Aspirin dose >81mg daily not beneficial for secondary prevention of CVD

Clinical Question

What is the optimal dose of aspirin for secondary prevention of stroke or myocardial infarction?

Bottom Line

In this systematic review of 11 studies including more than 41,000 patients no evidence was found to support aspirin doses above 81mg for the secondary prevention of stroke or myocardial infarction. In addition, higher doses of aspirin are likely to increase the risk of major bleeding. (LOE = 1a-)


Campbell CL, Smyth S, Montalescot G, Steinhubl SR. Aspirin dose for the prevention of cardiovascular disease: A systematic review. JAMA 2007;297:2018-2024.  [PMID:17488967]

Study Design

Systematic review


Unknown/not stated


Various (meta-analysis)


Approximately one third of the US adult population takes aspirin daily for the prevention of cardiovascular disease; pharmaceutical research suggests that 60% take 81 mg and 35% take 325 mg. These authors conducted a systematic review of the literature to determine the optimal dose of aspirin for the secondary prevention of cardiovascular disease. The authors searched MEDLINE, EMBASE, and bibliographies to identify 11 studies: 8 randomized controlled trials (RCTs) and 3 observational studies enrolling more than 41,000 patients. Although no attempts were made to locate unpublished data, it is unlikely that enough of such trials exist to change these results. Some of the studies enrolled patients after stroke or transient ischemic attack; the remaining studies enrolled patients after myocardial infarction (MI). End points included death and major cardiovascular events. None of the 11 studies showed any benefit to increasing aspirin dose above 81mg daily. Interestingly, 2 prospective trials actually showed increased rates of death, MI, or stroke in patients taking higher doses of aspirin. The authors also reviewed the literature on adverse effects of aspirin. Three RCTs and one meta-analysis demonstrated an increased risk of bleeding with higher doses of aspirin. One subsequent meta-analysis failed to show any relationship between aspirin dose and gastrointestinal bleeding. Nevertheless, given the lack of benefit and possible risk of higher doses, this information is likely relevant to point-of-care decision making.