As with many therapies in modern medicine, aspirin for the primary prevention of atherosclerotic cardiovascular disease (ASCVD) is neither all good nor all bad. Specifically, aspirin may benefit selected patients, but that comes at the price of a narrower therapeutic window than desirable because of the risks of major bleeding, particularly intracranial and gastrointestinal hemorrhage.
Bolstered by favorable results in tertiary and secondary ASCVD prevention trials in the 1980s, the early trials of aspirin in primary prevention also appeared favorable. For example, in the Physicians’ Health Study of men, treatment with 325 mg of aspirin every other day reduced myocardial infarction (MI) incidence by 44%. More importantly, this represented differential rates of MI of 0.25% per year in the aspirin group vs 0.44% in the placebo group, for a 5-year difference of 0.93% and a number needed to treat for 5 years of approximately 100 to prevent 1 MI.1 A subsequent trial in women health care professionals2 demonstrated no significant benefit for major cardiovascular disease (CVD) events but demonstrated a significant reduction in ischemic stroke. In both trials and others, there were signals of small absolute increases in risk for major bleeding. Countless meta-analyses of the many early trials saw the pendulum swing back and forth on aspirin benefits and harms, with most guidelines favoring use of aspirin in higher-risk primary prevention patients who had no elevated risk of bleeding.
Indeed, the 2016 recommendations from the US Preventive Services Task Force (USPSTF)3 reflected these syntheses in the context of absolute benefits and absolute risks. At that time, the USPSTF gave a grade B recommendation (Table) for primary prevention of CVD in adults aged 50 to 59 years at elevated CVD risk and without risk for bleeding and a grade C recommendation to individualize decisions for adults aged 60 to 69 years at elevated risk. The USPSTF judged that the evidence was insufficient to make recommendations for adults younger than 50 years or older than 69 years. Whereas these recommendations were evidence-based and sound, clinicians may have felt uncertain how to weigh potential risks and benefits for individual patients.