Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes.
Level 2 - randomized trial
Individual randomized controlled trial
PubMed 26039521 · doi:10.1056/NEJMoa1410489
What was done
A double-blind, randomized trial evaluated 18,144 patients hospitalized for an acute coronary syndrome within the preceding 10 days with LDL cholesterol levels of 50 to 100 mg/dL (if receiving lipid-lowering therapy) or 50 to 125 mg/dL (if not receiving lipid-lowering therapy). Participants 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 rehospitalization, coronary revascularization (30 or more days after randomization), or nonfatal stroke over a median follow-up of 6 years.
What was found
The median time-weighted average LDL cholesterol level during the study was 53.7 mg/dL in the simvastatin-ezetimibe group versus 69.5 mg/dL in the simvastatin monotherapy group (P < 0.001). The Kaplan-Meier event rate for the primary end point at 7 years was 32.7% in the simvastatin-ezetimibe group versus 34.7% in the simvastatin monotherapy group (absolute risk difference: 2.0 percentage points; hazard ratio: 0.936; 95% confidence interval: 0.89 to 0.99; P = 0.016). Rates of prespecified muscle, gallbladder, and hepatic adverse effects and cancer were similar between groups.
Why it matters
This trial showed that nonstatin LDL lowering with ezetimibe provides incremental clinical benefit when added to statin therapy in post-ACS patients. It demonstrated that lowering LDL cholesterol below prior targets yields additional cardiovascular event reduction.
Limits
The absolute risk reduction was modest (2.0 percentage points over 7 years). The study evaluated simvastatin 40 mg rather than comparing ezetimibe addition directly against high-intensity statin monotherapy, and the population was restricted to post-ACS patients with baseline LDL levels up to 125 mg/dL. The study was funded by industry.
Cited by
- supports Combining a statin with Zetia (ezetimibe) has been shown to be very effective at lowering cholesterol.