依泽替米贝联合他汀类药物治疗在女性和男性中的疗效和安全性：来自 IMPROVE-IT（改善结局：ezetimibe 疗效国际试验）的观察。

Efficacy and Safety of Adding Ezetimibe to Statin Therapy Among Women and Men: Insight From IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial).

机构信息

Kyoto University Hospital, Kyoto, Japan.

TIMI (Thrombolysis in Myocardial Infarction) Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.

出版信息

J Am Heart Assoc. 2017 Nov 18;6(11):e006901. doi: 10.1161/JAHA.117.006901.

DOI:10.1161/JAHA.117.006901

PMID:29151034

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5721774/

Abstract

BACKGROUND

IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial) showed that adding the nonstatin ezetimibe to statin therapy further reduced cardiovascular events in patients after an acute coronary syndrome. In a prespecified analysis, we explore results stratified by sex.

METHODS AND RESULTS

In IMPROVE-IT, patients with acute coronary syndrome and low-density lipoprotein cholesterol of 50 to 125 mg/dL were randomized to placebo/simvastatin 40 mg or ezetimibe/simvastatin 10/40 mg. They were followed up for a median of 6 years for the primary composite of cardiovascular death, myocardial infarction, hospitalization for unstable angina, coronary revascularization ≥30 days, and stroke. Among 18 144 patients in IMPROVE-IT, 4416 (24%) were women. At 12 months, the addition of ezetimibe to simvastatin significantly reduced low-density lipoprotein cholesterol from baseline compared with simvastatin monotherapy in men and women equally (absolute reduction, 16.7 mg/dL in men and 16.4 mg/dL in women). Women receiving ezetimibe/simvastatin had a 12% risk reduction over those receiving placebo/simvastatin for the primary composite end point (hazard ratio, 0.88; 95% confidence interval, 0.79-0.99) compared with a 5% reduction for men (hazard ratio, 0.95; 95% confidence interval, 0.90-1.01; =0.26 for interaction). When the total number of primary events was considered, women had an 18% reduction with the addition of ezetimibe (relative risk, 95% confidence interval, 0.81; 0.71-0.94) and men had a 6% reduction (relative risk, 0.94; 95% confidence interval, 0.87-1.02; =0.08 for interaction). The addition of ezetimibe did not increase the rates of safety events in either women or men.

CONCLUSIONS

IMPROVE-IT demonstrated that the benefit of adding ezetimibe to statin is present in both women and men, with a good safety profile supporting the use of intensive, combination, lipid-lowering therapy to optimize cardiovascular outcomes.

CLINICAL TRIAL REGISTRATION

URL: http://www.clinicaltrials.gov. Unique identifier: NCT00202878.

摘要

背景

IMPROVE-IT（改善降脂效果：依折麦布疗效国际试验）表明，在急性冠脉综合征患者中，在他汀类药物治疗的基础上加用非他汀类药物依折麦布可进一步降低心血管事件。在一项预设分析中，我们按性别对结果进行分层分析。

方法和结果

在 IMPROVE-IT 中，随机将急性冠脉综合征且低密度脂蛋白胆固醇（LDL-C）水平在 50 至 125mg/dL 的患者分配至安慰剂/辛伐他汀 40mg 或依折麦布/辛伐他汀 10/40mg 组。中位随访 6 年，主要复合终点为心血管死亡、心肌梗死、不稳定型心绞痛住院、30 天后冠状动脉血运重建和卒中。在 IMPROVE-IT 的 18144 例患者中，4416 例（24%）为女性。在 12 个月时，依折麦布联合辛伐他汀与辛伐他汀单药治疗相比，可同等程度地降低男性和女性的 LDL-C（绝对降幅，男性为 16.7mg/dL，女性为 16.4mg/dL）。与接受安慰剂/辛伐他汀治疗的患者相比，接受依折麦布/辛伐他汀治疗的女性发生主要复合终点事件的风险降低 12%（风险比，0.88；95%置信区间，0.79-0.99），而男性降低 5%（风险比，0.95；95%置信区间，0.90-1.01；=0.26，交互作用检验）。当考虑主要事件的总数时，女性加用依折麦布可降低 18%的风险（相对风险，95%置信区间，0.81；0.71-0.94），而男性降低 6%（相对风险，0.94；95%置信区间，0.87-1.02；=0.08，交互作用检验）。加用依折麦布并未增加女性或男性的安全性事件发生率。