A new study suggests the addition of ezetimibe to simvastatin may improve cardiovascular outcomes in patients with acute coronary syndrome (ACS), although the effect is modest.

More than 18,000 patients who had been hospitalized for ACS and had low-density lipoprotein (LDL) cholesterol levels < 100 mg/dL (if they were on lipid-lowering therapy) or LDL 50-125 mg/dL (if they were not on lipid-lowering therapy) were randomized to simvastatin 40 mg plus ezetimibe 10 mg or simvastatin 40 mg plus placebo.

The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, unstable angina requiring hospitalization, coronary revascularization, or nonfatal stroke. The median follow up was 6 years. The combination resulted in lower LDL cholesterol levels (53.7 mg/dL for the combination vs 69.5 mg/dL for simvastatin alone, P < 0.001). The Kaplan-Meier event rate for the primary endpoint at 7 years was 32.7% for the combination and 34.7% for simvastatin alone (absolute risk difference, 2%; hazard ratio [HR] 0.936; 95% confidence interval [CI], 0.89-0.99; P = 0.016). Adverse effects were similar in both groups. The authors conclude that the addition of ezetimibe to statin therapy resulted in lower LDL levels and improved cardiovascular outcomes (N Eng J Med published online June 3, 2015, doi:10.1056/NEJMoa1410489).

This study has generated considerable controversy, even prompting an accompanying editorial that suggests LDL-lowering goals should be examined again based on this study. Cholesterol treatment guidelines published in 2013 abandoned the “treat to target” method of cardiovascular risk control, instead focusing on the level of risk and emphasizing statin therapy as the preferred treatment option for patients with established cardiovascular disease or hyperlipidemia. The editorialist suggests that this study “offers important new evidence in favor of the LDL hypothesis” and of the efficacy of lowering LDL by any means possible (N Engl J Med published online June 3, 2015. doi:10.1056/NEJMe1507041).

Others argue that the dose of statin used in this study was low by current guidelines, and the incremental effect of ezetimibe was small.