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, 張國紅, 韓慧媛. 伊伐布雷定治療慢性心力衰竭療效與安全性的 Meta 分析. 中國藥物與臨床, 2018, 18(3): 377-379.
2.	陳偉偉, 高潤霖, 劉力生, 等. 《中國心血管病報告 2017》概要. 中國循環雜志, 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, 曹明強, 李曉波, 等. 伊伐布雷定治療急性心肌梗死合并心力衰竭的療效. 江蘇醫藥, 2018, 44(12): 1428-1431.
8.	時珊珊, 吳曉羽. 伊伐布雷定在心血管疾病中的臨床研究進展. 中國循環雜志, 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.	羅穎, 胡鵬飛, 俞煒煒, 等. 伊伐布雷定治療慢性心力衰竭臨床療效 Meta 分析. 中國循環雜志, 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.	馬振. 硫酸氫伊伐布雷定對中—重度慢性心衰并左心室收縮功能不全患者療效研究. 山東: 濟南大學, 2016.
21.	張錚. 伊伐布雷定治療慢性阻塞性肺疾病合并心力衰竭患者的療效觀察. 中國循證心血管醫學雜志, 2018, 10(12): 1530-1533.
22.	楊溫籐, 林小君, 鄭毅, 等. 伊伐布雷定治療慢性心力衰竭的臨床療效及對血流動力學、血管內皮功能、炎性因子的影響. 中國衛生檢驗雜志, 2019, 29(3): 337-340, 350.
23.	程麗丹, 江一唱, 晏凱利, 等. 伊伐布雷定聯合常規治療慢性心力衰竭的療效與安全性觀察. 藥物流行病學雜志, 2017, 26(9): 589-592.
24.	黃覬, 錢海燕, 胡志成, 等. 伊伐布雷定對老年慢性心力衰竭患者的療效及其對胱抑素 C 的影響. 疑難病雜志, 2017, 16(6): 545-549.
25.	馬建林, 王曉紅, 李春梅, 等. 依普利酮與伊伐布雷定治療慢性心力衰竭療效及其對血 TNF-α, IL-6, BNP 水平的影響. 疑難病雜志, 2017, 16(10): 985-988.
26.	毛慶, 梁秀琳, 招曉俊, 等. 伊伐布雷定治療慢性心力衰竭的效果及對生物標記物的影響. 現代醫學, 2018, 46(9): 1017-1021.
27.	沈利霞, 文俊杰. 伊伐布雷定治療老年心力衰竭的療效及對 NT-proBNP, sST2, Galectin-3 的影響. 實用藥物與臨床, 2018, 21(5): 526-529.
28.	王群, 林文華. 伊伐布雷定治療慢性收縮性心力衰竭的效果. 心臟雜志, 2018, 30(2): 192-195.
29.	王群, 林文華. 伊伐布雷定治療慢性心力衰竭的效果. 青島大學醫學院學報, 2017, 53(6): 664-667.
30.	姚玲玲, 金銀生, 覃駿. 伊伐布雷定治療慢性收縮性心力衰竭的臨床療效觀察. 北京, 2016.
31.	岳麗賓. 硫酸氫伊伐布雷定緩釋片治療老年慢性心力衰竭患者有效性及安全性研究. 濟南大學, 2016.
32.	鄒金林, 王紅娜, 方波, 等. 伊伐布雷定對慢性心力衰竭伴持續性心房顫動患者的療效. 心腦血管病防治, 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.	陳光. 伊伐布雷定治療老年心力衰竭患者的療效觀察. 中國醫藥科學, 2017, 7(17): 82-84.
36.	胡大一, 黃德嘉, 袁祖貽, 等. 鹽酸伊伐布雷定治療中國慢性心力衰竭患者的有效性及安全性評價: SHIFT 研究中國亞組數據分析. 中華心血管病雜志, 2017, 45(3): 190-197.
37.	黃琨, 馬威, 鄭川燕, 等. 伊伐布雷定治療中重度慢性心力衰竭伴竇性心動過速的臨床研究. 臨床心血管病雜志, 2017, 33(9): 841-845.
38.	叢占春. 慢性收縮性心力衰竭應用伊伐布雷定治療的效果評定. 中國實用醫藥, 2018, 13(36): 113-114.
39.	B?hm 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.	李傳榮, 姜東炬. 伊伐布雷定在心血管疾病中的研究進展. 心血管病學進展, 2019, 40(1): 143-145.
41.	黃國鵬, 安素. N 末端 B 型利鈉肽原對老年心力衰竭臨床應用價值的研究. 中國循環雜志, 2014, 29(9): 698-701.

1. 屈巧芳, 張國紅, 韓慧媛. 伊伐布雷定治療慢性心力衰竭療效與安全性的 Meta 分析. 中國藥物與臨床, 2018, 18(3): 377-379.
2. 陳偉偉, 高潤霖, 劉力生, 等. 《中國心血管病報告 2017》概要. 中國循環雜志, 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, 曹明強, 李曉波, 等. 伊伐布雷定治療急性心肌梗死合并心力衰竭的療效. 江蘇醫藥, 2018, 44(12): 1428-1431.
8. 時珊珊, 吳曉羽. 伊伐布雷定在心血管疾病中的臨床研究進展. 中國循環雜志, 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. 羅穎, 胡鵬飛, 俞煒煒, 等. 伊伐布雷定治療慢性心力衰竭臨床療效 Meta 分析. 中國循環雜志, 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. 馬振. 硫酸氫伊伐布雷定對中—重度慢性心衰并左心室收縮功能不全患者療效研究. 山東: 濟南大學, 2016.
21. 張錚. 伊伐布雷定治療慢性阻塞性肺疾病合并心力衰竭患者的療效觀察. 中國循證心血管醫學雜志, 2018, 10(12): 1530-1533.
22. 楊溫籐, 林小君, 鄭毅, 等. 伊伐布雷定治療慢性心力衰竭的臨床療效及對血流動力學、血管內皮功能、炎性因子的影響. 中國衛生檢驗雜志, 2019, 29(3): 337-340, 350.
23. 程麗丹, 江一唱, 晏凱利, 等. 伊伐布雷定聯合常規治療慢性心力衰竭的療效與安全性觀察. 藥物流行病學雜志, 2017, 26(9): 589-592.
24. 黃覬, 錢海燕, 胡志成, 等. 伊伐布雷定對老年慢性心力衰竭患者的療效及其對胱抑素 C 的影響. 疑難病雜志, 2017, 16(6): 545-549.
25. 馬建林, 王曉紅, 李春梅, 等. 依普利酮與伊伐布雷定治療慢性心力衰竭療效及其對血 TNF-α, IL-6, BNP 水平的影響. 疑難病雜志, 2017, 16(10): 985-988.
26. 毛慶, 梁秀琳, 招曉俊, 等. 伊伐布雷定治療慢性心力衰竭的效果及對生物標記物的影響. 現代醫學, 2018, 46(9): 1017-1021.
27. 沈利霞, 文俊杰. 伊伐布雷定治療老年心力衰竭的療效及對 NT-proBNP, sST2, Galectin-3 的影響. 實用藥物與臨床, 2018, 21(5): 526-529.
28. 王群, 林文華. 伊伐布雷定治療慢性收縮性心力衰竭的效果. 心臟雜志, 2018, 30(2): 192-195.
29. 王群, 林文華. 伊伐布雷定治療慢性心力衰竭的效果. 青島大學醫學院學報, 2017, 53(6): 664-667.
30. 姚玲玲, 金銀生, 覃駿. 伊伐布雷定治療慢性收縮性心力衰竭的臨床療效觀察. 北京, 2016.
31. 岳麗賓. 硫酸氫伊伐布雷定緩釋片治療老年慢性心力衰竭患者有效性及安全性研究. 濟南大學, 2016.
32. 鄒金林, 王紅娜, 方波, 等. 伊伐布雷定對慢性心力衰竭伴持續性心房顫動患者的療效. 心腦血管病防治, 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. 陳光. 伊伐布雷定治療老年心力衰竭患者的療效觀察. 中國醫藥科學, 2017, 7(17): 82-84.
36. 胡大一, 黃德嘉, 袁祖貽, 等. 鹽酸伊伐布雷定治療中國慢性心力衰竭患者的有效性及安全性評價: SHIFT 研究中國亞組數據分析. 中華心血管病雜志, 2017, 45(3): 190-197.
37. 黃琨, 馬威, 鄭川燕, 等. 伊伐布雷定治療中重度慢性心力衰竭伴竇性心動過速的臨床研究. 臨床心血管病雜志, 2017, 33(9): 841-845.
38. 叢占春. 慢性收縮性心力衰竭應用伊伐布雷定治療的效果評定. 中國實用醫藥, 2018, 13(36): 113-114.
39. B?hm 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. 李傳榮, 姜東炬. 伊伐布雷定在心血管疾病中的研究進展. 心血管病學進展, 2019, 40(1): 143-145.
41. 黃國鵬, 安素. N 末端 B 型利鈉肽原對老年心力衰竭臨床應用價值的研究. 中國循環雜志, 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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