Reduction in Total Cardiovascular Events With Ezetimibe/Simvastatin Post-Acute Coronary Syndrome

• Published in: Journal of the American College of Cardiology Vol. 67; no. 4; pp. 353 - 361
• Main Authors: Murphy, Sabina A., Cannon, Christopher P., Blazing, Michael A., Giugliano, Robert P., White, Jennifer A., Lokhnygina, Yuliya, Reist, Craig, Im, KyungAh, Bohula, Erin A., Isaza, Daniel, Lopez-Sendon, Jose, Dellborg, Mikael, Kher, Uma, Tershakovec, Andrew M., Braunwald, Eugene
• Format: Journal Article
• Language: English
• Published: New York Elsevier Inc 02.02.2016; Elsevier Limited
• Subjects: Acute coronary syndromes; Body mass index; Cardiology; Cardiovascular; Cardiovascular disease; Cholesterol; Confidence intervals; Coronary vessels; Diabetes; ezetimibe; Heart attacks; Hypertension; Lipids; low-density lipoprotein cholesterol; Sensitivity analysis; simvastatin; Statins; Survival analysis; total events; Variables; WLW; LDL-C; low-density lipoprotein cholesterol; simvastatin; PWP; UA; ACS; CV; ezetimibe; PCI; PEP; total events; MI; Prentice, Williams, and Peterson; Wei, Lin, and Weissfeld; myocardial infarction; primary endpoint; cardiovascular; percutaneous coronary intervention; acute coronary syndrome; unstable angina
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/j.jacc.2015.10.077

Intensive low-density lipoprotein cholesterol therapy with ezetimibe/simvastatin in IMPROVE-IT (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial) significantly reduced the first primary endpoint (PEP) in patients post-acute coronary syndrome (ACS) compared to placebo/simvastatin. This analysis tested the hypothesis that total events, including those beyond the first event, would also be reduced with ezetimibe/simvastatin therapy. All PEP events (cardiovascular [CV] death, myocardial infarction [MI], stroke, unstable angina [UA] leading to hospitalization, coronary revascularization ≥30 days post-randomization) during a median 6-year follow-up were analyzed in patients randomized to receive ezetimibe/simvastatin or placebo/simvastatin in IMPROVE-IT. Negative binomial regression was used for the primary analysis. Among 18,144 patients, there were 9,545 total PEP events (56% were first events and 44% subsequent events). Total PEP events were significantly reduced by 9% with ezetimibe/simvastatin vs placebo/simvastatin (incidence-rate ratio [RR]: 0.91; 95% confidence interval [CI]: 0.85 to 0.97; p = 0.007), as were the 3 pre-specified secondary composite endpoints and the exploratory composite endpoint of CV death, MI, or stroke (RR: 0.88; 95% CI: 0.81 to 0.96; p = 0.002). The reduction in total events was driven by decreases in total nonfatal MI (RR: 0.87; 95% CI: 0.79 to 0.96; p = 0.004) and total NF stroke (RR: 0.77; 95% CI: 0.65 to 0.93; p = 0.005). Lipid-lowering therapy with ezetimibe plus simvastatin improved clinical outcomes. Reductions in total PEP events, driven by reductions in MI and stroke, more than doubled the number of events prevented compared with examining only the first event. These data support continuation of intensive combination lipid-lowering therapy after an initial CV event. (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial [IMPROVE-IT]; NCT00202878)