Letter by Kurth Regarding Article, “Nonsteroidal Antiinflammatory Drugs, Acetaminophen, and the Risk of Cardiovascular Events”
To the Editor:
The study by Chan and colleagues1 evaluated the association between use of nonsteroidal antiinflammatory drugs (NSAIDs) and acetaminophen and the risk of major cardiovascular disease in apparently healthy women. Their study showed a statistically significant increased risk among women who used NSAIDs or acetaminophen ≥22 days per month. In their discussion, the authors cited a secondary analysis from the Physicians’ Health Study that regular NSAID use (use of NSAIDS ≥60 days per year) was associated with a nearly 3-fold higher risk of myocardial infarction among men randomly assigned to aspirin as supportive evidence that NSAID use is associated with increased risk of myocardial infarction. In this analysis,2 however, the authors were only evaluating whether concomitant use of NSAIDs modifies the beneficial effect of aspirin on first myocardial infarction. Specifically, this finding must be considered in the context of other Physicians’ Health Study results. The main finding of the Physicians’ Health Study was a highly statistically significant 44% reduction in risk of first myocardial infarction for men randomly assigned to 325 mg aspirin every other day compared with men randomly assigned to placebo.3 On the basis of a biologically plausible mechanism,4 we evaluated in secondary analyses whether NSAID use inhibits this beneficial effect. We found that the relative risk of myocardial infarction was 1.57 (95% confidence interval, 0.70 to 3.56) for men assigned to aspirin who initiated use of NSAIDs ≥60 days per year and 0.21 (95% confidence interval, 0.03 to 1.50) for men assigned to placebo who additionally used NSAIDs ≥60 days per year when compared with men assigned to placebo who did not initiate any NSAID use.2 Thus, the risk reduction of myocardial infarction by aspirin was not apparent among those men assigned to aspirin who initiated NSAIDs ≥60 days per year. Taking this result into consideration, it would be expected that in stratified analyses, men randomly assigned to aspirin who concomitantly used NSAIDs regularly would have an apparent increased risk of myocardial infarction, as NSAID users were compared with men who had the biggest benefit (that is, those randomly assigned to aspirin who did not initiate any NSAID use). Thus, the result of the secondary analyses of the Physicians’ Health Study does not suggest that NSAID use is associated with increased risk of myocardial infarction among men randomly assigned to aspirin but rather that regular NSAID use inhibited the clinical benefit of aspirin on first myocardial infarction.2
Dr Kurth has received investigator-initiated, research grants from Bayer AG, McNeil Consumer & Specialty Pharmaceuticals, and Wyeth Consumer Healthcare.
Chan AT, Manson JE, Albert CM, Chea CU, Rexrode KM, Curhan GC, Rimm EB, Willett WC, Fuchs CS. Nonsteroidal antiinflammatory drugs, acetaminophen, and the risk of cardiovascular events. Circulation. 2006; 113: 1578–1587.
Kurth T, Glynn RJ, Walker AM, Chan KA, Buring JE, Hennekens CH, Gaziano JM. Inhibition of clinical benefits of aspirin on first myocardial infarction by nonsteroidal antiinflammatory drugs. Circulation. 2003; 108: 1191–1195.