Document Detail


Hypothesis formulation from subgroup analyses: nonadherence or nonsteroidal anti-inflammatory drug use explains the lack of clinical benefit of aspirin on first myocardial infarction attributed to "aspirin resistance".
MedLine Citation:
PMID:  20435181     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: "Aspirin resistance" has been defined as the occurrence of cardiovascular events despite regular intake of aspirin. One major analytic study suggesting that "aspirin resistance" is a clinical reality was unable to control for confounding by nonadherence or nonsteroidal anti-inflammatory drugs (NSAIDs). METHODS: We formulated a hypothesis from subgroup analyses in the Physicians' Health Study, a randomized double-blind placebo-controlled trial testing 325 mg of aspirin every other day among 22,071 apparently healthy US male physicians. We classified participants by nonadherence or NSAIDs and used time-varying Cox proportional hazard models to adjust for confounding. RESULTS: After 5 years, the blinded aspirin component was terminated early based on the unanimous recommendation of the Data and Safety Monitoring Board. Of 378 confirmed first myocardial infarctions (139 aspirin and 239 placebo), the relative risk (RR) was 0.56 (95% CI 0.45-0.70, P < .00001). There was no statistically significant reduction among aspirin <150/180 pills/y (RR = 0.91, 95% CI 0.61-1.35, P = .62) or NSAID users >60 days per year (RR = 1.54, 95% CI 0.68-3.47, P = .31). There was a statistically significant reduction among aspirin >150/180 pills/y and NSAID users <60 days/y (RR = 0.55, 95% CI 0.44-0.70, P < or = .0001) and an increase among aspirin <150/180 pills/y and NSAID users >60 days/y (RR of 3.43, 95% CI 1.41-8.33, P = .007). CONCLUSIONS: In subgroup analyses useful to formulate hypotheses from a large randomized trial in apparently healthy men, aspirin nonadherence or NSAID use explained the lack of clinical benefit of aspirin on first myocardial infarction that has been attributed to "aspirin resistance." Direct randomized comparisons are necessary in trials designed a priori to test this hypothesis.
Authors:
Charles H Hennekens; Wendy R Schneider; Patricia R Hebert; Udaya S Tantry; Paul A Gurbel
Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  American heart journal     Volume:  159     ISSN:  1097-6744     ISO Abbreviation:  Am. Heart J.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-05-03     Completed Date:  2010-05-24     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0370465     Medline TA:  Am Heart J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  744-8     Citation Subset:  AIM; IM    
Copyright Information:
2010 Mosby, Inc. All rights reserved.
Affiliation:
Florida Atlantic University, Boca Raton, 33431-0991, USA. profchhmd@prodigy.net
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Aged, 80 and over
Anti-Inflammatory Agents, Non-Steroidal / pharmacology
Aspirin / pharmacology
Drug Tolerance
Humans
Male
Middle Aged
Myocardial Infarction / prevention & control
Patient Compliance*
Proportional Hazards Models
Chemical
Reg. No./Substance:
0/Anti-Inflammatory Agents, Non-Steroidal; 50-78-2/Aspirin
Comments/Corrections
Comment In:
Am Heart J. 2010 May;159(5):713-5   [PMID:  20435177 ]

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


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