TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, 350 Longwood Avenue, 1st Floor Offices, Boston, MA 02115, USA.
Duke Clinical Research Institute, Durham, NC, USA.
Eur Heart J. 2016 Dec 21;37(48):3576-3584. doi: 10.1093/eurheartj/ehw377. Epub 2016 Aug 28.
To examine the efficacy and safety of ezetimibe added to statin in patients with prior coronary artery bypass graft surgery (CABG) following hospitalization for an acute coronary syndrome (ACS).
In the IMPROVE-IT trial, post-ACS patients with mean low density lipoprotein cholesterol (LDL-C) of 93.8 mg/dL at presentation were randomized to simvastatin/ezetimibe or simvastatin/placebo. The primary endpoint was cardiovascular death, major coronary event or stroke, and the median follow-up was 6 years. Efficacy and safety endpoints were examined by prior CABG status. Among 18 134 patients, 1684 (9.3%) had a prior CABG (median age 69 years, 82% male). During the trial, the median time-weighted LDL-C level was 55.0 mg/dL with simvastatin/ezetimibe vs. 69.9 mg/dL with simvastatin/placebo in patients with prior CABG (P < 0.001), and it was 53.6 mg/dL vs. 69.5 mg/dL, respectively, in patients without prior CABG (P < 0.001). The rate of the primary endpoint was higher in patients with vs. without prior CABG [56% vs. 32%, adj. hazard ratio 1.45, 95% confidence interval (CI) 1.33-1.58]. Patients with prior CABG receiving simvastatin/ezetimibe had an 8.8% (95% CI 3.1-14.6%) lower absolute risk over simvastatin/placebo in the primary endpoint, whereas patients without prior CABG had a 1.3% (95% CI 0-2.6%) lower absolute risk (P-interaction = 0.02). There were no between-group significant differences in safety endpoints.
The clinical benefit of adding ezetimibe to statin appears to be enhanced in patients with prior CABG, supporting the use of intensive lipid lowering therapy in these high-risk patients following ACS.
研究在因急性冠脉综合征（ACS）住院后行冠状动脉旁路移植术（CABG）的患者中，加用依折麦布联合他汀类药物的疗效和安全性。
在 IMPROVE-IT 试验中，平均 LDL-C 为 93.8mg/dL 的 ACS 患者入院后随机接受辛伐他汀/依折麦布或辛伐他汀/安慰剂治疗。主要终点是心血管死亡、主要冠脉事件或卒中等，中位随访时间为 6 年。通过既往 CABG 状态来检查疗效和安全性终点。在 18134 例患者中，有 1684 例（9.3%）有既往 CABG（中位年龄 69 岁，82%为男性）。在试验期间，与辛伐他汀/安慰剂相比，既往 CABG 患者的中位时间加权 LDL-C 水平分别为辛伐他汀/依折麦布 55.0mg/dL 和 69.9mg/dL（P<0.001），而无既往 CABG 患者的中位时间加权 LDL-C 水平分别为 53.6mg/dL 和 69.5mg/dL（P<0.001）。与无既往 CABG 患者相比，既往 CABG 患者的主要终点发生率更高[56% vs. 32%，校正后的风险比 1.45，95%置信区间（CI）1.33-1.58]。既往 CABG 患者接受辛伐他汀/依折麦布治疗时，在主要终点方面的绝对风险降低 8.8%（95%CI 3.1-14.6%），而无既往 CABG 患者的绝对风险降低 1.3%（95%CI 0-2.6%）（P 交互=0.02）。两组间安全性终点无显著差异。
在既往 CABG 患者中，加用依折麦布联合他汀类药物的临床获益似乎增强，支持 ACS 后高危患者进行强化降脂治疗。
