CHOLESTEROL-LOWERING WITH STATIN DRUGS, RISK OF STROKE, AND TOTAL MORTALITY - AN OVERVIEW OF RANDOMIZED TRIALS

Objective.-To examine whether cholesterol lowering with 3-hydroxy-3-me thylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statin drugs) reduces the risks of stroke and total mortality. Data Sources.-We cond ucted a computerized literature search from 1985 through 1995 to ident ify all published trials testing statin drugs. The Cholesterol and Rec urrent Events (CARE) data were added after the report was published in October 1996. Our search was limited to English-language articles and included published overviews containing relevant individual trials. T rial Selection.-Criteria for inclusion of randomized trials in the ove rview were (1) statin drugs alone used to reduce lipid levels rather t han multifactorial interventions including another type of cholesterol -lowering drug and (2) inclusion of data on deaths and/or strokes. Dat a Extraction.-Data were extracted by 2 researchers, and only minor dis crepancies, which were easily resolved by discussion, occurred. Princi pal investigators of the trials and their funding agencies were also c ontacted to secure any relevant data not included in the published rep orts. Data Synthesis.-A total of 16 individual trials including approx imately 29 000 subjects treated and followed up an average of 3.3 year s were included in the overview. The average reductions in total and l ow-density lipoprotein cholesterol achieved were large-22% and 30%, re spectively. A total of 454 strokes (fatal plus nonfatal) and 1175 deat hs occurred. Those assigned to statin drugs experienced significant re ductions in risks of stroke of 29% (95% confidence interval [CI], 14%- 41%) as well as total mortality of 22% (95% CI, 12%-31%), which was at tributable to a significant reduction in cardiovascular disease (CVD) deaths of 28% (95% CI, 16%-37%), There was no evidence of any increase d risk in non-CVD mortality (relative risk [RR], 0.93; 95% CI, 0.75-1. 14), There was also no significant increase in risk of cancer (RR, 1.0 3; 95% CI, 0.90-1.17). Conclusion.-This overview of all published rand omized trials of statin drugs demonstrates large reductions in cholest erol and clear evidence of benefit on stroke and total mortality. Ther e was, as expected, a large and significant decrease in CVD mortality, but there was no significant evidence for any increases in either non -CVD deaths or cancer incidence.