Although the importance of the cholesterol level has been established in the prevention of coronary artery disesase, it is less certain whether cholesterol reduction helps prevent strokes. The Cholesterol and Recurrent Events (CARE) trial was a secondary prevention trial designed to see if, after an acute myocardial infarction, HMG-CoA reductase inhibitors could reduce the incidence of fatal and nonfatal coronary events or strokes. Plehn and colleagues performed a review of the cerebrovascular events in the CARE study to determine if pravastatin lowered the patient's chances of a stroke in addition to reducing chances of myocardial infarction.
The study population included 4,159 patients, most of them men, between 21 and 75 years of age who had suffered a myocardial infarction in the previous three to 20 months. Patients were included in the study if they had a total cholesterol level of 240 mg per dL (2.4 g per L) or less, a low-density lipoprotein (LDL) level between 115 and 174 mg per dL (2.95 and 4.50 mmol per L) and fasting triglyceride levels of 350 mg per dL or less. Also enrolled were patients who had a fasting blood glucose level of 220 mg per dL (12.2 mmol per L) or less and a left ventricular ejection fraction of 25 percent or more, with absence of symptomatic congestive heart failure. Patients were randomized to receive either pravastatin, in a dosage of 40 mg per day, or placebo. Eighty-three percent of study participants were taking aspirin; 2 percent were taking other platelet inhibitors. About 3 percent of patients were taking warfarin. A small percentage of patients had a history of previous stroke or transient ischemic attack.
Patients in the pravastatin group experienced a 20 percent decrease in total cholesterol levels, a 32 percent decrease in LDL cholesterol levels and a 5 percent increase in high-density cholesterol levels. All patients were followed for a median of five years. During that time, 76 patients in the placebo group had a first stroke, compared with only 52 patients in the pravastatin group. This represents a 32 percent relative risk reduction (4 to 52 percent; P = 0.03). Likewise, 124 patients in the placebo group had either a transient ischemic attack or a stroke, compared with 92 patients in the pravastatin group, resulting in a relative risk reduction of 27 percent (4 to 44 percent; P = 0.02). The results held up when controlled for age, sex, hypertension, smoking, diabetes, ejection fraction, history of cerebrovascular event and baseline lipid values. The divergence of the treatment arms became apparent about three and one-half years into the study. Patients with higher baseline LDL cholesterol levels had a greater risk reduction. However, this trend did not reach the level of statistical significance.
The authors conclude that further studies should be performed to see if similar results can be achieved in other at-risk populations.
editor's note: The number needed to treat for this study represents the number of patients with recent myocardial infarction who would need to be treated with pravastatin, in a dosage of 40 mg per day, to prevent one stroke or transient ischemic attack over approximately five years. In this study, the number needed to treat is 64.5 patients.—c.c.k.