Efficacy of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors forprevention of stroke

OBJECTIVE: To determine if 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are effective in preventing fatal and nonfat al strokes in patients at increased risk of coronary artery disease. DESIGN: Mete-analysis of randomized controlled trials. Clinical trials were identified by a computerized search of MEDLINE (1983 to June 1996), by an assessment of the bibliographies of published studies, mete-analyses and re views, and by contacting pharmaceutical companies that manufacture statins. Trials were included in the analysis if their patients were randomly alloc ated to a statin or placebo group, and reported data on stroke events. Thir teen of 28 clinical trials were selected for review. Data were extracted fo r details of study design, patient characteristics, interventions, duration of therapy, cholesterol measurements, and the number of fatal and nonfatal stroke events in each arm of therapy. Missing data on stroke events were o btained by contacting the investigators of the clinical trials. MAIN RESULTS: Among 19,921 randomized patients, the late of total stroke in the placebo group was 2.38% (90% nonfatal and 10% fatal). In contrast, pat ients who received statins had a 1.67% stroke rate. Using an exact stratifi ed analysis, the pooled odds ratio (OR) for total stroke was 0.70 (95% conf idence interval [CI] 0.57, 0.86; p = .0005). The pooled OR for nonfatal str oke was 0.64 (95% CI 0.51, 0.79; p = .00001), and the pooled OR for fatal s troke was 1.25 (95% CI 0.71, 2.24; p = .4973). In separate analyses, reduct ions in total and nonfatal stroke risk were found to be significant only fo r trials of secondary coronary disease prevention. Regression analysis show ed no statistical association between the magnitude of cholesterol reductio n and the relative risk for any stroke outcome. CONCLUSIONS:The available evidence clearly shows that HMG-CoA reductase inh ibitors reduce the morbidity associated with strokes in patients at increas ed risk of cardiac events. Data from 13 placebo-controlled trials suggest t hat on average one stroke is prevented for every 143 patients treated with statins over a 4-year period.