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.


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“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.

Reference

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.