Evaluating cardiovascular event reduction with ezetimibe as an adjunct to simvastatin in 18,144 patients after acute coronary syndromes: final baseline characteristics of the IMPROVE-IT study population.

Abstract

BACKGROUND:

The IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) is evaluating the potential benefit for reduction in major cardiovascular (CV) events from the addition of ezetimibe versus placebo to 40 mg/d of simvastatin therapy in patients who present with acute coronary syndromes and have low-density lipoprotein cholesterol (LDL-C) ≤ 125 mg/dL.

METHODS:

The primary composite end point is CV death, nonfatal myocardial infarction (MI), nonfatal stroke, rehospitalization for unstable angina (UA), and coronary revascularization (≥ 30 days postrandomization). The simvastatin monotherapy arm's LDL-C target is <70 mg/dL. Ezetimibe was assumed to further lower LDL-C by 15 mg/dL and produce an estimated ~8% to 9% treatment effect. The targeted number of events is 5,250.

RESULTS:

We enrolled 18,144 patients with either ST-segment elevation MI (STEMI, n = 5,192) or UA/non-ST-segment elevation MI (UA/NSTEMI, n = 12,952) from October 2005 to July 2010. Western Europe (40%) and North America (38%) were the leading enrolling regions. The STEMI cohort was younger and had a higher percentage of patients naive to lipid-lowering treatment compared with the UA/NSTEMI cohort. The UA/NSTEMI group had a higher prevalence of diabetes, hypertension, and prior MI. Median LDL-C at entry was 100 mg/dL for STEMI and 93 mg/dL for UA/NSTEMI patients.

CONCLUSIONS:

This trial is evaluating LDL-C lowering beyond previously targeted LDL-C levels. The results depend on achieving the desired separation of LDL-C with ezetimibe and on the assumption that ezetimibe's lowering of LDL-C will have similar event reduction efficacy as the LDL-C lowering from a statin. The results could affect future therapies and guidelines.

• Authors: Michael A Blazing, Robert P Giugliano, Christopher P Cannon, Thomas A Musliner, Andrew M Tershakovec, Jennifer A White, Craig Reist, Amy McCagg, Eugene Braunwald, Robert M Califf
• Journal: American heart journal (Am Heart J) Vol. 168 Issue 2 Pg. 205-12.e1 (Aug 2014) ISSN: 1097-6744 [Electronic] United States
• PMID: 25066560 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 The Authors. Published by Mosby, Inc. All rights reserved.

Chemical References

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

Topics

• Acute Coronary Syndrome (blood, complications, drug therapy)
• Aged
• Anticholesteremic Agents (pharmacology, therapeutic use)
• Azetidines (pharmacology, therapeutic use)
• Cardiovascular Diseases (drug therapy, epidemiology, prevention & control)
• Cholesterol, LDL (blood, drug effects)
• Drug Therapy, Combination
• Ezetimibe
• Female
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (pharmacology, therapeutic use)
• Male
• Middle Aged
• Simvastatin (therapeutic use)