Multiple randomized clinical trials have established that aspirin reduces the incidence of stroke and myocardial infarction in patients with established cardiovascular disease. The antithrombotic effect of aspirin is due to inhibition of platelet aggregation by blocking the production of thromboxane A2. Long-term aspirin is recommended in all patients with known cardiovascular disease who do not have relative contraindications, such as a history of gastrointestinal (GI) bleeding or peptic ulcer. The recommended dose in the United States is 81 mg/day. The indications for aspirin in primary prevention—that is in patients with risk factors for cardiovascular disease who do not have a history of coronary heart disease or stroke—are not as clear.
The Physicians’ Health study in 1989 randomized 22,071 physicians without a history of coronary artery disease to 325 mg aspirin every other day or placebo. After 5 years of therapy, they reported a very significant (P < .00001) reduction in myocardial infarction in those in the aspirin arm. However, multiple primary prevention trials since have been negative. As a result, many have concluded that aspirin is not indicated for primary prevention because the potential benefit is exceeded by the risk for GI bleeding. All of the primary prevention trials have used doses of aspirin of 100 mg or less per day; it is possible that a larger dose of aspirin could reduce the incidence of myocardial infarction, as shown with 325 mg every other day in the Physicians’ Health Study.
Aspirin can only prevent stroke and myocardial infarction in patients who have cardiovascular disease. Many of the patients in primary prevention trials did not have cardiovascular disease despite the presence of risk factors. The presence of an unknown number of patients without cardiovascular disease in primary prevention trials would make it difficult to demonstrate a treatment effect of aspirin.
In recommending aspirin therapy for primary prevention, one must weigh the risk for stroke or myocardial infarction against the risk for GI bleeding. Many recommend that the 10-year risk for myocardial infarction by Framingham models should exceed 10% to justify long-term aspirin prophylaxis. The increased risk for a significant GI bleed in patients taking aspirin compared with those not taking aspirin is approximately 0.5 to 1 case per 1000 patients per year. Multiple studies have shown that the incidence of GI bleeds does not increase when the aspirin dose is increased from 81 to 325 mg/day.
I recommend aspirin, 81 mg/day, in patients with established cardiovascular disease who do not have relative contraindications. In patients with multiple risk factors without evidence of cardiovascular disease, I discuss with them the potential prevention of stroke or myocardial infarction with aspirin 162 mg/day vs the risk for a significant GI bleed. After our discussion, the patient makes the final decision.
James E Dalen MD, MPH, ScD (hon)