Hu D Y, Huang D J, Yuan Z Y, Zhao R P, Yan X W, Wang M H
Department of Cardiology, Peking University People's Hospital, Beijing 100044, China.
Zhonghua Xin Xue Guan Bing Za Zhi. 2017 Mar 24;45(3):190-197. doi: 10.3760/cma.j.issn.0253-3758.2017.03.005.
To evaluate the efficacy and safety of ivabradine for the treatment of Chinese patients with chronic heart failure based on the Chinese subgroup data of the systolic heart failure treatment with the (f) inhibitor ivabradine trial (SHIFT). A total of 6 558 stable outpatients who presented symptoms of heart failure, with a left ventricular ejection fraction (LVEF) ≤35%, sinus rhythms with a heart rate ≥70 bpm participated in the randomized, double-blind, placebo-controlled, international multicenter clinical study.The subset of Chinese patients with heart rate ≥75 bpm was enrolled in the post-hoc subgroup analyses.Patients were randomly allocated by computer-generated assignment through a telephone interactive voice response system to ivabradine group (starting dose 5 mg bid, which was then uptitrated to the maximum 7.5 mg bid) or matched placebo group.The clinical baseline characteristics of participants were obtained and analyzed.The primary outcome endpoint was a composite endpoint of cardiovascular death or hospitalization resulting from worsening HF.The primary safety endpoint included total incidence of adverse events during the study, bradycardia, and adverse visual reaction (phosphenes). A total of 49 Chinese centers enrolled a total of 225 patients with chronic heart failure, of whom, 106 patients were randomized to the ivabradine group and the other 119 patients to the placebo group, and the mean follow-up time was (15.6±5.1) months.By the end of the study, mean heart rate (71.0 bpm vs. 80.3 bpm, <0.05) and incidence of the primary endpoint events (18.9% (20/106) vs. 31.9%(38/119), =0.56, 95% 0.33-0.97, =0.039) were significantly lower, while the percentage of patients with improvement in heart functional class NYHA (53.8% (56/106) vs. 34.5% (41/119), =0.006 1) was significantly higher in the ivabradine group than in the placebo group.The total number of adverse events (129 events, 49.6% PY) in the ivabradine group was lower than that in the placebo group (203 events, 50.8% PY). In the ivabradine group and the placebo group, there were respectively 2 patients (1.9%) and 0 patients experienced bradycardia, 3 patients (2.9%) and 1 patient (0.8%) experienced adverse visual reaction (phosphenes). Ivabradine significantly reduced heart rate and improved the clinical outcomes and NYHA function class in Chinese patients with chronic heart failure, these beneficial effects are achieved without inducing remarkable adverse reactions.The results of Chinese subgroup analysis were thus consistent with the overall results of the SHIFT study. International standard randomized controlled trials registry, ISRCTN 70429960.
基于伊伐布雷定治疗收缩性心力衰竭试验（SHIFT）中的中国亚组数据，评估伊伐布雷定治疗中国慢性心力衰竭患者的有效性和安全性。共有6558例有心力衰竭症状、左心室射血分数（LVEF）≤35%、心率≥70次/分的窦性心律的稳定门诊患者参与了这项随机、双盲、安慰剂对照的国际多中心临床研究。心率≥75次/分的中国患者亚组纳入事后亚组分析。患者通过电话交互式语音应答系统由计算机生成的分配方式随机分配至伊伐布雷定组（起始剂量5mg，每日2次，然后滴定至最大7.5mg，每日2次）或匹配的安慰剂组。获取并分析参与者的临床基线特征。主要结局终点是心血管死亡或因心力衰竭恶化导致住院的复合终点。主要安全终点包括研究期间不良事件的总发生率、心动过缓和不良视觉反应（光幻视）。共有49个中国中心纳入了225例慢性心力衰竭患者，其中，106例患者随机分配至伊伐布雷定组，另外119例患者分配至安慰剂组，平均随访时间为（15.6±5.1）个月。到研究结束时，伊伐布雷定组的平均心率（71.0次/分对80.3次/分，P<0.05）和主要终点事件发生率（18.9%（20/106）对31.9%（38/119），P = 0.56，95%CI 0.33 - 0.97，P = 0.039）显著更低，而纽约心脏病协会（NYHA）心功能分级改善的患者百分比（53.8%（56/）对34.5%（41/119），P = 0.0061）显著高于安慰剂组。伊伐布雷定组不良事件总数（129例事件，49.6%人年）低于安慰剂组（203例事件，50.8%人年）。在伊伐布雷定组和安慰剂组中，分别有2例患者（1.9%）和0例患者发生心动过缓，3例患者（2.9%）和1例患者（0.8%）发生不良视觉反应（光幻视）。伊伐布雷定显著降低中国慢性心力衰竭患者的心率，改善临床结局和NYHA心功能分级，且未引起明显不良反应。因此，中国亚组分析结果与SHIFT研究的总体结果一致。国际标准随机对照试验注册库，ISRCTN 70429960。
