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Your search keyword '"Aspirin/administration & dosage"' showing total 13 results
Start Over Descriptor "Aspirin/administration & dosage" Topic general medicine
13 results on '"Aspirin/administration & dosage"'

1. Low-dose aspirin for the prevention of preterm birth: More questions than answers

Author

Sarah Jane Stock and Victoria Hodgetts Morton

Subjects
Premature Birth/epidemiology, Randomized Controlled Trials as Topic/methods, Anti-Inflammatory Agents, Non-Steroidal/administration & dosage, Pregnancy, Pre-Eclampsia/epidemiology, Infant, Newborn, Humans, Medicine, Female, General Medicine, Abortion, Habitual/epidemiology, Aspirin/administration & dosage
Published
2022

2. Two common mild analgesics have no effect on general endocrine mediated endpoints in zebrafish (Danio rerio)

Author

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

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

Author

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

Subjects
Carotid Artery Diseases, Male, Myocardial Infarction, MESH: Lower Extremity, 030204 cardiovascular system & hematology, THERAPY, Stroke/epidemiology, MESH: Dose-Response Relationship, Drug, 0302 clinical medicine, Rivaroxaban, prevention, Hemorrhage/chemically induced, MESH: Peripheral Arterial Disease, MESH: Double-Blind Method, guidelines, MESH: Incidence, 030212 general & internal medicine, Cardiovascular Diseases/mortality, risk, RISK, MESH: Aged, MESH: Middle Aged, Incidence, General Medicine, Middle Aged, 3. Good health, Stroke, MESH: Myocardial Infarction, Lower Extremity, Cardiovascular Diseases, MESH: Platelet Aggregation Inhibitors, Factor Xa Inhibitors/administration & dosage, Drug Therapy, Combination, Female, MESH: Factor Xa Inhibitors, OUTPATIENTS, MESH: Rivaroxaban, management, MESH: Hemorrhage, metaanalysis, Lower Extremity/blood supply, Rivaroxaban/administration & dosage, Hemorrhage, MESH: Drug Administration Schedule, Amputation, Surgical, Drug Administration Schedule, MESH: Stroke, Peripheral Arterial Disease, 03 medical and health sciences, Double-Blind Method, atherothrombosis, Myocardial Infarction/epidemiology, MANAGEMENT, Humans, MESH: Amputation, MESH: Aspirin, Aspirin/administration & dosage, Platelet Aggregation Inhibitors/administration & dosage, METAANALYSIS, Aged, MESH: Humans, Aspirin, Dose-Response Relationship, Drug, MESH: Carotid Artery Diseases, MORTALITY, MESH: Cardiovascular Diseases, cardiovascular event rates, PREVENTION, CARDIOVASCULAR EVENT RATES, MESH: Male, outpatients, atrial-fibrillation, MESH: Drug Therapy, Combination, MESH: Morbidity, Carotid Artery Diseases/complications, lower-extremity amputation, Peripheral Arterial Disease/complications, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Morbidity, MESH: Female, Platelet Aggregation Inhibitors, Amputation/statistics & numerical data, Factor Xa Inhibitors
Abstract

BACKGROUND: Patients with peripheral artery disease have an increased risk of cardiovascular morbidity and mortality. Antiplatelet agents are widely used to reduce these complications.METHODS: This was a multicentre, double-blind, randomised placebo-controlled trial for which patients were recruited at 602 hospitals, clinics, or community practices from 33 countries across six continents. Eligible patients had a history of peripheral artery disease of the lower extremities (previous peripheral bypass surgery or angioplasty, limb or foot amputation, intermittent claudication with objective evidence of peripheral artery disease), of the carotid arteries (previous carotid artery revascularisation or asymptomatic carotid artery stenosis of at least 50%), or coronary artery disease with an ankle-brachial index of less than 0·90. After a 30-day run-in period, patients were randomly assigned (1:1:1) to receive oral rivaroxaban (2·5 mg twice a day) plus aspirin (100 mg once a day), rivaroxaban twice a day (5 mg with aspirin placebo once a day), or to aspirin once a day (100 mg and rivaroxaban placebo twice a day). Randomisation was computer generated. Each treatment group was double dummy, and the patient, investigators, and central study staff were masked to treatment allocation. The primary outcome was cardiovascular death, myocardial infarction or stroke; the primary peripheral artery disease outcome was major adverse limb events including major amputation. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants.FINDINGS: Between March 12, 2013, and May 10, 2016, we enrolled 7470 patients with peripheral artery disease from 558 centres. The combination of rivaroxaban plus aspirin compared with aspirin alone reduced the composite endpoint of cardiovascular death, myocardial infarction, or stroke (126 [5%] of 2492 vs 174 [7%] of 2504; hazard ratio [HR] 0·72, 95% CI 0·57-0·90, p=0·0047), and major adverse limb events including major amputation (32 [1%] vs 60 [2%]; HR 0·54 95% CI 0·35-0·82, p=0·0037). Rivaroxaban 5 mg twice a day compared with aspirin alone did not significantly reduce the composite endpoint (149 [6%] of 2474 vs 174 [7%] of 2504; HR 0·86, 95% CI 0·69-1·08, p=0·19), but reduced major adverse limb events including major amputation (40 [2%] vs 60 [2%]; HR 0·67, 95% CI 0·45-1·00, p=0·05). The median duration of treatment was 21 months. The use of the rivaroxaban plus aspirin combination increased major bleeding compared with the aspirin alone group (77 [3%] of 2492 vs 48 [2%] of 2504; HR 1·61, 95% CI 1·12-2·31, p=0·0089), which was mainly gastrointestinal. Similarly, major bleeding occurred in 79 (3%) of 2474 patients with rivaroxaban 5 mg, and in 48 (2%) of 2504 in the aspirin alone group (HR 1·68, 95% CI 1·17-2·40; p=0·0043).INTERPRETATION: Low-dose rivaroxaban taken twice a day plus aspirin once a day reduced major adverse cardiovascular and limb events when compared with aspirin alone. Although major bleeding was increased, fatal or critical organ bleeding was not. This combination therapy represents an important advance in the management of patients with peripheral artery disease. Rivaroxaban alone did not significantly reduce major adverse cardiovascular events compared with asprin alone, but reduced major adverse limb events and increased major bleeding.FUNDING: Bayer AG.

Published
2018

4. Dabigatran for Prevention of Stroke after Embolic Stroke of Undetermined Source

Author

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

Subjects
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.).

Published
2019

5. Use of low-dose aspirin and mortality after prostate cancer diagnosis:A nationwide cohort study

Author

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

Subjects
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.

Published
2019

6. Rationale, design and baseline characteristics of the effect of ticagrelor on health outcomes in diabetes mellitus patients Intervention study

Author

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

Subjects
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

Published
2019

7. Gender and age differences in outcomes of patients with acute coronary syndromes referred for coronary angiography

Author

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

Subjects
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.

Published
2019
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8. Rivaroxaban with or without aspirin in patients with stable coronary artery disease : an international, randomised, double-blind, placebo-controlled trial

Author

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

Subjects
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

9. Rivaroxaban or Aspirin for Extended Treatment of Venous Thromboembolism

Author

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.

Subjects
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

10. Enteric coating can lead to reduced antiplatelet effect of low-dose acetylsalicylic acid

Author

Dorte Ejg Jarbøl, Peter Haastrup, and Thor Grønlykke

Subjects
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

11. 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

Author

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

12. Aspirin plus ticlopidine prevented experimental endocarditis due toEnterococcus faecalisandStreptococcus gallolyticus

Author

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

13. 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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