Shiga Tsuyoshi, Suzuki Tsuyoshi, Kida Keisuke, Suzuki Atsushi, Kohno Takashi, Ushijima Akiko, Kiuchi Shunsuke, Ishii Shunsuke, Murata Makoto, Ijichi Takeshi, Suzuki Makoto, Nishikawa Masako
Department of Clinical Pharmacology and Therapeutics, The Jikei University School of Medicine Tokyo Japan.
Department of Cardiology, Tokyo Women's Medical University Tokyo Japan.
Circ Rep. 2023 Mar 24;5(4):157-161. doi: 10.1253/circrep.CR-22-0134. eCollection 2023 Apr 10.
A high resting heart rate is an independent risk factor for mortality and morbidity in patients with cardiovascular diseases. Ivabradine selectively inhibits the funny current ( ) and decreases heart rate without affecting cardiac conduction, contractility, or blood pressure. The effect of ivabradine on exercise tolerance in patients with heart failure with reduced ejection fraction (HFrEF) on standard drug therapies remains unclear. This multicenter interventional trial of patients with HFrEF and a resting heart rate ≥75 beats/min in sinus rhythm treated with standard drug therapies will consist of 2 periods: a 12-week open-label, randomized, parallel-group intervention period (standard drug treatment+ivabradine group and standard drug treatment group) to compare changes in exercise tolerance between the 2 groups; and a 12-week open-label ivabradine treatment period for all patients to evaluate the effect of adding ivabradine on exercise tolerance. The primary endpoint will be the change in peak oxygen uptake (V̇O) during the cardiopulmonary exercise test from Week 0 (baseline) to Week 12. Secondary endpoints will be time-dependent changes in peak V̇O from Week 0 to Weeks 12 and 24. Adverse events will also be evaluated. The EXCILE-HF trial will provide meaningful information regarding the effects of ivabradine on exercise tolerance in patients with HFrEF receiving standard drug therapies and suggestions for the initiation of ivabradine treatment.
静息心率较高是心血管疾病患者死亡和发病的独立危险因素。伊伐布雷定可选择性抑制If电流，降低心率，而不影响心脏传导、心肌收缩力或血压。对于接受标准药物治疗的射血分数降低的心力衰竭（HFrEF）患者，伊伐布雷定对运动耐量的影响尚不清楚。这项针对窦性心律静息心率≥75次/分钟且接受标准药物治疗的HFrEF患者的多中心干预试验将包括两个阶段：一个为期12周的开放标签、随机、平行组干预期（标准药物治疗+伊伐布雷定组和标准药物治疗组），以比较两组之间运动耐量的变化；以及一个为期12周的所有患者开放标签伊伐布雷定治疗期，以评估加用伊伐布雷定对运动耐量的影响。主要终点将是从第0周（基线）到第12周心肺运动试验期间峰值摄氧量（V̇O）的变化。次要终点将是从第0周到第12周和第24周峰值V̇O的时间依赖性变化。还将评估不良事件。EXCILE-HF试验将提供有关伊伐布雷定对接受标准药物治疗的HFrEF患者运动耐量影响的有意义信息，以及伊伐布雷定治疗起始的建议。
