Background: The primary aim of this article was to explore, in subgroup analyses, whether participants with differing frequencies of aspirin consumption in a randomized, double-blind, placebo-controlled, primary prevention trial had different magnitudes of benefit in the prevention of myocardial infarction. Secondary aims were to identify factors associated with adherence and to examine the relationship of adherence with cardiovascular outcomes in the placebo group.
Methods: The Physicians' Health Study randomized 22071 US male physicians who were free of myocardial infarction and cerebrovascular disease at baseline. The average follow-up during the aspirin component of the trial was 60.2 months. Baseline cardiovascular risk factors and adherence to therapy during the trial were assessed by questionnaire; cardiovascular outcomes were reported by questionnaire and confirmed by record review by an Endpoints Committee.
Results: Several cardiovascular disease risk factors assessed at baseline were related to poor adherence (taking < 50% of study tablets): cigarette smoking, obesity, lack of exercise, and history of angina. After adjusting for baseline differences in risk factors, participants in the aspirin group with excellent adherence (taking at least 95% of study tablets) had a statistically significant 51% reduction in myocardial infarction compared with those with excellent adherence in the placebo group. Those in the aspirin group with poor adherence had a smaller, non-significant reduction in risk of myocardial infarction (a 17% reduction associated with taking < 50% of study tablets). In the placebo group better adherence was not associated with decreased risk of myocardial infarction, but was strongly associated with decreased risk of death.
Conclusions: These subgroup data raise the possibility that a less than alternate day aspirin regimen may yield lower benefits in the prevention of myocardial infarction. Alternate explanations are that these analyses reflect either the play of chance or effects of uncontrolled confounding since comparisons were no longer randomized. Randomized trials are necessary to address the question of frequency of administration of aspirin to achieve optimal benefits in primary prevention of myocardial infarction.