Document Detail


Clopidogrel with or without omeprazole in coronary artery disease.
MedLine Citation:
PMID:  20925534     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Gastrointestinal complications are an important problem of antithrombotic therapy. Proton-pump inhibitors (PPIs) are believed to decrease the risk of such complications, though no randomized trial has proved this in patients receiving dual antiplatelet therapy. Recently, concerns have been raised about the potential for PPIs to blunt the efficacy of clopidogrel.
METHODS: We randomly assigned patients with an indication for dual antiplatelet therapy to receive clopidogrel in combination with either omeprazole or placebo, in addition to aspirin. The primary gastrointestinal end point was a composite of overt or occult bleeding, symptomatic gastroduodenal ulcers or erosions, obstruction, or perforation. The primary cardiovascular end point was a composite of death from cardiovascular causes, nonfatal myocardial infarction, revascularization, or stroke. The trial was terminated prematurely when the sponsor lost financing.
RESULTS: We planned to enroll about 5000 patients; a total of 3873 were randomly assigned and 3761 were included in analyses. In all, 51 patients had a gastrointestinal event; the event rate was 1.1% with omeprazole and 2.9% with placebo at 180 days (hazard ratio with omeprazole, 0.34, 95% confidence interval [CI], 0.18 to 0.63; P<0.001). The rate of overt upper gastrointestinal bleeding was also reduced with omeprazole as compared with placebo (hazard ratio, 0.13; 95% CI, 0.03 to 0.56; P = 0.001). A total of 109 patients had a cardiovascular event, with event rates of 4.9% with omeprazole and 5.7% with placebo (hazard ratio with omeprazole, 0.99; 95% CI, 0.68 to 1.44; P = 0.96); high-risk subgroups did not show significant heterogeneity. The two groups did not differ significantly in the rate of serious adverse events, though the risk of diarrhea was increased with omeprazole.
CONCLUSIONS: Among patients receiving aspirin and clopidogrel, prophylactic use of a PPI reduced the rate of upper gastrointestinal bleeding. There was no apparent cardiovascular interaction between clopidogrel and omeprazole, but our results do not rule out a clinically meaningful difference in cardiovascular events due to use of a PPI. (Funded by Cogentus Pharmaceuticals; ClinicalTrials.gov number, NCT00557921.).
Authors:
Deepak L Bhatt; Byron L Cryer; Charles F Contant; Marc Cohen; Angel Lanas; Thomas J Schnitzer; Thomas L Shook; Pablo Lapuerta; Mark A Goldsmith; Loren Laine; Benjamin M Scirica; Sabina A Murphy; Christopher P Cannon;
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Publication Detail:
Type:  Clinical Trial, Phase III; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2010-10-06
Journal Detail:
Title:  The New England journal of medicine     Volume:  363     ISSN:  1533-4406     ISO Abbreviation:  N. Engl. J. Med.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-11     Completed Date:  2010-11-30     Revised Date:  2011-10-28    
Medline Journal Info:
Nlm Unique ID:  0255562     Medline TA:  N Engl J Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1909-17     Citation Subset:  AIM; IM    
Affiliation:
Veterans AffairsBoston Healthcare System, Brigham and Women's Hospital, Boston, MA 02132, USA. dlbhattmd@post.harvard.edu
Data Bank Information
Bank Name/Acc. No.:
ClinicalTrials.gov/NCT00557921
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MeSH Terms
Descriptor/Qualifier:
Aged
Aspirin / adverse effects,  therapeutic use
Cardiovascular Diseases / epidemiology
Coronary Artery Disease / drug therapy*
Drug Interactions
Drug Therapy, Combination
Female
Gastrointestinal Hemorrhage / chemically induced,  prevention & control*
Humans
Kaplan-Meier Estimate
Male
Middle Aged
Omeprazole / adverse effects,  therapeutic use*
Platelet Aggregation Inhibitors / adverse effects,  therapeutic use*
Proton Pump Inhibitors / adverse effects,  therapeutic use*
Ticlopidine / adverse effects,  analogs & derivatives*,  therapeutic use
Chemical
Reg. No./Substance:
0/Platelet Aggregation Inhibitors; 0/Proton Pump Inhibitors; 50-78-2/Aspirin; 55142-85-3/Ticlopidine; 73590-58-6/Omeprazole; 90055-48-4/clopidogrel
Investigator
Investigator/Affiliation:
Deepak L Bhatt / ; Byron L Cryer / ; Marc Cohen / ; Angel Lanas / ; Thomas J Schnitzer / ; Robert Giugliano / ; Pim J deFeyter / ; M Brian Fennerty / ; George Triadafilopoulis / ; Robert W Makuch / ; Allen Skene / ; Loren Laine / ; Priya Jamidar / ; Bennie Upchurch / ; Benjamin M Scirica / ; Campbell Joyner / ; Karl Karsch / ; John Amerena / ; Chris Hammett / ; Ian Jeffery / ; Rajesh Kanna / ; Hosen Kiat / ; Nikolina Ganeva / ; Borislav Georgiev / ; Jana Ginkova / ; Assen Goudev / ; Varbitza Hergeldjieva / ; Angel Krastev / ; Atanas Mihov / ; Valentina Mincheva / ; Krastyu Penchev / ; Ivo Petrov / ; Konsatantin Ramshev / ; Snezhanka Tisheva / ; Maria Tokmakova / ; Olivier Bertrand / ; James Cha / ; Danielle Dion / ; John Ducas / ; Kenneth Gin / ; Peter W Klinke / ; Simon Kouz / ; Charles Lefkowitz / ; Claude Maranda / ; Dennis O'Keefe / ; Shekhar Pandey / ; Dennis Rupka / ; Vlad Sluzar / ; Benoit Tremblay / ; Guillermo Araneda / ; Rienzi Díaz / ; Fernando Lanas / ; Lucio León / ; Sergio Potthoff / ; Carlos Raffo / ; Margarita Vejar / ; Mauricio Villavicencio / ; Mario Yañez / ; Dusan Kucera / ; Čestmír Čihalík / ; Milan Dunaj / ; Vladimír Hraboš / ; Zdeněk Monhart / ; Roman Štípal / ; Jan Vojácek / ; Petr Vojtíšek / ; Michel Galinier / ; Ayham Al-Zoebi / ; Christoph Axthelm / ; Clemens Bauknecht / ; Steffen Behrens / ; Hans-Jörg Berger / ; Dietmar Boscher / ; Gunter Claus / ; Wilfried Dänschel / ; Harald Darius / ; Carl-Erik Dempfle / ; Thomas Dorsel / ; Meinrad P Gawaz / ; Sabine Genth-Zotz / ; Gerian Grönefeld / ; Hartmut Guelker / ; Christoph Hahnefeld / ; Hube Heuer / ; Thomas Horacek / ; Thomas Klingenheben / ; Benedikt Kohler / ; Jürgen Kolditz / ; Alfred Krämer / ; Korff Krause / ; Rainer Lange / ; Holger Lawall / ; Michael Oeff / ; Heyder Omran / ; Nicolas Proskynitopoulos / ; Frank Richard / ; Andreas Schreckenberg / ; Thomas Schröder / ; Gerhard Schuler / ; Hans-Otto Schulze / ; Carsten Schwencke / ; Verena Stangl / ; Jürgen Stumpf / ; Jens Taggeselle / ; Peter Uebel / ; Jürgen vom Dahl / ; Eberhardt von Hodenberg / ; Joachim Weil / ; Matthias Weissbrodt / ; Csaba Kerekes / ; Ágnes Kollár / ; Zsolt Kovács / ; Géza Lupkovics / ; László Regos / ; András Vértes / ; Béla Herczeg / ; János Tomcsányi / ; Guido Belli / ; Claudio Brunelli / ; Giuseppe De Luca / ; Giuseppe Musumeci / ; Marco Antonio Alcocer Gamba / ; Ricardo Alvarado Ruíz / ; Jose Luis Leiva Pons / ; Guillermo Llamas Esperón / ; Ulises Rogel Martínez / ; Efraín Villeda Espinosa / ; Małgorzata Biedrzycka / ; Anna Boruczkowska-Kaszkowiak / ; Marek Bronisz / ; Kazimierz Bujak / ; Boguslaw Derlaga / ; Andrzej Drzewiecki / ; Andrzej Gieroba / ; Jarosław Hiczkiewicz / ; Andrzej Hoffmann / ; Maciej Jankowski / ; Krystyna Jaworska / ; Ewa Jazwinska-Tarnawska / ; Barbara Kaczmarek / ; Grzegorz Kania / ; Agnieszka Karczmarc / ; Jacek Karpiński / ; Marek Karpiński / ; Teresa Kawka-Urbanek / ; Piotr Kołodziej / ; Romuald Korzeniak / ; Jarosław Kosior / ; Romuald Krynicki / ; Jacek Kubica / ; Lech Kucharski / ; Piotr Kurek / ; Dorota Kustrzycka-Kratochwil / ; Jerzy Kuzniar / ; Pawel Miękus / ; Ewa Mirek-Bryniarska / ; Franciszek Monies / ; Anna Mrówczyńska / ; Marcin Ogórek / ; Michał Ogórek / ; Bogusław Okopień / ; Artur Oręziak / ; Tomasz Pasierski / ; Marek Piepiorka / ; Władyslaw Pluta / ; Barbara Podogrodzka / ; Lech Polonski / ; Dorota Rogacka / ; Malgorzata Rozycka-Grudniewicz / ; Piotr Ruszkowski / ; Ryszard Ściborski / ; Alicja Stańczak-Krop / ; Roman Szełemej / ; Hanna Szwed / ; Janusz Tarchalski / ; Ryszard Targoński / ; Marek Ujda / ; Przemysław Wilczewski / ; Dariusz Wojciechowski / ; Maciej Zarębiński / ; Gabriel-Petrisor Tatu-Chitoiu / ; Laura Iosipescu / ; Nastase Melicovici / ; Constantin Militaru / ; Stefan Mot / ; Elena Popescu / ; Doina Sipciu / ; Gabriel-Petrisor Tatu-Chitoiu / ; Mariana Tudoran / ; Gabriel Ungureanu / ; Tibor Duris / ; Karol Mičko / ; Daniel Pella / ; Andrej Džupina / ; Veronika Kolíková / ; Iveta Nedelová / ; Roman Oriesek / ; Katarina Škubová / ; Jan Stevlik / ; Darina Straňanková / ; Olena Koval / ; Oleksandr Parkhomenko / ; Oxana Shershnyova / ; Yuriy Sirenko / ; Anatoliy Skrutov / ; Igor Vakaliuk / ; Ivan Vykhovanyuk / ; J Dawn Abbott / ; Ramtin Agah / ; Abdel Ahmed / ; Abdulhay Albirini / ; Anthony Alfieri / ; Mohammad Luay Alkotob / ; George Anagnostis / ; Marshall W Anderson / ; Vikram Arora / ; Subhash Banerjee / ; Steven Barag / ; Gary Bedel / ; Arthur Belber / ; Robert Benton / ; Howard Berlin / ; D Eric Bolster / ; Claude Brachfeld / ; Craig M Brett / ; Chris Brown / ; Curtis Brown / ; Donald Canaday / ; Roddy P Canosa / ; James P Capó / ; Raymond Carlson / ; Kenneth Carr / ; Maria Cartaya / ; Harish Chandna / ; Rajiv Chandra / ; Mark A Chang / ; Richard Charney / ; Rafael Chiong / ; Jules Cohen / ; John Collins / ; Terence Connelly / ; John C Corbelli / ; Brian Cospolich / ; Berge Dadourian / ; Ranjan Dahiya / ; Arthur Daigneault / ; Robert P Dalton / ; Shane Darrah / ; Vikas Desai / ; John Detwiler / ; Sanjay Dhar / ; Pedro Joaquin Diaz / ; Daniel Donovan / ; Salah El Hafi / ; Gary Elkin / ; George Ellis / ; Carlos Fabre / ; Mary Fahrenbach / ; Vincent Figueredo / ; Brian First / ; Tim Fischell / ; Enrique A Flores / ; Robert E Foster / ; Michael Frais / ; William J French / ; Anthony Frey / ; Neal Gaither / ; Lazaro Miguel Garcia / ; Garo Garibian / ; Mark Gelernt / ; Ian Gilchrist / ; Eve Gillespie / ; Harinder Gogia / ; Herbert Goodman / ; Daniel Gottlieb / ; Lachland Goyal / ; Mark W Graves / ; Paul Grena / ; Oscar Guerra / ; Anjan Gupta / ; Hussain Haideri / ; Glenn S Hamroff / ; David Hassel / ; Nancy Hassinger / ; Herbert W Haught / ; John N Herrod / ; Eyal Herzog / ; Cary Hirsch / ; Mark J Holmberg / ; Kevin B Horton / ; Mian A Jan / ; David Jinich / ; Carol Johnson / ; David Johnson / ; Ancil Jones / ; Ameer Kabour / ; David M Kenton / ; Allen Kindman / ; Bruce Klugherz / ; Valli P Kodali / ; Michael J Koren / ; Edward Kosinski / ; Jeffery Kramer / ; Ashok Krishnaswami / ; Mark Kutner / ; Theodore Lau / ; Chao-Wen Lee / ; Jeffery Lins / ; Thomas Little / ; Ramon Lloret / ; Eric Lo / ; Henry K Lui / ; Frank Maggiacomo / ; Amir Malik / ; Peter Mason / ; Stephen Mattichak / ; Elizabeth Mattson / ; Nolan Mayer / ; Darren McGuire / ; Marcus E McKenzie / ; Richard A McLean / ; Anthony Mercando / ; Gary Miller / ; Patrick Moloney / ; Venkatesh Nadar / ; Mani Nallasivan / ; Gavin Noble / ; Julius B Oderinde / ; Stanley Pamfilis / ; Cordel Parris / ; Dharmendra Patel / ; Gregory Pellizzon / ; Richard Perlman / ; Breno Pessanha / ; Annie Peter / ; Arley Peter / ; Roland T Phillips / ; Donna M Polk / ; Dimtcho Popov / ; Steven Promisloff / ; George Raad / ; Abram C Rabinowitz / ; Ganesh Raveendran / ; Carl Rouch / ; Richard Ryder / ; Hani Salha / ; Jay H Sandberg / ; Jasvinder S Sandhu / ; Mark Sanz / ; Devang Savani / ; Aron Schlau / ; Steven Schwartz / ; John F Seaworth / ; Parag Shah / ; Anil Shah / ; Rakesh Shah / ; Nicolas W Shammas / ; Jeffrey Shanes / ; Prateek Sharma / ; Charles R Sharpe / ; David Shavelle / ; Robert M Siegel / ; John Simmons / ; Henry J Simon / ; Rodolfo P Sotolongo / ; John F Speer / ; Sunny Srivastava / ; Lloyd Stahl / ; Cezar Staniloae / ; Dale M Stegeman / ; Ronald Stegemoller / ; Bruce Stein / ; Steven Stoltz / ; Thomas Stuver / ; Parvez K Sultan / ; D P Suresh / ; John E Sutherland / ; Behzad Taghizadeh / ; Jeffrey Tauth / ; Stephen Thew / ; Gregory S Thomas / ; William Tinker / ; John Tretter / ; Samir Turk / ; John Turns / ; Cindy J Tuten / ; Lee Ugol / ; Eric Van De Graaff / ; Jose Vazquez-Tanus / ; Samuel Verzosa / ; Craig Vogel / ; Kishor N Vora / ; Stephen J Voyce / ; William Wainwright / ; Douglas Waldo / ; Peter Wassmer / ; Robert J Weiss / ; Robert J Weiss / ; John Wertheimer / ; Dwayne Williams / ; George Williams / ; Donald M Wood / ; George Yiachos / ; Charles Zacharias / ; Michael Zakrzewski /
Comments/Corrections
Comment In:
N Engl J Med. 2011 Feb 17;364(7):681; author reply 682-3   [PMID:  21323549 ]
N Engl J Med. 2010 Nov 11;363(20):1977   [PMID:  21067412 ]
N Engl J Med. 2011 Feb 17;364(7):681-2; author reply 682-3   [PMID:  21323548 ]
Evid Based Med. 2011 Oct;16(5):144-5   [PMID:  21558563 ]
Ann Intern Med. 2011 Mar 15;154(6):JC3-7   [PMID:  21403070 ]
Intern Emerg Med. 2011 Apr;6(2):159-60   [PMID:  21369851 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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