Efficacy and safety of ivabradine for patients with chronic heart failure: a meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

YUN Lixin ¹ , ZHU Jieyun ² , ZHONG Zhimei ² , ZHANG Jianfeng ³ ,  LEI Zhuoqing ³

1. Department of Cardiology, the Second Affiliated Hospital of Guangxi Medical University, Nanning, 530007, P.R.China;
2. Graduate School of Guangxi Medical University, Nanning, 530021, P.R.China;
3. Department of General Medicine, the Second Affiliated Hospital of Guangxi Medical University, Nanning, 530007, P.R.China;

Corresponding author：

LEI Zhuoqing, Email: 948727194@qq.com

Keywords：

Ivabradine; Chronic heart failure; Meta-analysis; Systematic review; Randomized controlled trial

DOI：

10.7507/1672-2531.201906036

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objectives To systematically review the efficacy and safety of ivabradine (IVA) for patients with chronic heart failure (CHF).Methods PubMed, EMbase, The Cochrane Library, CNKI, WanFang Data and VIP databases were electronically searched to collect randomized controlled trials (RCTs) on the efficacy and safety of IVA for patients with CHF from inception to April, 2019. Two reviewers independently screened literature, extracted data and assessed risk of bias of included studies, then, meta-analysis was performed using Stata 12.0 software.Results A total of 22 RCTs involving 2 010 patients were included. The results of meta-analysis showed that, compared with control group, IVA group could decrease heart rate (HR) (WMD=−10.58, 95%CI −12.47 to −8.69, P=0.000) and N-terminal probrain natriuretic peptide (NT-proBNP) (WMD=−457.87, 95%CI −842.63 to −73.11, P=0.020). IVA group was superior in 6 minutes’ walk distance (6MWD) (WMD=40.49, 95%CI 27.83 to 53.15, P=0.000), left ventricular ejection fraction (LVEF) (WMD=5.11, 95%CI 3.74 to 6.48, P=0.000), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular end-diastolic dimension (LVEDd), left ventricular end-systolic dimension (LVESd) and incidence of endpoint events with significant difference. However, the total effective rate, the incidence of adverse reactions and blood pressures were similar between two groups.Conclusion Current evidence shows that IVA could significantly reduce HR, improve cardiac function and exercise tolerance in CHF patients with no significant increase of adverse events. Due to limited quality and quantity of the included studies, more high-quality studies are required to verify above conclusions.

Citation： YUN Lixin, ZHU Jieyun, ZHONG Zhimei, ZHANG Jianfeng, LEI Zhuoqing. Efficacy and safety of ivabradine for patients with chronic heart failure: a meta-analysis. Chinese Journal of Evidence-Based Medicine, 2019, 19(11): 1276-1285. doi: 10.7507/1672-2531.201906036 Copy

1.	屈巧芳, 张国红, 韩慧媛. 伊伐布雷定治疗慢性心力衰竭疗效与安全性的 Meta 分析. 中国药物与临床, 2018, 18(3): 377-379.
2.	陈伟伟, 高润霖, 刘力生, 等. 《中国心血管病报告 2017》概要. 中国循环杂志, 2018, 33(1): 1-8.
3.	Thorup L, Simonsen U, Grimm D, et al. Ivabradine: current and future treatment of heart failure. Basic Clin Pharmacol Toxicol, 2017, 121(2): 89-97.
4.	Badu-Boateng C, Jennings R, Hammersley D. The therapeutic role of ivabradine in heart failure. Ther Adv Chronic Dis, 2018, 9(11): 199-207.
5.	Tjugen TB, Flaa A, Kjeldsen SE. The prognostic significance of heart rate for cardiovascular disease and hypertension. Curr Hypertens Rep, 2010, 12(3): 162-169.
6.	Tsutsui H, Momomura S, Yamashina A, et al. Heart rate control with if inhibitor, ivabradine, in Japanese Patients with chronic heart failure- a randomized, double-blind, placebo-controlled phase Ⅱ Study. Circ J, 2016, 80(3): 668-676.
7.	胡圣大, 曹明强, 李晓波, 等. 伊伐布雷定治疗急性心肌梗死合并心力衰竭的疗效. 江苏医药, 2018, 44(12): 1428-1431.
8.	时珊珊, 吴晓羽. 伊伐布雷定在心血管疾病中的临床研究进展. 中国循环杂志, 2015, 30(6): 613-616.
9.	Bocchi EA, Salemi VMC. Ivabradine for treatment of heart failure. Expert Opin Drug Saf, 2019, 18(5): 393-402.
10.	罗颖, 胡鹏飞, 俞炜炜, 等. 伊伐布雷定治疗慢性心力衰竭临床疗效 Meta 分析. 中国循环杂志, 2017, 32(10): 960-964.
11.	Hidalgo FJ, Anguita M, Castillo JC, et al. Effect of early treatment with ivabradine combined with beta-blockers versus beta-blockers alone in patients hospitalised with heart failure and reduced left ventricular ejection fraction (ETHIC-AHF): a randomised study. Int J Cardiol, 2016, 217(1): 7-11.
12.	Volterrani M, Cice G, Caminiti G, et al. Effect of carvedilol, ivabradine or their combination on exercise capacity in patients with heart failure (the CARVIVA HF trial). Int J Cardiol, 2011, 151(2): 218-224.
13.	Mansour S, Youssef A, Rayan M, et al. Efficacy of ivabradine in idiopathic dilated cardiomyopathy patients with chronic heart failure. Egyptian Heart J, 2011, 63(2): 79-85.
14.	Sarullo FM, Fazio G, Puccio D, et al. Impact of ''off-label'' use of ivabradine on exercise capacity, gas exchange, functional class, quality of life, and neurohormonal modulation in patients with ischemic chronic heart failure. J Cardiovasc Pharmacol Ther, 2010, 15(4): 349-355.
15.	Ordu S, Yildiz BS, Alihanoglu YI, et al. Effects of ivabradine therapy on heart failure biomarkers. Cardiol J, 2015, 22(5): 501-509.
16.	Ceconi C, Freedman SB, Tardif JC, et al. Effect of heart rate reduction by ivabradine on left ventricular remodeling in the echocardiographic substudy of BEAUTIFUL. Int J Cardiol, 2011, 146(3): 408-414.
17.	Abdel-Salam Z, Rayan M, Saleh A, et al. If current inhibitor ivabradine in patients with idiopathic dilated cardiomyopathy: impact on the exercise tolerance and quality of life. Cardiol J, 2015, 22(2): 227-232.
18.	Raja DC, Kapoor A, Sinha A, et al. Heart rate manipulation in dilated cardiomyopathy: assessing the role of ivabradine. Indian Heart J, 2018, 70(2): 246-251.
19.	Villacorta AS, Villacorta H, Caldas JA, et al. Effects of heart rate reduction with either pyridostigmine or ivabradine in patients with heart failure: a randomized, double-blind study. J Cardiovasc Pharmacol Ther, 2019, 24(2): 139-145.
20.	马振. 硫酸氢伊伐布雷定对中—重度慢性心衰并左心室收缩功能不全患者疗效研究. 山东: 济南大学, 2016.
21.	张铮. 伊伐布雷定治疗慢性阻塞性肺疾病合并心力衰竭患者的疗效观察. 中国循证心血管医学杂志, 2018, 10(12): 1530-1533.
22.	杨温籐, 林小君, 郑毅, 等. 伊伐布雷定治疗慢性心力衰竭的临床疗效及对血流动力学、血管内皮功能、炎性因子的影响. 中国卫生检验杂志, 2019, 29(3): 337-340, 350.
23.	程丽丹, 江一唱, 晏凯利, 等. 伊伐布雷定联合常规治疗慢性心力衰竭的疗效与安全性观察. 药物流行病学杂志, 2017, 26(9): 589-592.
24.	黄觊, 钱海燕, 胡志成, 等. 伊伐布雷定对老年慢性心力衰竭患者的疗效及其对胱抑素 C 的影响. 疑难病杂志, 2017, 16(6): 545-549.
25.	马建林, 王晓红, 李春梅, 等. 依普利酮与伊伐布雷定治疗慢性心力衰竭疗效及其对血 TNF-α, IL-6, BNP 水平的影响. 疑难病杂志, 2017, 16(10): 985-988.
26.	毛庆, 梁秀琳, 招晓俊, 等. 伊伐布雷定治疗慢性心力衰竭的效果及对生物标记物的影响. 现代医学, 2018, 46(9): 1017-1021.
27.	沈利霞, 文俊杰. 伊伐布雷定治疗老年心力衰竭的疗效及对 NT-proBNP, sST2, Galectin-3 的影响. 实用药物与临床, 2018, 21(5): 526-529.
28.	王群, 林文华. 伊伐布雷定治疗慢性收缩性心力衰竭的效果. 心脏杂志, 2018, 30(2): 192-195.
29.	王群, 林文华. 伊伐布雷定治疗慢性心力衰竭的效果. 青岛大学医学院学报, 2017, 53(6): 664-667.
30.	姚玲玲, 金银生, 覃骏. 伊伐布雷定治疗慢性收缩性心力衰竭的临床疗效观察. 北京, 2016.
31.	岳丽宾. 硫酸氢伊伐布雷定缓释片治疗老年慢性心力衰竭患者有效性及安全性研究. 济南大学, 2016.
32.	邹金林, 王红娜, 方波, 等. 伊伐布雷定对慢性心力衰竭伴持续性心房颤动患者的疗效. 心脑血管病防治, 2018, 18(5): 388-390.
33.	Ziaeian B, Fonarow GC. Epidemiology and aetiology of heart failure. Nat Rev Cardiol, 2016, 13(6): 368-378.
34.	Laskey WK, Alomari I, Cox M, et al. Heart rate at hospital discharge in patients with heart failure is associated with mortality and rehospitalization. J Am Heart Assoc, 2015, 4(4): e001626.
35.	陈光. 伊伐布雷定治疗老年心力衰竭患者的疗效观察. 中国医药科学, 2017, 7(17): 82-84.
36.	胡大一, 黄德嘉, 袁祖贻, 等. 盐酸伊伐布雷定治疗中国慢性心力衰竭患者的有效性及安全性评价: SHIFT 研究中国亚组数据分析. 中华心血管病杂志, 2017, 45(3): 190-197.
37.	黄琨, 马威, 郑川燕, 等. 伊伐布雷定治疗中重度慢性心力衰竭伴窦性心动过速的临床研究. 临床心血管病杂志, 2017, 33(9): 841-845.
38.	丛占春. 慢性收缩性心力衰竭应用伊伐布雷定治疗的效果评定. 中国实用医药, 2018, 13(36): 113-114.
39.	Böhm M, Swedberg K, Komajda M, et al. Heart rate as a risk factor in chronic heart failure (SHIFT): the association between heart rate and outcomes in a randomised placebo-controlled trial. Lancet, 2010, 376(9744): 886-894.
40.	李传荣, 姜东炬. 伊伐布雷定在心血管疾病中的研究进展. 心血管病学进展, 2019, 40(1): 143-145.
41.	黄国鹏, 安素. N 末端 B 型利钠肽原对老年心力衰竭临床应用价值的研究. 中国循环杂志, 2014, 29(9): 698-701.

1. 屈巧芳, 张国红, 韩慧媛. 伊伐布雷定治疗慢性心力衰竭疗效与安全性的 Meta 分析. 中国药物与临床, 2018, 18(3): 377-379.
2. 陈伟伟, 高润霖, 刘力生, 等. 《中国心血管病报告 2017》概要. 中国循环杂志, 2018, 33(1): 1-8.
3. Thorup L, Simonsen U, Grimm D, et al. Ivabradine: current and future treatment of heart failure. Basic Clin Pharmacol Toxicol, 2017, 121(2): 89-97.
4. Badu-Boateng C, Jennings R, Hammersley D. The therapeutic role of ivabradine in heart failure. Ther Adv Chronic Dis, 2018, 9(11): 199-207.
5. Tjugen TB, Flaa A, Kjeldsen SE. The prognostic significance of heart rate for cardiovascular disease and hypertension. Curr Hypertens Rep, 2010, 12(3): 162-169.
6. Tsutsui H, Momomura S, Yamashina A, et al. Heart rate control with if inhibitor, ivabradine, in Japanese Patients with chronic heart failure- a randomized, double-blind, placebo-controlled phase Ⅱ Study. Circ J, 2016, 80(3): 668-676.
7. 胡圣大, 曹明强, 李晓波, 等. 伊伐布雷定治疗急性心肌梗死合并心力衰竭的疗效. 江苏医药, 2018, 44(12): 1428-1431.
8. 时珊珊, 吴晓羽. 伊伐布雷定在心血管疾病中的临床研究进展. 中国循环杂志, 2015, 30(6): 613-616.
9. Bocchi EA, Salemi VMC. Ivabradine for treatment of heart failure. Expert Opin Drug Saf, 2019, 18(5): 393-402.
10. 罗颖, 胡鹏飞, 俞炜炜, 等. 伊伐布雷定治疗慢性心力衰竭临床疗效 Meta 分析. 中国循环杂志, 2017, 32(10): 960-964.
11. Hidalgo FJ, Anguita M, Castillo JC, et al. Effect of early treatment with ivabradine combined with beta-blockers versus beta-blockers alone in patients hospitalised with heart failure and reduced left ventricular ejection fraction (ETHIC-AHF): a randomised study. Int J Cardiol, 2016, 217(1): 7-11.
12. Volterrani M, Cice G, Caminiti G, et al. Effect of carvedilol, ivabradine or their combination on exercise capacity in patients with heart failure (the CARVIVA HF trial). Int J Cardiol, 2011, 151(2): 218-224.
13. Mansour S, Youssef A, Rayan M, et al. Efficacy of ivabradine in idiopathic dilated cardiomyopathy patients with chronic heart failure. Egyptian Heart J, 2011, 63(2): 79-85.
14. Sarullo FM, Fazio G, Puccio D, et al. Impact of ''off-label'' use of ivabradine on exercise capacity, gas exchange, functional class, quality of life, and neurohormonal modulation in patients with ischemic chronic heart failure. J Cardiovasc Pharmacol Ther, 2010, 15(4): 349-355.
15. Ordu S, Yildiz BS, Alihanoglu YI, et al. Effects of ivabradine therapy on heart failure biomarkers. Cardiol J, 2015, 22(5): 501-509.
16. Ceconi C, Freedman SB, Tardif JC, et al. Effect of heart rate reduction by ivabradine on left ventricular remodeling in the echocardiographic substudy of BEAUTIFUL. Int J Cardiol, 2011, 146(3): 408-414.
17. Abdel-Salam Z, Rayan M, Saleh A, et al. If current inhibitor ivabradine in patients with idiopathic dilated cardiomyopathy: impact on the exercise tolerance and quality of life. Cardiol J, 2015, 22(2): 227-232.
18. Raja DC, Kapoor A, Sinha A, et al. Heart rate manipulation in dilated cardiomyopathy: assessing the role of ivabradine. Indian Heart J, 2018, 70(2): 246-251.
19. Villacorta AS, Villacorta H, Caldas JA, et al. Effects of heart rate reduction with either pyridostigmine or ivabradine in patients with heart failure: a randomized, double-blind study. J Cardiovasc Pharmacol Ther, 2019, 24(2): 139-145.
20. 马振. 硫酸氢伊伐布雷定对中—重度慢性心衰并左心室收缩功能不全患者疗效研究. 山东: 济南大学, 2016.
21. 张铮. 伊伐布雷定治疗慢性阻塞性肺疾病合并心力衰竭患者的疗效观察. 中国循证心血管医学杂志, 2018, 10(12): 1530-1533.
22. 杨温籐, 林小君, 郑毅, 等. 伊伐布雷定治疗慢性心力衰竭的临床疗效及对血流动力学、血管内皮功能、炎性因子的影响. 中国卫生检验杂志, 2019, 29(3): 337-340, 350.
23. 程丽丹, 江一唱, 晏凯利, 等. 伊伐布雷定联合常规治疗慢性心力衰竭的疗效与安全性观察. 药物流行病学杂志, 2017, 26(9): 589-592.
24. 黄觊, 钱海燕, 胡志成, 等. 伊伐布雷定对老年慢性心力衰竭患者的疗效及其对胱抑素 C 的影响. 疑难病杂志, 2017, 16(6): 545-549.
25. 马建林, 王晓红, 李春梅, 等. 依普利酮与伊伐布雷定治疗慢性心力衰竭疗效及其对血 TNF-α, IL-6, BNP 水平的影响. 疑难病杂志, 2017, 16(10): 985-988.
26. 毛庆, 梁秀琳, 招晓俊, 等. 伊伐布雷定治疗慢性心力衰竭的效果及对生物标记物的影响. 现代医学, 2018, 46(9): 1017-1021.
27. 沈利霞, 文俊杰. 伊伐布雷定治疗老年心力衰竭的疗效及对 NT-proBNP, sST2, Galectin-3 的影响. 实用药物与临床, 2018, 21(5): 526-529.
28. 王群, 林文华. 伊伐布雷定治疗慢性收缩性心力衰竭的效果. 心脏杂志, 2018, 30(2): 192-195.
29. 王群, 林文华. 伊伐布雷定治疗慢性心力衰竭的效果. 青岛大学医学院学报, 2017, 53(6): 664-667.
30. 姚玲玲, 金银生, 覃骏. 伊伐布雷定治疗慢性收缩性心力衰竭的临床疗效观察. 北京, 2016.
31. 岳丽宾. 硫酸氢伊伐布雷定缓释片治疗老年慢性心力衰竭患者有效性及安全性研究. 济南大学, 2016.
32. 邹金林, 王红娜, 方波, 等. 伊伐布雷定对慢性心力衰竭伴持续性心房颤动患者的疗效. 心脑血管病防治, 2018, 18(5): 388-390.
33. Ziaeian B, Fonarow GC. Epidemiology and aetiology of heart failure. Nat Rev Cardiol, 2016, 13(6): 368-378.
34. Laskey WK, Alomari I, Cox M, et al. Heart rate at hospital discharge in patients with heart failure is associated with mortality and rehospitalization. J Am Heart Assoc, 2015, 4(4): e001626.
35. 陈光. 伊伐布雷定治疗老年心力衰竭患者的疗效观察. 中国医药科学, 2017, 7(17): 82-84.
36. 胡大一, 黄德嘉, 袁祖贻, 等. 盐酸伊伐布雷定治疗中国慢性心力衰竭患者的有效性及安全性评价: SHIFT 研究中国亚组数据分析. 中华心血管病杂志, 2017, 45(3): 190-197.
37. 黄琨, 马威, 郑川燕, 等. 伊伐布雷定治疗中重度慢性心力衰竭伴窦性心动过速的临床研究. 临床心血管病杂志, 2017, 33(9): 841-845.
38. 丛占春. 慢性收缩性心力衰竭应用伊伐布雷定治疗的效果评定. 中国实用医药, 2018, 13(36): 113-114.
39. Böhm M, Swedberg K, Komajda M, et al. Heart rate as a risk factor in chronic heart failure (SHIFT): the association between heart rate and outcomes in a randomised placebo-controlled trial. Lancet, 2010, 376(9744): 886-894.
40. 李传荣, 姜东炬. 伊伐布雷定在心血管疾病中的研究进展. 心血管病学进展, 2019, 40(1): 143-145.
41. 黄国鹏, 安素. N 末端 B 型利钠肽原对老年心力衰竭临床应用价值的研究. 中国循环杂志, 2014, 29(9): 698-701.

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Efficacy and safety of ivabradine for patients with chronic heart failure: a meta-analysis

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