非缺血性心力衰竭患者应用伊伐布雷定的有效性与安全性评价

摘要/Abstract

摘要： 目的探讨伊伐布雷定对不同病因非缺血性心力衰竭(HF,简称心衰)患者的临床疗效。方法对2018年1月至2020年2月在北京协和医院就诊、左室射血分数(LVEF)小于50%,且服用伊伐布雷定至少3个月的非缺血性心衰患者进行单中心回顾性病例分析。结果 38例患者(男性24例)中位年龄31.5(26.0~44.0)岁,分为原发性(n=17)与继发性(n=21)心肌病两组。伊伐布雷定起始剂量为5 mg/d的患者最多(65.8%),3月后耐受剂量为10~15 mg/d 的患者比例为57.9%,停药6例。整体患者平均心率从(93.7±13.5)次/min降至(75.9±12.4)次/min,其中继发性心肌病组从(99.0±11.4)次/min降至(78.6±13.8)次/min(P＜0.001),血压无显著变化。治疗后,两组的纽约心脏病协会(NYHA)心功能分级、左室舒张末内径及LVEF均显著改善(P＜0.05)。中位随访9.5个月,其中死亡4例,均为继发性心肌病患者;心衰再入院13例,其中继发性心肌病组10例,高于原发性心肌病组(47.6% vs 17.6%)(P＜0.001);仅有1例患者出现伊伐布雷定相关的心动过缓。结论伊伐布雷定能够安全有效应用于非缺血性心衰患者,减慢心率并改善心功能。尤其适用于系统性疾病伴窦性心动过速的继发性心衰患者。

关键词: 伊伐布雷定, 心肌病, 心力衰竭

Abstract: Objective To investigate the efficacy and safety of ivabradine on cardiomyopathy and heart failure(HF) with non-ischemic etiology. Methods A single-center retrospective study was carried out. Patients who admitted to Peking Union Medical College Hospital from January 2018 to February 2020, with non-ischemic heart failure, left ventricular ejection fraction (LVEF) less than 50%, and treatment of ivabradine for at least 3 months were enrolled. Results Thirty-eight patients (24 males), with a median age of 31.5 (26.0-44.0) years old, were divided into primary (n=17) and secondary (n=21) cardiomyopathies groups. Ivabradine of 5 mg/d was taken in 65.8% of the patients as the initial dose, and 10-15 mg/d was tolerated in 57.9% of patients after 3 months. Six patients withdrew the ivabradine treatment. The mean value of heart rates decreased from (93.7±13.5) beats/min to (75.9±12.4) beats/min after 3 months in all patients and from (99.0±11.4) beats/min to (78.6±13.8) beats/min in the group with secondary cardiomyopathies (P＜0.001, respectively), while no significant changes in blood pressure were observed. NYHA classification, left ventricular end-diastolic diameter and LVEF were signifi- cantly improved in both groups after treatment (P＜0.05). After a median follow-up of 9.5 months, 4 patients died, all of them were patients with secondary cardiomyopathies; Thirteen patients with heart failure re-admitted to hospital, including 10 with secondary and 3 with primary cardiomyopathies (47.6% vs 17.6%,P＜0.001). Only one case of ivabradine-related bradycardia was observed. Conclusions Ivabradine is safe and effective in patients with non-ischemic cardiomyopathy to control heart rates and to improve cardiac functions, especially for heart failure secondary to systemic diseases accompanied by sinus tachycardia.

Key words: ivabradine, cardiomyopathy, heart failure

中图分类号:

R453.9

刘颖娴, 宋彦君, 陈未, 林雪, 赖晋智, 黎婧怡, 吴炜. 非缺血性心力衰竭患者应用伊伐布雷定的有效性与安全性评价[J]. 基础医学与临床, 2021, 41(11): 1637-1642.

LIU Ying-xian, SONG Yan-jun, CHEN Wei, LIN Xue, LAI Jin-zhi, LI Jing-yi, WU Wei. Efficacy and safety evaluation of ivabradine in patients with non-ischemic heart failure[J]. Basic & Clinical Medicine, 2021, 41(11): 1637-1642.

参考文献

[1]Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology(ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC[J]. Eur J Heart Fail, 2016, 18:891-975.
[2]中华医学会心血管病学分会心力衰竭学组, 中国医师协会心力衰竭专业委员会, 中华心血管病杂志编辑委员会. 中国心力衰竭诊断和治疗指南2018[J]. 中华心血管病杂志,2018,46: 760-789.
[3]Fox K, Ford I, Steg PG, et al. Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a randomised, double-blind, placebo-controlled trial[J]. Lancet, 2008, 372:807-816.
[4]Swedberg K, Komajda M, Böhm M, et al. Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study[J]. Lancet, 2010, 376:875-885.
[5]Raja DC, Kapoor A, Sinha A, et al. Heart rate manipulation in dilated cardiomyopathy: Assessing the role of Ivabradine[J]. Indian Heart J, 2018, 70:246-251.
[6]Abdel-Salam Z, Rayan M, Saleh A, et al. I(f) current inhibitor ivabradine in patients with idiopathic dilated cardiomyopathy: Impact on the exercise tolerance and quality of life[J]. Cardiol J, 2015, 22:227-232.
[7]Bonnet D, Berger F, Jokinen E, et al. Ivabradine in children with dilated cardiomyopathy and symptomatic chronic heart failure[J]. J Am Coll Cardiol, 2017, 70:1262-1272.
[8]Bocchi EA, Rassi S, Guimarães GV, et al. Safety profile and efficacy of ivabradine in heart failure due to Chagas heart disease: a post hoc analysis of the SHIFT trial[J]. ESC Heart Fail, 2018, 5:249-256.
[9]Haghikia A, Tongers J, Berliner D, et al. Early ivabradine treatment in patients with acute peripartum cardiomyopathy: Subanalysis of the German PPCM registry[J]. Int J Cardiol, 2016, 216:165-167.
[10]Münzel T, Knorr M, Schmidt F, et al. Airborne disease: a case of a Takotsubo cardiomyopathie as a consequence of nighttime aircraft noise exposure[J]. Eur Heart J, 2016, 37:2844. doi: 10.1093/eurheartj/ehw314.
[11]Madias JE. If channel blocker ivabradine vs. β-blockers for sinus tachycardia in patients with takotsubo syndrome[J]. Int J Cardiol, 2016, 223:877-878.
[12]高阳, 梁延春, 于海波, 等. 接受心血管植入型电子器械治疗的心力衰竭患者术后心率管理的研究[J]. 中华心血管病杂志,2018,46: 173-177.
[13]Adorisio R, Calvieri C, Cantarutti N, et al. Heart rate reduction strategy using ivabradine in end-stage Duchenne cardiomyopathy[J]. Int J Cardiol, 2019, 280:99-103.
[14]Raymond-Paquin A, Nattel S, Wakili R, et al. Mechanisms and clinical significance of arrhythmia-induced cardiomyopathy[J]. Can J Cardiol, 2018, 34:1449-1460.
[15]Sugumar H, Prabhu S, Voskoboinik A, et al. Arrhythmia induced cardiomyopathy[J]. J Arrhythm, 2018, 34:376-383.
[16]Mueller KAL, Heinzmann D, Klingel K, et al. Histopathological and immunological characteristics of tachycardia-induced cardiomyopathy[J]. J Am Coll Cardiol, 2017, 69:2160-2172.
[17]Rohm I, Kretzschmar D, Pistulli R, et al. Impact of ivabradine on inflammatory markers in chronic heart failure[J]. J Immunol Res, 2016, 2016:6949320. doi: 10.1155/2016/6949320.
[18]Busseuil D, Shi Y, Mecteau M, et al. Heart rate reduction by ivabradine reduces diastolic dysfunction and cardiac fibrosis[J]. Cardiology, 2010, 117:234-242.
[19]Li YC, Chen GY, Ge LS, et al. The protective effects of ivabradine in preventing progression from viral myocarditis to dilated cardiomyopathy[J]. Front Pharmacol, 2016, 7:408. doi: 10.3389/fphar.2016.00408.
[20]Wu W, Zhang LX, Zhao JL, et al. Early short-term ivabradine treatment in new-onset acute systolic heart failure and sinus tachycardia patients with inflammatory rheu-matic disease[J]. Exp Ther Med, 2019, 18:305-311.