Reduction in Total Cardiovascular Events With Ezetimibe/Simvastatin Post-Acute Coronary Syndrome: The IMPROVE-IT Trial

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• 作者：Sabina A. Murphy ; MPH^a ; ^{smurphy15@partners.org" class="auth_mail" title="E-mail the corresponding author} ; Christopher P. Cannon ; MD^a ; Michael A. Blazing ; MD^b ; Robert P. Giugliano ; MD^a ; Jennifer A. White ; MS^b ; Yuliya Lokhnygina ; PhD^b ; Craig Reist ; PhD^b ; KyungAh Im ; PhD^a ; Erin A. Bohula ; MD ; DPhil^a ; Daniel Isaza ; MD^c ; Jose Lopez-Sendon ; MD^d ; Mikael Dellborg ; MD^e ; Uma Kher ; PhD^f ; Andrew M. Tershakovec ; MD ; MPH^f ; Eugene Braunwald ; MD^a
• 关键词：ezetimibe ; low-density lipoprotein cholesterol ; simvastatin ; total events
• 刊名：Journal of the American College of Cardiology
• 出版年：2016
• 出版时间：2 February 2016
• 年：2016
• 卷：67
• 期：4
• 页码：353-361
• 全文大小：586 K

文摘

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.

Objectives

This analysis tested the hypothesis that total events, including those beyond the first event, would also be reduced with ezetimibe/simvastatin therapy.

Methods

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.

Results

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).

Conclusions

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)