Document Detail


Dose comparisons of clopidogrel and aspirin in acute coronary syndromes.
MedLine Citation:
PMID:  20818903     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Clopidogrel and aspirin are widely used for patients with acute coronary syndromes and those undergoing percutaneous coronary intervention (PCI). However, evidence-based guidelines for dosing have not been established for either agent.
METHODS: We randomly assigned, in a 2-by-2 factorial design, 25,086 patients with an acute coronary syndrome who were referred for an invasive strategy to either double-dose clopidogrel (a 600-mg loading dose on day 1, followed by 150 mg daily for 6 days and 75 mg daily thereafter) or standard-dose clopidogrel (a 300-mg loading dose and 75 mg daily thereafter) and either higher-dose aspirin (300 to 325 mg daily) or lower-dose aspirin (75 to 100 mg daily). The primary outcome was cardiovascular death, myocardial infarction, or stroke at 30 days.
RESULTS: The primary outcome occurred in 4.2% of patients assigned to double-dose clopidogrel as compared with 4.4% assigned to standard-dose clopidogrel (hazard ratio, 0.94; 95% confidence interval [CI], 0.83 to 1.06; P=0.30). Major bleeding occurred in 2.5% of patients in the double-dose group and in 2.0% in the standard-dose group (hazard ratio, 1.24; 95% CI, 1.05 to 1.46; P=0.01). Double-dose clopidogrel was associated with a significant reduction in the secondary outcome of stent thrombosis among the 17,263 patients who underwent PCI (1.6% vs. 2.3%; hazard ratio, 0.68; 95% CI, 0.55 to 0.85; P=0.001). There was no significant difference between higher-dose and lower-dose aspirin with respect to the primary outcome (4.2% vs. 4.4%; hazard ratio, 0.97; 95% CI, 0.86 to 1.09; P=0.61) or major bleeding (2.3% vs. 2.3%; hazard ratio, 0.99; 95% CI, 0.84 to 1.17; P=0.90).
CONCLUSIONS: In patients with an acute coronary syndrome who were referred for an invasive strategy, there was no significant difference between a 7-day, double-dose clopidogrel regimen and the standard-dose regimen, or between higher-dose aspirin and lower-dose aspirin, with respect to the primary outcome of cardiovascular death, myocardial infarction, or stroke. (Funded by Sanofi-Aventis and Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00335452.)
Authors:
; Shamir R Mehta; Jean-Pierre Bassand; Susan Chrolavicius; Rafael Diaz; John W Eikelboom; Keith A A Fox; Christopher B Granger; Sanjit Jolly; Campbell D Joyner; Hans-Jurgen Rupprecht; Petr Widimsky; Rizwan Afzal; Janice Pogue; Salim Yusuf
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Publication Detail:
Type:  Comparative Study; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The New England journal of medicine     Volume:  363     ISSN:  1533-4406     ISO Abbreviation:  N. Engl. J. Med.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-09-07     Completed Date:  2010-09-16     Revised Date:  2011-02-04    
Medline Journal Info:
Nlm Unique ID:  0255562     Medline TA:  N Engl J Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  930-42     Citation Subset:  AIM; IM    
Data Bank Information
Bank Name/Acc. No.:
ClinicalTrials.gov/NCT00335452
Export Citation:
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MeSH Terms
Descriptor/Qualifier:
Acute Coronary Syndrome / drug therapy*,  mortality,  therapy
Aged
Angioplasty, Balloon, Coronary
Aspirin / administration & dosage*,  adverse effects
Cardiovascular Diseases / mortality,  prevention & control
Combined Modality Therapy
Coronary Angiography
Coronary Artery Bypass
Double-Blind Method
Female
Hemorrhage / chemically induced,  mortality
Humans
Kaplan-Meier Estimate
Male
Middle Aged
Myocardial Infarction / epidemiology
Platelet Aggregation Inhibitors / administration & dosage*,  adverse effects
Research Design
Stroke / epidemiology
Ticlopidine / administration & dosage,  adverse effects,  analogs & derivatives*
Chemical
Reg. No./Substance:
0/Platelet Aggregation Inhibitors; 50-78-2/Aspirin; 55142-85-3/Ticlopidine; 90055-48-4/clopidogrel
Investigator
Investigator/Affiliation:
S R Mehta / ; S Yusuf / ; S Chrolavicius / ; A E Ajani / ; A Avezum / ; J P Bassand / ; W E Boden / ; A Budaj / ; E G Cardona-Muñoz / ; J Col / ; P J Commerford / ; G Di Pasquale / ; R Diaz / ; J Eha / ; J W Eikelboom / ; D P Faxon / ; M Flather / ; D Foley / ; K A A Fox / ; M G Franzosi / ; C B Granger / ; M Gupta / ; S Jolly / ; C Joyner / ; N Karatzas / ; A Kastrati / ; J H Kim / ; T H Koh / ; F Lanas / ; B Lewis / ; C Macaya / ; T Moccetti / ; G Montalescot / ; K O Niemelä / ; Z Ongen / ; A Orlandini / ; P Pais / ; R J G Peters / ; L Piegas / ; J Probstfield / ; J M Rankin / ; M Ruda / ; Z Rumboldt / ; H J Rupprecht / ; P G Steg / ; J F Tanguay / ; V Valentin / ; J Varigos / ; H D White / ; P Widimsky / ; D Xavier / ; J Zhu / ; J R Zhu / ; C Gaudin / ; C Marchese / ; C Bouancheau / ; M Blumenthal / ; P Hornick / ; R Saini / ; M Atra / ; K Bainey / ; A Barsan / ; I Benedek / ; G Borislav / ; N Bornstein / ; Y Cottin / ; A Czepiel / ; H DeRaedt / ; M Dorobantu / ; G Fodor / ; E Gardinale / ; B Gross / ; H Guimaraes / ; D Halon / ; O Happola / ; J Hartikainen / ; D Himbert / ; Q Hua / ; S S Iyengar / ; P Kalvach / ; B Kies / ; C J Kim / ; M Laine / ; S Lang / ; A Maggioni / ; A Massaro / ; C Morillo / ; J Narendra / ; U Naslund / ; Y Nisanci / ; T Okay / ; A Peeters / ; M Penicka / ; A Perakis / ; A Piplis / ; G Pizzolato / ; S Polic / ; J Renkin / ; M Rokoss / ; N Runev / ; A Siva / ; E Sorokin / ; B Stockins / ; F Turrazza / ; N Valettas / ; Y Yang / ; J Zaborski / ; R Zimlichman / ; P Sleight / ; J L Anderson / ; D L DeMets / ; J Hirsh / ; D R Holmes / ; D E Johnstone / ; B Jedrzejowski / ; A Robinson / ; M Lawrence / ; J Pogue / ; R Afzal / ; L Blake / ; W Chen / ; S Di Diodato / ; R Manojlovic / ; L Mastrangelo / ; A Mead / ; E Pasadyn / ; T Sovereign / ; L Wasala / ; M Amuchastegui / ; M H Bustamante Labarta / ; G D Caime / ; L Cartasegna / ; G R Covelli / ; J J Fuselli / ; M A Garrido / ; L R Grinfeld / ; M A Hominal / ; A D Hrabar / ; G B Labarta / ; A J Licheri / ; L L Lobo Marquez / ; H L Luciardi / ; C R Majul / ; J C Pomposiello / ; A D Prado / ; A O Rodriguez / ; S Salzberg / ; A S Sanchez / ; D A Santos / ; P O Schygiel / ; G O Zapata / ; M Arstall / ; M F Binnekamp / ; D Brieger / ; D M Colquhoun / ; D S Eccleston / ; S Hale / ; R Hendriks / ; A T Hill / ; S Ruane / ; B B Singh / ; P L Thompson / ; S J Thompson / ; W Walsh / ; M I Worthley / ; G Delle-Karth / ; K Huber / ; C Beauloye / ; V Dangoisse / ; L Janssens / ; S Janssens / ; O Marcovitch / ; P E Massart / ; M Vincent / ; M C Vrolix / ; J Abrantes / ; W R Ardito / ; A C Baruzzi / ; R V Botelho / ; J K R Carneiro / ; A C Carvalho / ; M Coutinho / ; O Dutra / ; C P Jaeger / ; A P M Kormann / ; L N Maia / ; E Manenti / ; J A Mangione / ; J A Marin-Neto / ; R L Marino / ; A C Markman / ; S A Mendonça / ; R D Mora / ; M S M Paiva / ; C A Polanczyk / ; A Rabelo / ; G Reis / ; H L Reis / ; P R Rossi / ; W F Saporito / ; J F K Saraiva / ; A C S Sousa / ; A Timerman / ; R T Tumelero / ; A R Doganov / ; G V Grigorov / ; M V Grigorov / ; J B Jorgova / ; I H Manukov / ; A S Postadzhiyan / ; P Béliveau / ; J C Berlingieri / ; D Borts / ; S W Brons / ; J R Burton / ; Y K Chan / ; C T Cockhill / ; C Constance / ; J P Déry / ; V Dzavik / ; D A Fell / ; D H Fitchett / ; A Y Fung / ; G Gosselin / ; F Hussain / ; T Huynh / ; C V Kieu / ; G C MacCallum / ; M Madan / ; M Montigny / ; F Nigro / ; S Pallie / ; J P Pelletier / ; D C Phaneuf / ; O Salehian / ; E Schampaert / ; M Senaratne / ; S Shariff / ; I Singh / ; J A Syed / ; M E Alcaino / ; E Garcés / ; R Lamich / ; A P Lichter / ; M Lopetegui / ; L A Perez / ; P A Sepulveda / ; J Y Chen / ; Y D Chen / ; G S Fu / ; J B Ge / ; Y L Han / ; B He / ; Y N Ke / ; H W Li / ; T C Li / ; W J Li / ; W M Li / ; Z Q Li / ; S Z Lv / ; G S Ma / ; G X Qi / ; S B Qiao / ; Y X Sun / ; D W Wang / ; J A Wang / ; X Wang / ; M Wei / ; B Xu / ; T L Yang / ; X C Yang / ; Z Y Yuan / ; S Y Zhang / ; J H Zhu / ; M Bergovec / ; J Mirat / ; M Padovan / ; P Samardzic / ; O Aschermann / ; M Branny / ; P Cervinka / ; Z Coufal / ; J Dvorak / ; K Gorican / ; P Hajek / ; P Jelínek / ; P Kala / ; G Marcinek / ; M Oscipovský / ; M Padour / ; M Richter / ; R Rokyta / ; R Spacek / ; D Vencour / ; J Vojacek / ; K E J Airaksinen / ; M J Niemela / ; S Vikman / ; L Belle / ; C Caussin / ; G Ducrocq / ; E Ferrari / ; R P Fouché / ; G P Geslin / ; P Lim / ; G Pacouret / ; F Schiele / ; K F Appel / ; I Atmowihardjo / ; J Brachmann / ; M Buerke / ; W Burkhardt / ; M P Desaga / ; S Fichtlscherer / ; D Fischer / ; S Genth-Zotz / ; S Hoffmann / ; V Klauss / ; C A Nienaber / ; C M Nuellen / ; A E Schmidt / ; W A Schoebel / ; H Schunkert / ; P Schwimmbeck / ; R H Strasser / ; J Vom Dahl / ; E Von Hodenberg / ; R Willenbrock / ; R J Zotz / ; D Alexopoulos / ; J N Nanas / ; H A Baxi / ; M Bhaskara Rao / ; V Bhatia / ; P Chandwani / ; S Dwivedi / ; K K Haridas / ; R K Jain / ; P G Kerkar / ; U K Mahorkar / ; K H Parikh / ; T M Patel / ; B V Pinto / ; A Puri / ; S S Ramesh / ; V S P Rao / ; J P S Sawhney / ; K P Shetty / ; N Sinha / ; A Srinivas / ; R K Tongia / ; S K Trivedi / ; S N Vaishnav / ; S Varma / ; P A Crean / ; J J Crowley / ; H McCann / ; F McGrath / ; J Arbel / ; A Finkelstein / ; S Halabi / ; M Halabi / ; A Marmor / ; S R Meisel / ; A Pollak / ; A Porter / ; E Rechavia / ; Y Rozenman / ; Y Turgeman / ; A T Weiss / ; L Bolognese / ; F Bovenzi / ; C Cavallini / ; F Chiarella / ; G De Luca / ; M Galli / ; M Galvani / ; C Greco / ; M Lettino / ; U Limbruno / ; P Meneghetti / ; D Nassiacos / ; R Pes / ; G Piovaccari / ; S Pirelli / ; M L Rossi / ; A Salvioni / ; G Steffenino / ; S Tredici / ; R Zanini / ; A Erglis / ; V Joksas / ; R Unikas / ; W P Chong / ; A Y Y Fong / ; C Y Lee / ; R Zambahari / ; J L Arenas / ; D Cardona-Müller / ; M Ledesma / ; P H Dunselman / ; J P R Herrman / ; H R Michels / ; J M ten Berg / ; J R Benatar / ; G P Devlin / ; J M Elliott / ; S A Harding / ; H Patel / ; D S Scott / ; G T Wilkins / ; P E Buszman / ; M Dalkowski / ; A Drzewiecki / ; J Gessek / ; R J Gil / ; J J Hiczkiewicz / ; K Jaworska / ; Z Kalarus / ; P Kardaszewicz / ; D Kawecki / ; J F Kopaczewski / ; Z Kornacewicz-Jach / ; J Kubica / ; J Kuźniar / ; P Miekus / ; W J Musiał / ; A Rynkiewicz / ; S Trznadel / ; D Winek / ; A S Włodarczyk / ; B Wrzosek / ; E Zinka / ; T M Benedek / ; R Capalneanu / ; S I Dragulescu / ; C Ginghina / ; R A Onut / ; S A Berns / ; E G Fokina / ; A K Gruzdev / ; S G Kalinina / ; E D Kosmachova / ; V A Markov / ; S H Ewe / ; P Kurray / ; M Studencan / ; A Chin / ; H D Theron / ; J M Cho / ; K H Choe / ; N S Chung / ; S H Her / ; M H Jeong / ; D S Kim / ; H S Kim / ; M H Kim / ; S K Kim / ; Y K Kim / ; S W Park / ; C Y Rhim / ; E K Shin / ; A Albarran / ; J Angel / ; P Avanzas / ; F Bosa / ; G Calle / ; A R Cequier / ; J M Cubero / ; A Delcastillo / ; J F Diaz / ; J Fdez Portales / ; A Fernandez-Ortiz / ; J M Hernández-García / ; L F Iglesias / ; I Lekuona / ; R Lopez-Palop / ; M Masotti / ; F Picó-Aracil / ; M Puigfel / ; M Sabate / ; M A Suarez / ; N Vazquez Gonzalez / ; J D Herlitz / ; A Hot-Bjelak / ; P Erne / ; R Hille / ; P F Keller / ; H Rickli / ; M G Rossi / ; A Abaci / ; G G Bozkurt / ; I Erdinler / ; T Gürmen / ; M Sahin / ; A Baumbach / ; A J De Belder / ; D A Gorog / ; G Manoharan / ; D Smith / ; R J Acheatel / ; M K Ariani / ; S R Bailey / ; E R Bates / ; R S Bhagwat / ; D Bohle / ; J E B Burchenal / ; J W Chambers / ; H Chandna / ; Y S Chandrashekhar / ; H B Cheek / ; B S Clemson / ; R C Dewey / ; D H Drenning / ; R Ebrahimi / ; P S Fail / ; G J Fishbein / ; S J Fitzmorris / ; S L Goldberg / ; K J Habet / ; C D Hassel / ; M R Izzo / ; M M Karve / ; J Kieval / ; B D Klugherz / ; G Larrain / ; W E Lawson / ; M Leesar / ; E L-S Lo / ; K Lohavanichbutr / ; J T Maddux / ; J H Magno / ; E Mahmud / ; S N Makam / ; J T Mann / ; R C Marsh / ; S J Marshalko / ; J Martinez-Arraras / ; J P Massaro / ; K Mavromatis / ; N J Mayer / ; B A McLellan / ; J A McPherson / ; A N Mooss / ; E Mostel / ; V K Nadar / ; S T Palmeri / ; P Pandey / ; V Pasnoori / ; A Pothula / ; R Prashad / ; G J Reis / ; E Rivera / ; D M Safley / ; R M Santos / ; J W Schoondyke / ; A A Shakir / ; M K Sharma / ; M F Shoukfeh / ; N Singh / ; C R Smith / ; S M Stoltz / ; J Strain / ; W A Tan / ; H M Thai / ; S T Thew / ; P N Ver Lee / ; R M Vicari / ; W F Voyles / ; J S Walder / ; C L Wolfe / ; W C L Wu /
Comments/Corrections
Comment In:
Expert Opin Pharmacother. 2011 Jan;12(1):149-51   [PMID:  21108602 ]
Ann Intern Med. 2011 Jan 18;154(2):JC1-7   [PMID:  21242361 ]
N Engl J Med. 2010 Dec 16;363(25):2466; author reply 2467-8   [PMID:  21158666 ]
N Engl J Med. 2010 Dec 16;363(25):2465-6; author reply 2467-8   [PMID:  21158667 ]
N Engl J Med. 2010 Sep 2;363(10):976-7   [PMID:  20818910 ]
N Engl J Med. 2010 Dec 16;363(25):2466-7; author reply 2467-8   [PMID:  21158665 ]
Erratum In:
N Engl J Med. 2010 Oct 14;363(16):1585

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