dosage/adverse effects ,business ,Platelet Aggregation Inhibitors ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,Factor Xa Inhibitors - Abstract
Background: although many patients with venous thromboembolism require extended treatment, it is uncertain whether it is better to use full- or lower-intensity anticoagulation therapy or aspirin. Methods: in this randomized, double-blind, phase 3 study, we assigned 3396 patients with venous thromboembolism to receive either once-daily rivaroxaban (at doses of 20 mg or 10 mg) or 100 mg of aspirin. All the study patients had completed 6 to 12 months of anticoagulation therapy and were in equipoise regarding the need for continued anticoagulation. Study drugs were administered for up to 12 months. The primary efficacy outcome was symptomatic recurrent fatal or nonfatal venous thromboembolism, and the principal safety outcome was major bleeding. Results: a total of 3365 patients were included in the intention-to-treat analyses (median treatment duration, 351 days). The primary efficacy outcome occurred in 17 of 1107 patients (1.5%) receiving 20 mg of rivaroxaban and in 13 of 1127 patients (1.2%) receiving 10 mg of rivaroxaban, as compared with 50 of 1131 patients (4.4%) receiving aspirin (hazard ratio for 20 mg of rivaroxaban vs. aspirin, 0.34; 95% confidence interval [CI], 0.20 to 0.59; hazard ratio for 10 mg of rivaroxaban vs. aspirin, 0.26; 95% CI, 0.14 to 0.47; P
- Published
- 2017
15. Clopidogrel paclitaxel drug-drug interaction:A pharmacoepidemiologic study
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Tore Bjerregaard Stage, Kim Brøsen, K. Agergaard, Karina Dahl Steffensen, Troels K Bergmann, R.E. Hassel, M.L.H. Milo, J.W. Pedersen, Jesper Hallas, Trine Lembrecht Jørgensen, Morten Mau-Sørensen, S.H. Poulsen, and Anton Pottegård
- Subjects
Male ,Pharmacology ,Ticlopidine/administration & dosage ,030226 pharmacology & pharmacy ,Gastroenterology ,Severity of Illness Index ,chemistry.chemical_compound ,0302 clinical medicine ,Pharmacology (medical) ,Drug Interactions ,Aspirin ,Cumulative dose ,Hazard ratio ,Peripheral Nervous System Diseases ,Middle Aged ,Clopidogrel ,Liver ,Paclitaxel ,030220 oncology & carcinogenesis ,Female ,medicine.drug ,Liver/metabolism ,medicine.medical_specialty ,Cytochrome P-450 CYP2C8/metabolism ,Ticlopidine ,Peripheral Nervous System Diseases/chemically induced ,Cytochrome P-450 CYP2C8 ,03 medical and health sciences ,Internal medicine ,Paclitaxel/administration & dosage ,medicine ,Journal Article ,Humans ,Aspirin/administration & dosage ,Platelet Aggregation Inhibitors/administration & dosage ,Aged ,Retrospective Studies ,Dose-Response Relationship, Drug ,business.industry ,Pharmacoepidemiology ,Retrospective cohort study ,Confidence interval ,Regimen ,chemistry ,business ,Platelet Aggregation Inhibitors - Abstract
Paclitaxel is mainly eliminated by CYP2C8 in the liver. CYP2C8 is strongly inhibited by the clopidogrel metabolite acyl-β-D-glucuronide. To determine if this interaction has clinical relevance, we identified 48 patients treated with clopidogrel and paclitaxel using databases and a prescription register. Peripheral sensory neuropathy was retrospectively evaluated from medical charts and compared to that of 88 age and sex matched controls treated with paclitaxel and low dose aspirin. By a cumulative dose of 1500 mg paclitaxel, 35% of the patients had developed severe neuropathy. The overall hazard ratio between clopidogrel use and severe paclitaxel neuropathy was 1.7 (95% CI, 0.9-3.0). Among those receiving a high dose paclitaxel regimen, the hazard ratio was 2.3 (95% CI, 1.1-4.5). Our study indicates that clopidogrel is associated with a clinically relevant increased risk of neuropathy in patients treated with high dose paclitaxel. This article is protected by copyright. All rights reserved.
- Published
- 2017
16. Safety of Proton Pump Inhibitors Based on a Large, Multi-Year, Randomized Trial of Patients Receiving Rivaroxaban or Aspirin
- Author
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Sonia S. Anand, Paul Moayyedi, Eva Muehlhofer, Leanne Dyal, Stuart J. Connolly, P. Gabriel Steg, Robert G. Hart, Salim Yusuf, Alvaro Avezum, Camilo Felix, Marco Alings, Patrick J. Commerford, Peter Verhamme, Tomek J. Guzik, Dragos Vinereanu, Patricio Lopez-Jaramillo, Georg Ertl, Petr Widimsky, Eva Lonn, Olga Shestakovska, John W. Eikelboom, Martin O'Donnell, Masatsugu Hori, Yan Liang, Andrew Tonkin, Aldo P. Maggioni, Leopoldo S. Piegas, Deepak L. Bhatt, Jae-Hyung Kim, Kelley R. Branch, Jackie Bosch, Keith A.A. Fox, Jun Zhu, Fernando Lanas, Kaj Metsärinne, Lars Rydén, Alexander Parkhomenko, Rafael Diaz, Antonio L. Dans, Matyas Keltai, Basil S. Lewis, Nana Pogosova, Christian Torp-Pedersen, Ajay K. Kakkar, Jeffrey L. Probstfield, Gilles R. Dagenais, Khalid Yusoff, Stefan Störk, Darryl P. Leong, and Nancy Cook Bruns
- Subjects
Male ,0301 basic medicine ,Time Factors ,law.invention ,0302 clinical medicine ,Rivaroxaban ,Randomized controlled trial ,Risk Factors ,law ,Medicine ,Prospective Studies ,Pantoprazole ,Enterocolitis, Pseudomembranous ,Cardiovascular Diseases/diagnosis ,Aspirin ,Enterocolitis, Pseudomembranous/chemically induced ,Gastroenterology ,Middle Aged ,Obstructive lung disease ,Pantoprazole/administration & dosage ,Proton Pump Inhibitors/administration & dosage ,Treatment Outcome ,Peripheral Arterial Disease/diagnosis ,Cardiovascular Diseases ,Factor Xa Inhibitors/administration & dosage ,Female ,030211 gastroenterology & hepatology ,Gastrointestinal Hemorrhage ,medicine.drug ,medicine.medical_specialty ,medicine.drug_class ,Rivaroxaban/administration & dosage ,Proton-pump inhibitor ,Placebo ,Risk Assessment ,Drug Administration Schedule ,Peripheral Arterial Disease ,03 medical and health sciences ,Double-Blind Method ,Internal medicine ,Humans ,Aspirin/administration & dosage ,Adverse effect ,Platelet Aggregation Inhibitors/administration & dosage ,Aged ,Hepatology ,business.industry ,Proton Pump Inhibitors ,medicine.disease ,030104 developmental biology ,business ,Platelet Aggregation Inhibitors ,Gastrointestinal Hemorrhage/chemically induced ,Factor Xa Inhibitors ,Kidney disease - Abstract
BACKGROUND & AIMS: Proton pump inhibitors (PPIs) are effective at treating acid-related disorders. These drugs are well tolerated in the short term, but long-term treatment was associated with adverse events in observational studies. We aimed to confirm these findings in an adequately powered randomized trial.METHODS: We performed a 3 × 2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease randomly assigned to groups given pantoprazole (40 mg daily, n = 8791) or placebo (n = 8807). Participants were also randomly assigned to groups that received rivaroxaban (2.5 mg twice daily) with aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg) alone. We collected data on development of pneumonia, Clostridium difficile infection, other enteric infections, fractures, gastric atrophy, chronic kidney disease, diabetes, chronic obstructive lung disease, dementia, cardiovascular disease, cancer, hospitalizations, and all-cause mortality every 6 months. Patients were followed up for a median of 3.01 years, with 53,152 patient-years of follow-up.RESULTS: There was no statistically significant difference between the pantoprazole and placebo groups in safety events except for enteric infections (1.4% vs 1.0% in the placebo group; odds ratio, 1.33; 95% confidence interval, 1.01-1.75). For all other safety outcomes, proportions were similar between groups except for C difficile infection, which was approximately twice as common in the pantoprazole vs the placebo group, although there were only 13 events, so this difference was not statistically significant.CONCLUSIONS: In a large placebo-controlled randomized trial, we found that pantoprazole is not associated with any adverse event when used for 3 years, with the possible exception of an increased risk of enteric infections. ClinicalTrials.gov Number: NCT01776424.
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- 2019
17. Optimizing the Use of Aspirin for Cardiovascular Prevention
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Carlos Sostres, Ruben Casado-Arroyo, Angel Lanas, and Faculty of Medicine and Pharmacy
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Gastrointestinal bleeding ,medicine.medical_specialty ,Acute coronary syndrome ,Anti-Inflammatory Agents, Non-Steroidal/administration & dosage ,Pharmacology ,Pharmacotherapy ,Cardiovascular prevention ,Risk Factors ,Gastrointestinal Hemorrhage/prevention & control ,medicine ,Humans ,Pharmacology (medical) ,Aspirin/administration & dosage ,Intensive care medicine ,Platelet Aggregation Inhibitors/administration & dosage ,Aspirin ,Dose-Response Relationship, Drug ,business.industry ,Anti-Inflammatory Agents, Non-Steroidal ,medicine.disease ,Clopidogrel ,Cardiovascular Diseases ,Pharmacodynamics ,Concomitant ,Practice Guidelines as Topic ,Cardiovascular Diseases/drug therapy ,Gastrointestinal Hemorrhage ,business ,Platelet Aggregation Inhibitors ,medicine.drug - Abstract
This article describes the mechanism of action, pharmacokinetics, and pharmacodynamics of aspirin at doses used for cardiovascular prevention and provides specific management recommendations for optimal use in clinical practice. The paper highlights practical aspects related to antiplatelet therapy, including the optimal dose of aspirin, concomitant treatment with other NSAIDs, and strategies for the prevention of gastrointestinal toxicity. Specifically, we revise the benefits and hazards in different clinical settings to help the clinician in the decision-making process for individuals who have different risks for cardiovascular and gastrointestinal bleeding events.
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- 2013
18. Use of low-dose aspirin and non-aspirin nonsteroidal anti-inflammatory drugs and risk of glioma: a case–control study
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Luis A. García-Rodríguez, Søren Friis, Jesper Hallas, David Gaist, and Henrik Toft Sørensen
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Male ,Cancer Research ,Time Factors ,Epidemiology ,Anti-Inflammatory Agents, Non-Steroidal/administration & dosage ,Denmark ,Gastroenterology ,chemistry.chemical_compound ,Risk Factors ,glioma ,Brain Neoplasms/epidemiology ,Young adult ,skin and connective tissue diseases ,risk ,Aged, 80 and over ,Aspirin ,Brain Neoplasms ,Anti-Inflammatory Agents, Non-Steroidal ,Glioma ,Middle Aged ,non-aspirin NSAIDs ,Oncology ,epidemiology ,Female ,medicine.drug ,musculoskeletal diseases ,Adult ,medicine.medical_specialty ,aspirin ,Glioma/epidemiology ,medicine.drug_class ,digestive system ,Anti-inflammatory ,Young Adult ,Internal medicine ,medicine ,Humans ,Aspirin/administration & dosage ,Aged ,Nonsteroidal ,business.industry ,Case-control study ,medicine.disease ,digestive system diseases ,Denmark/epidemiology ,nervous system diseases ,chemistry ,Case-Control Studies ,Immunology ,business ,Low dose aspirin - Abstract
Background: Few studies have examined the association between use of aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) and risk of glioma and the results have been equivocal. We therefore investigated the influence of NSAID use on glioma risk in a nationwide setting. Methods: We used national registries in Denmark to identify all patients aged 20-85 years with a first diagnosis of histologically verified glioma during 2000-2009. Each case was matched on birth year and sex to eight population controls using risk-set sampling. We used prescription data to assess NSAID use and classified exposure to low-dose aspirin or non-aspirin (NA) NSAIDs into ever use or long-term use, defined as continuous use for ≥5 years. Conditional logistic regression was used to compute odds ratios (ORs), with 95% confidence intervals (CIs), for glioma associated with NSAID use, adjusted for potential confounders.Results:A total of 2688 glioma cases and 18 848 population controls were included in the study. Ever use of low-dose aspirin (OR=0.90; 95% CI: 0.77-1.04) or NA-NSAIDs (OR=1.05; 95% CI: 0.96-1.14) was not associated with glioma risk. Compared with never use, long-term use of low-dose aspirin or of NA-NSAIDs was associated with ORs of 0.80 (95% CI: 0.53-1.21) and 1.11 (0.57-2.17), respectively. We observed no clear patterns of risk in stratified analysis according to estimated doses of low-dose aspirin (≤100 mg, 150 mg). Conclusion: We did not find any apparent association between aspirin or NA-NSAID use and risk of glioma, although our results may be consistent with a slight reduction in glioma risk with long-term use of low-dose aspirin.
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- 2013
19. Enteric coating can lead to reduced antiplatelet effect of low-dose acetylsalicylic acid
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Dorte Ejg Jarbøl, Peter Haastrup, and Thor Grønlykke
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Blood Platelets ,Platelet Aggregation ,Biological Availability ,Pharmacology ,Bioequivalence ,Toxicology ,Pharmacokinetics ,Antithrombotic ,medicine ,Humans ,Lead (electronics) ,Aspirin/administration & dosage ,Platelet Aggregation Inhibitors/administration & dosage ,Platelet Aggregation/drug effects ,Clinical Trials as Topic ,Aspirin ,business.industry ,Low dose ,General Medicine ,Enteric coating ,digestive system diseases ,Bioavailability ,surgical procedures, operative ,Blood Platelets/drug effects ,Tablets, Enteric-Coated ,business ,Platelet Aggregation Inhibitors ,Biological availability ,medicine.drug - Abstract
Low-dose acetylsalicylic acid (ASA) is widely used as antithrombotic prophylaxis. Enteric coated ASA has been developed in order to decrease the risk of gastrointestinal side effects. The consequences of enteric coating on pharmacokinetics and antiplatelet effect of ASA have not systematically been assessed. This MiniReview demonstrates that data from clinical trials indicate that enteric coating can reduce the antiplatelet effect of ASA compared to plain ASA. This is possibly due to decreased bioavailability of ASA caused by prolonged solvation and absorption of the enteric coated formulations. Therefore, low dose enteric coated ASA might not be bioequivalent to plain ASA, entailing the risk of insufficient cardiovascular prophylaxis.
- Published
- 2015
20. Remote ischaemic conditioning before hospital admission, as a complement to angioplasty, and effect on myocardial salvage in patients with acute myocardial infarction: a randomised trial
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Andrew N. Redington, Hans Erik Bøtker, Morten Bøttcher, Niels Holmark Andersen, Steen Dalby Kristensen, Sven Trautner, Søren Steen Nielsen, Torsten Toftegaard Nielsen, Christian Juhl Terkelsen, Jens Flensted Lassen, Leif Thuesen, Rajesh K. Kharbanda, Troels Martin Hansen, Michael Schmidt, Anne Kaltoft, Evald Høj Christiansen, Michael Rehling, Lars Romer Krusell, Henrik Toft Sørensen, and Kim Munk
- Subjects
Myocardium/pathology ,Male ,Time Factors ,medicine.medical_treatment ,Abciximab ,Myocardial Infarction ,Ticlopidine/administration & dosage ,Immunoglobulin Fab Fragments/administration & dosage ,Myocardial Infarction/therapy ,Electrocardiography ,Clinical endpoint ,Myocardial infarction ,Prospective Studies ,Angioplasty, Balloon, Coronary ,Troponin T/blood ,Arm/blood supply ,medicine.diagnostic_test ,Antibodies, Monoclonal ,General Medicine ,Middle Aged ,Clopidogrel ,Hospitalization ,Treatment Outcome ,Echocardiography ,Ischemic Preconditioning, Myocardial ,Cardiology ,Arm ,Drug Therapy, Combination ,Female ,Ischemic Preconditioning, Myocardial/methods ,Technetium Tc 99m Sestamibi ,medicine.medical_specialty ,Angioplasty, Balloon, Laser-Assisted ,Randomization ,Ticlopidine ,Myocardial Reperfusion Injury/prevention & control ,Myocardial Reperfusion Injury ,Antibodies, Monoclonal/administration & dosage ,Myocardial perfusion imaging ,Immunoglobulin Fab Fragments ,Troponin T ,Angioplasty ,Internal medicine ,medicine ,Humans ,Elective surgery ,Aspirin/administration & dosage ,Platelet Aggregation Inhibitors/administration & dosage ,Tomography, Emission-Computed, Single-Photon ,Aspirin ,business.industry ,Myocardium ,Percutaneous coronary intervention ,medicine.disease ,Surgery ,Heart failure ,Radiopharmaceuticals ,business ,Platelet Aggregation Inhibitors - Abstract
BACKGROUND: Remote ischaemic preconditioning attenuates cardiac injury at elective surgery and angioplasty. We tested the hypothesis that remote ischaemic conditioning during evolving ST-elevation myocardial infarction, and done before primary percutaneous coronary intervention, increases myocardial salvage.METHODS: 333 consecutive adult patients with a suspected first acute myocardial infarction were randomly assigned in a 1:1 ratio by computerised block randomisation to receive primary percutaneous coronary intervention with (n=166 patients) versus without (n=167) remote conditioning (intermittent arm ischaemia through four cycles of 5-min inflation and 5-min deflation of a blood-pressure cuff). Allocation was concealed with opaque sealed envelopes. Patients received remote conditioning during transport to hospital, and primary percutaneous coronary intervention in hospital. The primary endpoint was myocardial salvage index at 30 days after primary percutaneous coronary intervention, measured by myocardial perfusion imaging as the proportion of the area at risk salvaged by treatment; analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00435266.FINDINGS: 82 patients were excluded on arrival at hospital because they did not meet inclusion criteria, 32 were lost to follow-up, and 77 did not complete the follow-up with data for salvage index. Median salvage index was 0.75 (IQR 0.50-0.93, n=73) in the remote conditioning group versus 0.55 (0.35-0.88, n=69) in the control group, with median difference of 0.10 (95% CI 0.01-0.22; p=0.0333); mean salvage index was 0.69 (SD 0.27) versus 0.57 (0.26), with mean difference of 0.12 (95% CI 0.01-0.21; p=0.0333). Major adverse coronary events were death (n=3 per group), reinfarction (n=1 per group), and heart failure (n=3 per group).INTERPRETATION: Remote ischaemic conditioning before hospital admission increases myocardial salvage, and has a favourable safety profile. Our findings merit a larger trial to establish the effect of remote conditioning on clinical outcomes.FUNDING: Fondation Leducq.
- Published
- 2010
21. Aspirin plus ticlopidine prevented experimental endocarditis due toEnterococcus faecalisandStreptococcus gallolyticus
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Stefano Mancini, Tiago Rafael Veloso, José M. Entenza, Philippe Moreillon, Frank Oechslin, and Yok-Ai Que
- Subjects
Microbiology (medical) ,Ticlopidine ,Animals ,Aspirin/administration & dosage ,Disease Models, Animal ,Endocarditis, Bacterial/microbiology ,Endocarditis, Bacterial/prevention & control ,Enterococcus faecalis/growth & development ,Female ,Gram-Positive Bacterial Infections/microbiology ,Gram-Positive Bacterial Infections/prevention & control ,Platelet Aggregation Inhibitors/pharmacology ,Rats, Wistar ,Streptococcus/growth & development ,Ticlopidine/administration & dosage ,Treatment Outcome ,Short Communication ,Context (language use) ,medicine.disease_cause ,Enterococcus faecalis ,Microbiology ,medicine ,Immunology and Allergy ,Endocarditis ,Streptococcus gallolyticus ,Gram-Positive Bacterial Infections ,Aspirin ,General Immunology and Microbiology ,biology ,Streptococcus ,Endocarditis, Bacterial ,General Medicine ,medicine.disease ,biology.organism_classification ,Infectious Diseases ,Infective endocarditis ,Platelet aggregation inhibitor ,Platelet Aggregation Inhibitors ,medicine.drug - Abstract
Enterococcus faecalis and Streptococcus gallolyticus cause infective endocarditis (IE), which can originate from the continuous release or translocation of low bacterial numbers into the bloodstream. In this context, IE cannot be prevented with antibiotics. We previously demonstrated that aspirin plus ticlopidine protected rats from IE due to S. gordonii and Staphylococcus aureus. Here we showed that aspirin plus ticlopidine significantly reduced vegetation weight and protected 73 and 64% rats (P < 0.005) from IE due to E. faecalis and S. gallolyticus, respectively. These results further support the potential use of aspirin plus ticlopidine for a global prevention of IE in high-risk patients.
- Published
- 2015
22. Efficacy of tenecteplase in combination with enoxaparin, abciximab, or unfractionated heparin : one-year follow-up results of the Assessment of the Safety of a New Thrombolytic-3 (ASSENT-3) randomized trial in acute myocardial infarction.
- Published
- 2004
23. Low molecular weight heparin (dalteparin) compared to unfractionated heparin as an adjunct to rt-PA (alteplase) for improvement of coronary artery patency in acute myocardial infarction-the ASSENT Plus study.
- Published
- 2003
24. Low molecular weight heparin (dalteparin) compared to unfractionated heparin as an adjunct to rt-PA (alteplase) for improvement of coronary artery patency in acute myocardial infarction-the ASSENT Plus study.
- Published
- 2003
25. Kawasaki disease and aspirin
- Author
-
DavidW. Denning
- Subjects
Adult ,Aspirin ,medicine.medical_specialty ,Lymphatic Diseases/drug therapy ,business.industry ,General Medicine ,Mucocutaneous Lymph Node Syndrome ,medicine.disease ,Text mining ,Internal medicine ,Mucocutaneous Lymph Node Syndrome/drug therapy ,Medicine ,Humans ,Kawasaki disease ,Aspirin/administration & dosage ,business ,Child ,Lymphatic Diseases ,medicine.drug - Abstract
The use of high-dose aspirin therapy for Kawasaki disease,recommended by Dr Goel and his colleagues (June 25, p 144),requires comment. In the acute phase of the disease, high-doseaspirin is appropriate in an effort to ameliorate the acuteinflammatory response and reduce fever. The dose recommended,30 mg/kg/day, may be suitable, although this dose was no-better thana cephalosporin antibiotic in preventing the development ofcoronary-artery aneurysms. In the convalescent phase of theillness, when the incidence of sudden death is approximately 2%,the primary aim is to prevent death. Low-dose aspirin is likely tohave a role in preventing coronary-artery occlusion during thisphase.It is suggested that the reason why the dosage of aspirin is socritical in haemostasis is that it inhibits cyclo-oxygenase, which ispresent in both platelets and vessel walls. In the platelets theproducts of cyclo-oxygenase action include thromboxane A2 andmalondialdehyde, both of which aggregate platelets. In the vesselwall the same enzyme produces prostacyclin, which inhibits plateletaggregation. Thromboxane A2 is also a vasoconstrictor andprostacyclin a vasodilator. Several studies have shown that differentdoses of aspirin may swing the haemostatic mechanism in onedirection or the other by altering the balance of platelet aggregatingand aggregation-inhibiting influences. O’Grady and Moncadashowed that 0 - 3 g aspirin prolonged the bleeding time in 6 adult3 Hamashima Y, Kishi K, Tasaka K. Rickettsia like bodies in infantile mucocutaneouslymph node syndrome. Lancet 1973; ii: 42.1. Kato U, Koite S, Yokohama T. Kawasaki disease: effect of treatment on coronary arteryinvolvement. Pediatrics 1979; 63: 175-79.volunteers, whereas 3-9 g g had no effect.2 Masotti et al3 gavedifferent single doses of aspirin to 25 volunteers and measuredmalondialdehyde, platelet aggregation, and prostacyclin levels afterforearm ischaemia at different times. They found that the inhibitionof platelet aggregation was proportional to dose at 2-5 mg/kg andwas barely increased by larger doses, and that prostacyclinproduction was inhibited by larger doses (8 and 10 mg/kg). Largerdoses of aspirin therefore favour platelet aggregation. The durationof inhibition was less than 24 h for prostacyclin and longer than 72 hfor platelet aggregation. The reason for the differential effect isprobably that aspirin acetylates cyclo-oxygenase irreversibly inplatelets but reversibly in blood-vessel walls.4Clearly it would be unwise to rely on studies in healthy adults fortreatment recommendations in ill children with high platelet counts. The present recommendation of 30 mg/kg/day for threemonths is based on work presented at conference proceedings only. 5Further work needs to be done to examine the issue. Until then3’ 5-5 - 0 mg/kg of aspirin every second or third day would seem themost appropriate therapy for these children in the convalescentphase of the illness
- Published
- 1983
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