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 (LDL-C) values between 50 and 125 mg/dL and who received Ez 10 mg/day with S 40 mg/day (Ez/S) or placebo with simvastatin 40 mg/day (P/S). The primary composite endpoint was cardiovascular death, myocardial infarction, unstable angina, coronary revascularization ≥30 days post randomization, or stroke. The on-treatment analysis included patients who received study drug for the duration of the trial or experienced a primary endpoint or non-cardiovascular death within 30 days of drug discontinuation. Results Mean LDL-C 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 endpoint 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.