[改善转归：Vytorin疗效国际试验（IMPROVE-IT研究）]

[IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (studie IMPROVE-IT)].

作者信息

Špinar Jindřich, Špinarová Lenka, Vítovec Jiří

出版信息

Vnitr Lek. 2014 Dec;60(12):1095-101.

Abstract

BACKGROUND

The IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) is evaluating the potential benefit for reduction in major cardiovascular (CV) events from the addition of ezetimibe versus placebo to 40 mg/d of simvastatin therapy in patients who present with acute coronary syndromes and have low-density lipoprotein cholesterol (LDL-C) 125 mg/dl.

METHODS

Randomized double blind clinical trial in patients with acute coronary syndrome and low cholesterol level. The simvastatin monotherapy arms LDL-C target was < 70 mg/dl, the comparison arm was simvastatin + ezetimibe. Ezetimibe was assumed to further lower LDL-C by 15 mg/dl and produce an estimated ~ 8 % to 9 % treatment effect. The primary composite end point was CV death, nonfatal myocardial infarction (MI), nonfatal stroke, rehospitalization for unstable angina (UA), and coronary revascularization ( 30 days postrandomization). The targeted number of events was 5,250.

RESULTS

18,144 patients were enroled with either ST segment elevation MI (STEMI, n = 5,192) or UA/non-ST segment elevation MI (UA/NSTEMI, n = 12,952) from October 2005 to July 2010. Primary endpoint occured in 2 742 patients (34.7 %) treated with simvastatin in monotherapy and in 2 572 patients (32.7 %) (p = 0.016) treated with combination. Compared to patients with coronary heart disease given the drug simvastatin plus a placebo, those given both simvastatin and the non-statin drug, ezetimibe, had a 6.4 % lower combined risk of subsequent heart attack, stroke, cardiovascular death, rehospitalization for unstable angina and procedures to restore blood flow to the heart. Heart attacks alone were reduced by 13 %, and non-fatal stroke by 20 %. Deaths from cardiovascular disease were statistically the same in both groups. Patients were followed an average of approximately six years, and some as long as 8.5 years. Approximately 2 patients out of every 100 patients treated for 7 years avoided a heart attack or stroke [Number Needed to Treat (NNT) = 50/7 years].

CONCLUSIONS

The study has shown a claer benefit from combination treatment with simvastatin and ezetimibe in patients with acute coronary syndrome and low LDL-C.

摘要

背景

改善转归：Vytorin疗效国际试验（IMPROVE-IT）正在评估，对于急性冠状动脉综合征患者且低密度脂蛋白胆固醇（LDL-C）≥125mg/dl，在辛伐他汀40mg/d治疗基础上加用依折麦布对比安慰剂，在降低主要心血管（CV）事件方面的潜在益处。

方法

对急性冠状动脉综合征且胆固醇水平较低的患者进行随机双盲临床试验。辛伐他汀单药治疗组的LDL-C目标为<70mg/dl，对比组为辛伐他汀+依折麦布。假设依折麦布可使LDL-C进一步降低15mg/dl，并产生约8%至9%的治疗效果。主要复合终点为CV死亡、非致死性心肌梗死（MI）、非致死性卒中、因不稳定型心绞痛（UA）再次住院以及冠状动脉血运重建（随机分组后30天内）。目标事件数为5250例。

结果

2005年10月至2010年7月，共纳入18144例ST段抬高型心肌梗死（STEMI，n=5192）或UA/非ST段抬高型心肌梗死（UA/NSTEMI，n=12952）患者。辛伐他汀单药治疗的2742例患者（34.7%）以及联合治疗的2572例患者（32.7%）出现了主要终点（p=0.016）。与给予辛伐他汀加安慰剂的冠心病患者相比，给予辛伐他汀和非他汀类药物依折麦布的患者，后续心脏病发作、卒中、心血管死亡、因不稳定型心绞痛再次住院以及心脏血流恢复手术的联合风险降低了6.4%。仅心脏病发作减少了13%，非致死性卒中减少了20%。两组心血管疾病死亡在统计学上无差异。患者平均随访约6年，部分长达8.5年。每100例接受7年治疗的患者中约有2例避免了心脏病发作或卒中[需治疗人数（NNT）=50/7年]。