Results:

A total of 4,650 patients were assigned to receive simvastatin plus ezetimibe and 4,620 to receive placebo. Allocation to simvastatin plus ezetimibe yielded an average low-density lipoprotein (LDL) cholesterol difference of 0.85 mmol/L (standard error, 0.02; with about two-thirds compliance) during a median follow-up of 4.9 years, and produced a 17% proportional reduction in major atherosclerotic events (526 [11.3%] simvastatin plus ezetimibe vs. 619 [13.4%] placebo; rate ratio [RR], 0.83; 95% CI, 0.74-0.94; log-rank p = 0.0021). Nonsignificantly fewer patients allocated to simvastatin plus ezetimibe had a nonfatal myocardial infarction or died from coronary heart disease (213 [4.6%] vs. 230 [5.0%]; RR, 0.92; 95% CI, 0.76-1.11; p = 0.37) and there were significant reductions in nonhemorrhagic stroke (131 [2.8%] vs. 174 [3.8%]; RR, 0.75; 95% CI, 0.60-0.94; p = 0.01) and arterial revascularization procedures (284 [6.1%] vs. 352 [7.6%]; RR, 0.79; 95% CI, 0.68-0.93; p = 0.0036). After weighting for subgroup-specific reductions in LDL cholesterol, there was no good evidence that the proportional effects on major atherosclerotic events differed from the summary RR in any subgroup examined, and, in particular, they were similar in patients on dialysis and those who were not. The excess risk of myopathy was only 2 per 10,000 patients per year of treatment with this combination (9 [0.2%] vs. 5 [0.1%]). There was no evidence of excess risks of hepatitis (21 [0.5%] vs. 18 [0.4%]), gallstones (106 [2.3%] vs. 106 [2.3%]), or cancer (438 [9.4%] vs. 439 [9.5%], p = 0.89) and there was no significant excess of death from any nonvascular cause (668 [14.4%] vs. 612 [13.2%], p = 0.13).