Reduction of stroke incidence after myocardial infarction with pravastatin- The cholesterol and recurrent events (CARE) study

Background-The role of lipid modification in stroke prevention is controver sial, although increasing evidence suggests that HMG-CoA reductase inhibiti on may reduce cerebrovascular events in patients with prevalent coronary ar tery disease. Methods and Results-To test the hypothesis that cholesterol reduction with pravastatin may reduce stroke incidence after myocardial infarction, we fol lowed 4159 subjects with average total and LDL serum cholesterol levels (me an, 209 and 139 mg/dL, respectively) who had sustained an infarction an ave rage of 10 months before study entry and who were randomized to pravastatin 40 mg/d or placebo in the Cholesterol and Recurrent Events (CARE) trial. U sing prospectively defined criteria, we assessed the incidence of stroke, a prespecified secondary end point, and transient ischemic attack (TIA) over a median 5-year follow-up period. Patients were well matched for stroke ri sk factors and the use of antiplatelet agents (85% of subjects in each grou p). Compared with placebo, pravastatin lowered total serum cholesterol by 2 0%, LDL cholesterol by 32%, and triglycerides by 14% and raised HDL cholest erol by 5% over the course of the trial. A total of 128 strokes (52 on prav astatin, 76 on placebo) and 216 strokes or TIAs (92 on pravastatin, 124 on placebo) were observed, representing a 32% reduction (95% CI, 4% to 52%, P= 0.03) in all-cause stroke and 27% reduction in stroke or TIA (95% CI, 4% to 44%, P=0.02). All categories of strokes were reduced, and treatment effect was similar when adjusted for age, sex, history of hypertension, cigarette smoking, diabetes, left ventricular ejection fraction, and baseline total, HDL, and LDL cholesterol and triglyceride levels. There was no increase in hemorrhagic stroke in patients on pravastatin compared with placebo (2 ver sus 6, respectively). Conclusions-Pravastatin significantly reduced stroke and stroke or TIA inci dence after myocardial infarction in patients with average serum cholestero l levels despite the high concurrent use of antiplatelet therapy.