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

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 J Reist, Amy McCagg, Eugene Braunwald

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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.

Original languageEnglish
Pages (from-to)89-96
Number of pages8
JournalAmerican Heart Journal
Volume182
DOIs
Publication statusPublished - 1 Dec 2016

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