Ezetimibe with Simvastatin Reduced Total Cardiovascular Events

IMPROVE-IT trial results support the continuation of combination lipid-lowering therapy after a cardiovascular event.

Lipoprotein therapy with ezetimibe plus simvastatin doubled the number of prevented total cardiovascular events when compared with the number of first events, according to results from the IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial) trial.

IMPROVE-IT investigators tested the effects of combination lipoprotein cholesterol therapy on post-acute coronary syndrome (ACS) patients to determine the rate of prevented first cardiovascular events over a 6-year median follow-up period.

The trial results “demonstrated that the addition of the nonstatin lipid-lowering agent ezetimibe when added to simvastatin reduced LDL-C by approximately an additional 24% and resulted in a significantly lower risk of first cardiovascular events compared with statin monotherapy,” the authors wrote in their study, published in the Journal of the American College of Cardiology.

“The present study extends these findings, demonstrating a reduction not only in first events but in total events over long-term follow-up with the addition of ezetimibe to statin therapy.”

The IMPROVE-IT trial included 18 144 patients randomly assigned to receive ezetimibe and simvastatin therapy or a placebo and simvastatin therapy. Researchers observed all cardiovascular events including cardiovascular death, myocardial infarction, stroke, unstable angina, and coronary revascularization.

A total of 9545 total CV cardiovascular events occurred—56% were first events and 44% were subsequent events. The total number of CV events was reduced by 9% with ezetimibe and simvastatin compared to the placebo group (incidence-rate ratio [RR]: 0.91; 95% confidence interval [CI]: 0.85- 0.97; P=.007).

In addition, both secondary composite end points (all death/MI/coronary revascularization/stroke) and exploratory end points (CV death, MI, and stroke) were also reduced in the ezetimibe and simvastatin group compared with placebo (secondary RR: 0.92; 95% CI: 0.81-0.96; P=.002 and exploratory RR: 0.88; 95% CI: 0.81- 0.96; P=.002).

Researchers also noted that the decrease in total CV events was driven by decreases in total nonfatal MI (RR: 0.87; 95% CI: 0.79- 0.96; P=.004) and total nonfatal stroke (RR: 0.77; 95% CI: 0.65- 0.93; P=.005).

“These data provide further support for the benefit of continuation of intensive combination lipid-lowering therapy after a recurrent cardiovascular event,” the authors concluded.

The authors suggest that further research should be conducted to compare the effects of other intensive lipid-lowering strategies on total cardiovascular events during long-term therapy in high-risk patient populations.


Murphy SA, Cannon CP, Blazing MA, et al. Reduction in total cardiovascular events with ezetimibe/simvastatin post-acute coronary syndrome: The IMPROVE-IT trial. J Am Coll Cardiol. 2016; 67(4):353-61. doi: 10.1016/j.jacc.2015.10.077.