Low-dose aspirin therapy for chronic stable angina. A randomized, placebo-controlled clinical trial

OBJECTIVE: To evaluate the efficacy of low-dose aspirin in the primary prevention of myocardial infarction among patients with chronic stable angina. DESIGN: A randomized, double-blind, trial. PATIENTS: The study included 333 men with baseline chronic stable angina but with no previous history of myocardial infarction, stroke, or transient ischemic attack who were enrolled in the Physicians' Health Study, a trial of aspirin among 22,071 male physicians. INTERVENTION: Patients were randomly assigned to receive alternate-day aspirin therapy (325 mg) or placebo and were followed for an average of 60.2 months for the occurrence of myocardial infarction, stroke, or cardiovascular death. RESULTS: During follow-up, 27 patients had confirmed myocardial infarctions; 7 were among the 178 patients with chronic stable angina who received aspirin therapy and 20 were among the 155 patients who received placebo (relative risk, 0.30; 95% CI, 0.14 to 0.63; P = 0.003). While simultaneously controlling for other cardiovascular risk factors in a proportional hazards model, an overall 87% risk reduction was calculated (relative risk, 0.13; CI, 0.04 to 0.42; P less than 0.001). For the subgroup of patients with chronic stable angina but no previous coronary bypass surgery or coronary angioplasty, an almost identical reduction in the risk for myocardial infarction was found (relative risk, 0.14; CI, 0.04 to 0.56; P = 0.006). Of 13 strokes, 11 occurred in the aspirin group and 2 in the placebo group (relative risk, 5.4; CI, 1.3 to 22.1; P = 0.02). No stroke was fatal, but 4 produced some long-term impairment of function. One stroke, in the aspirin group, was hemorrhagic. CONCLUSION: Our data indicated that alternate-day aspirin therapy greatly reduced the risk for first myocardial infarction among patients with chronic stable angina, a group of patients at high risk for cardiovascular death (P less than 0.001). Although our results for stroke were based on small numbers, they suggested an apparent increase in frequency of stroke with aspirin therapy; this finding requires confirmation in randomized trials of adequate sample size.