辛伐他汀/依折麦布联合用药对主动脉瓣膜狭窄的患者强化降脂的研究

摘要：高脂血症是主动脉瓣狭窄的诱因，但是关于降脂的研究仍然存在很多问题，需要进一步的研究。对主动脉瓣膜狭窄的患者，采用辛伐他汀/依折麦布联合用药，对其降脂效果进行研究。结论： 研究结果提示采用辛伐他汀/依折麦布联合用药虽未能明显减少主动脉瓣狭窄和缺血性事件的发生率，但降低了缺血性心血管事件的发生率。

Background  Hyperlipidemia has been suggested as a risk factor for stenosis of the aortic valve, but lipid-lowering studies have had conflicting results.

Methods  We conducted a randomized, double-blind trial involving 1873 patients with mild tomoderate, asymptomatic  aortic stenosis. The patients received either 40 mg of simvastatinplus 10 mg of ezetimibe or placebo daily. The primary outcome was a composite of major cardiovascular events, including death from cardiovascular causes,aortic-valve replacement, nonfatal myocardial infarction, hospitalization for unstable angina pectoris, heart failure, coronary-artery bypass grafting, percutaneous coronary intervention, and nonhemorrhagic stroke. Secondary outcomes were events related to aortic-valve stenosis and ischemic cardiovascular events.

Results  During a median follow-up of 52.2 months, the primary outcome occurred in 333 patients (35.3%) in the simvastatin–ezetimibe group and in 355 patients (38.2%) in theplacebo group (hazard ratio in the simvastatin–ezetimibe group, 0.96; 95% confidence interval [CI], 0.83 to 1.12; P = 0.59). Aortic-valve replacement was performed in 267 patients (28.3%) in the simvastatin–ezetimibe group and in 278 patients (29.9%)in the placebo group (hazard ratio, 1.00; 95% CI, 0.84 to 1.18; P = 0.97). Fewer patients had ischemic cardiovascular events in the simvastatin–ezetimibe group (148 patients) than in the placebo group (187 patients) (hazard ratio, 0.78; 95% CI, 0.63 to 0.97; P = 0.02), mainly because of the smaller number of patients who underwent coronary-artery bypass grafting. Cancer occurred more frequently in the simvastatin–ezetimibe group (105 vs. 70, P = 0.01).

Conclusions  Simvastatin and ezetimibe did not reduce the composite outcome of combined aorticvalve events and ischemic events in patients with aortic stenosis. Such therapy reduced the incidence of ischemic cardiovascular events but not events related to aortic-valve stenosis.