On-treatment analysis of the Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT).

Abstract

BACKGROUND:

We aimed to determine the efficacy and safety of adding ezetimibe (Ez) to simvastatin (S) in a post-acute coronary syndrome (ACS) population in a prespecified on-treatment analysis.

METHODS:

We evaluated 17,706 post-ACS patients from the IMPROVE-IT trial who had low-density lipoprotein cholesterol values between 50 and 125 mg/dL and who received Ez 10 mg/d with S 40 mg/d (Ez/S) or placebo with simvastatin 40 mg/d (P/S). The primary composite end point was cardiovascular death, myocardial infarction, unstable angina, coronary revascularization ≥30 days postrandomization, or stroke. The on-treatment analysis included patients who received study drug for the duration of the trial or experienced a primary end point or noncardiovascular death within 30 days of drug discontinuation.

RESULTS:

Mean low-density lipoprotein cholesterol values at 1 year were 71 mg/dL for P/S and 54 mg/dL for Ez/S (absolute difference -17 mg/dL = -24%; P < .001). The 7-year Kaplan-Meier estimate of the primary end point occurred in 32.4% in the P/S arm and 29.8% in the Ez/S arm (absolute difference 2.6%; HRadj 0.92 [95% CI 0.87-0.98]; P = .01). The absolute treatment effect favoring Ez/S was 30% greater than in the intention-to-treat analysis of IMPROVE-IT.

CONCLUSIONS:

This analysis provides additional support for the efficacy and safety of adding Ez to S in this high-risk, post-ACS population.

• Authors: Michael A Blazing, Robert P Giugliano, James A de Lemos, Christopher P Cannon, Andrew Tonkin, Christie M Ballantyne, Basil S Lewis, Thomas A Musliner, Andrew M Tershakovec, Yuliya Lokhnygina, Jennifer A White, Craig Reist, Amy McCagg, Eugene Braunwald
• Journal: American heart journal (Am Heart J) Vol. 182 Pg. 89-96 (Dec 2016) ISSN: 1097-6744 [Electronic] United States
• PMID: 27914504 (Publication Type: Journal Article, Randomized Controlled Trial)
• Copyright: Copyright © 2016 Elsevier Inc. All rights reserved.

Chemical References

• Anticholesteremic Agents
• Cholesterol, LDL
• Simvastatin
• Ezetimibe

Topics

• Acute Coronary Syndrome (blood, diagnosis, drug therapy)
• Aged
• Anticholesteremic Agents (administration & dosage, adverse effects)
• Cholesterol, LDL (blood)
• Dose-Response Relationship, Drug
• Drug Monitoring (methods)
• Drug Synergism
• Drug Therapy, Combination (methods, statistics & numerical data)
• Ezetimibe (administration & dosage, adverse effects)
• Female
• Humans
• Male
• Middle Aged
• Simvastatin (administration & dosage, adverse effects)
• Treatment Outcome