Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes.

Abstract

BACKGROUND:

Statin therapy reduces low-density lipoprotein (LDL) cholesterol levels and the risk of cardiovascular events, but whether the addition of ezetimibe, a nonstatin drug that reduces intestinal cholesterol absorption, can reduce the rate of cardiovascular events further is not known.

METHODS:

We conducted a double-blind, randomized trial involving 18,144 patients who had been hospitalized for an acute coronary syndrome within the preceding 10 days and had LDL cholesterol levels of 50 to 100 mg per deciliter (1.3 to 2.6 mmol per liter) if they were receiving lipid-lowering therapy or 50 to 125 mg per deciliter (1.3 to 3.2 mmol per liter) if they were not receiving lipid-lowering therapy. The combination of simvastatin (40 mg) and ezetimibe (10 mg) (simvastatin-ezetimibe) was compared with simvastatin (40 mg) and placebo (simvastatin monotherapy). The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, unstable angina requiring rehospitalization, coronary revascularization (≥30 days after randomization), or nonfatal stroke. The median follow-up was 6 years.

RESULTS:

The median time-weighted average LDL cholesterol level during the study was 53.7 mg per deciliter (1.4 mmol per liter) in the simvastatin-ezetimibe group, as compared with 69.5 mg per deciliter (1.8 mmol per liter) 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, as compared with 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 in the two groups.

CONCLUSIONS:

When added to statin therapy, ezetimibe resulted in incremental lowering of LDL cholesterol levels and improved cardiovascular outcomes. Moreover, lowering LDL cholesterol to levels below previous targets provided additional benefit. (Funded by Merck; IMPROVE-IT ClinicalTrials.gov number, NCT00202878.).

• Authors: Christopher P Cannon, Michael A Blazing, Robert P Giugliano, Amy McCagg, Jennifer A White, Pierre Theroux, Harald Darius, Basil S Lewis, Ton Oude Ophuis, J Wouter Jukema, Gaetano M De Ferrari, Witold Ruzyllo, Paul De Lucca, KyungAh Im, Erin A Bohula, Craig Reist, Stephen D Wiviott, Andrew M Tershakovec, Thomas A Musliner, Eugene Braunwald, Robert M Califf, IMPROVE-IT Investigators
• Journal: The New England journal of medicine (N Engl J Med) Vol. 372 Issue 25 Pg. 2387-97 (Jun 18 2015) ISSN: 1533-4406 [Electronic] United States
• PMID: 26039521 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anticholesteremic Agents
• Azetidines
• Cholesterol, LDL
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Triglycerides
• Simvastatin
• Ezetimibe

Topics

• Acute Coronary Syndrome (drug therapy)
• Aged
• Anticholesteremic Agents (adverse effects, therapeutic use)
• Azetidines (adverse effects, therapeutic use)
• Cardiovascular Diseases (epidemiology, mortality, prevention & control)
• Cholesterol, LDL (blood)
• Double-Blind Method
• Drug Therapy, Combination
• Ezetimibe
• Female
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (adverse effects, therapeutic use)
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Simvastatin (therapeutic use)
• Triglycerides (blood)