Efficacy and Safety of Different Doses of Metoprolol for Patients with Chronic Heart Failure_Chinese Journal of Evidence-Based Medicine

Authors：

ZHOU Yan ¹ , YANG Ming ¹ , CHEN Tao ² ,  DONG Birong ¹

1. Geriatric Department of West China Hospital, Sichuan University, Chengdu 610041, China2. School of Insurance, Southwest University of Finance and Economics, Chengdu 610071, China;

Corresponding author：

DONG Birong, Email: birongdong@hotmail.com

Keywords：

Metoprolol; Chronic heart failure; Efficacy; Safety

Video：

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Objective 　To access the efficacy and safety of different doses of metoprolol for patients with chronic heart failure.
Methods 　We searched databases such as MEDLINE, EMbase, The Cochrane Library, CBM and CMCC. The search was conducted in March 2006. Randomised controlled trials, systematic reviews, and current guidelines of chronic heart failure were reviewed. The efficacy and safety of the high-dose (≥100 mg/d) and low-dose metoprolol ( lt;100 mg/d) were compared.
Results 　Only one small-scale, short-term randomised trial met our inclusion criteria. This found that metoprolol 100 mg/d was more effective than 25 mg/d and 50 mg/d. A sub-group analysis of MERIT-HF recommended individualized titration for drug administration. Most guidelines suggested that the administration of metoprolol CR/XL for chronic left ventricular systolic dysfunction should be performed by titrating up to 200 mg/d or the maximum tolerance dose. Patients receiving 100 mg/d might have more adverse events than those receiving a lower dose than this. However, in the long-term, it’s the benefits of high-dose treatment outweighed its risks. Race-related differences in tolerance or dose-related adverse effects were not found.
Conclusion 　We couldn’t determine an optimal dose based on the existing evidence, but a target dose of metoprolol CR/XL 200 mg/d is safe and effective. We are unable to draw any conclusions about the relationship between dose and adverse effects.

Citation： ZHOU Yan,YANG Ming,CHEN Tao,DONG Birong. Efficacy and Safety of Different Doses of Metoprolol for Patients with Chronic Heart Failure. Chinese Journal of Evidence-Based Medicine, 2007, 07(6): 472-477. doi: Copy

1.	Chinese Society of Cardiovascular Diseases of Chinese Medical Association, the Editorial Board of Chinese Journal of Cardiology. Recommendations for the management of chronic heart failure. Chinese Journal of Cardiology, 2002, 30(1): 7-23.
2.	Yu Q, Li DW, Pu SY. Different dose of metoprolol for congestive heart failure. The Journal of Clinical Cardiology, 1997, 13(6): 367.
3.	Liu XZ, Liu YS. Analysis on efficacy of betaloc treating 39 patients with hyperthyriod cardiac disease with heart failure. Mod Diagn Treat, 2003, 14(3): 149.
4.	Zhu XD. Effects of different doses of betaloc on diastolic heart failure. Clinical Medicine of China, 2004, 20(11): 970-972.
5.	Gao ZG, Du YZ, Ren GC. Comparative observation of different doses of metoprolol tartrate for chronic heart failure. Chinese Remedies & Clinics, 2005, 5(1): 63-64.
6.	Li ZK, Mei X, Zhu SJ, et al. Different doses of metoprolol for ventricular remolding and cardiovascular events in patients with chronic heart failure. Chin J Cardiol, 2004, 32(10): 892.
7.	Shi X. Comparative observation on the effects and tolerance of different doses ofmetoprolol in the treatment of chronic congestive heart failure. Chin J Diffic and Compl Cas, 2005, 4(1): 7-9.
8.	Wang L. Clinical observation of different doses of metoprolol for chronic heart failure. Modern Medicine & Health, 2005,21(17)：2289-2290.
9.	Zou JJ, Li YC, Zhang Y. Tolerant dosage range and safety study of metoprolol for severe chronic heart failure. Journal of Sichuan Continuing Education College of Ms, 2005, 24(2): 88-89.
10.	Hunt SA, Baker DW, Chin MH, et al. ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult. Bethesda (MD): American College of Cardiology Foundation (ACCF); 2001 Sep. 56.
11.	Swedberg K, Cleland J, Dargie H, et al. Guidelines for the diagnosis and treatment of chronic heart failure: executive summary (update 2005): The Task Force for the Diagnosis and Treatment of Chronic Heart Failure of the European Society of Cardiology. Eur Heart J, 2005, 26(11): 1115-1140.
12.	Institute for Clinical Systems Improvement (ICSI). Inpatient management of heart failure. Bloomington (MN): Institute for Clinical Systems Improvement (ICSI); 2004 Feb. 85.
13.	中华医学会心血管病分会, 中华心血管病杂志编辑委员会. 慢性收缩性心力衰竭治疗建议. 中华心血管病杂志, 2002, 30(1): 7-23.
14.	Moher D, Cook DJ, Eastwood S, et al. Improving the quality of reports of meta-analyses of randomised controlled trials: the QUOROM statement. Quality of Reporting of Meta-analyses. Lancet, 1999, 354(9193): 1896-1900.
15.	Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials, 1996, 17(1): 1-12.
16.	Wikstrand J, Hjalmarson A, Waagstein F, et al. Wallenberg Laboratory Dose of metoprolol CR/XL and clinical outcomes in patients with heart failure: analysis of the experience in metoprolol CR/XL randomized intervention trial in chronic heart failure (MERIT-HF). J Am Coll Cardiol, 2002, 40(3): 491-498.
17.	Fisher ML, Gottlieb SS, Plotnick GD, et al. Beneficial effects of metoprolol in heart failure associated with coronary artery disease: a randomized trial. J Am Coll Cardiol, 1994, 23(4 ): 943-950.
18.	Nilsson OR, Melander A, Tegler L. Effects and plasma levels of propranolol and metoprolol in hyperthyroid patients. Eur J Clin Pharmacol, 1980,18(4): 315-320.
19.	Anderson JL, Lutz JR, Gilbert EM, et al. A randomized trial of low-dose beta-blockade therapy for idiopathic dilated cardiomyopathy. Am J Cardiol, 1985, 55(4): 471-475.
20.	Goldstein S, Kennedy HL, Hall C, et al. Metoprolol CR/XL in patients with heart failure: A pilot study examining the tolerability, safety, and effect on left ventricular ejection fraction. Am Heart J, 1999, 138(6 Pt 1): 1158-1165.
21.	MERIT-HF Study Group. Effect of metoprolol CR/XL in chronic heart failure: metoprolol CR/XL randomised intervention trial in congestive heart failure (MERIT-HF). Lancet, 1999, 353(9169): 2001-2007.
22.	余强, 李德旺, 蒲世玉. 不同剂量美托洛尔治疗充血性心力衰竭疗效观察. 临床心血管病杂志, 1997, 13(6): 367.
23.	刘小珍, 刘远胜. 倍他乐克治疗39例甲亢性心脏病并心衰的疗效分析. 现代诊断与治疗, 2003, 14(3): 149.
24.	朱宣德. 不同剂量倍他乐克治疗舒张性心力衰竭的疗效观察.中国综合临床, 2004, 20(11): 970-972.
25.	高志广, 杜玉芝, 任国成. 不同剂量酒石酸美托洛尔治疗慢性心力衰竭的对比研究. 中国药物与临床, 2005, 5(1): 63-64.
26.	李振魁, 梅霞, 祝善俊, 等. 不同剂量美托洛尔对慢性心力衰竭患者心室重塑和心血管事件的影响. 中华心血管病杂志, 2004, 32(10): 892.
27.	石翔. 不同剂量美托洛尔治疗慢性充血性心力衰竭的疗效及耐受性比较观察. 疑难病杂志, 2005, 4(1): 7-9.
28.	王莉. 不同剂量美托洛尔治疗慢性充血性心力衰竭的临床疗效观察. 现代医药卫生, 2005, 21(17): 2289-2290.
29.	邹剑杰, 李永超, 张勇. 美托洛尔治疗慢性重度心力衰竭患者的耐受剂量范围和安全性研究. 四川省卫生管理干部学院学报, 2005, 24(2): 88-89.
30.	Gottlieb S, Fisher ML, Kjekshus J, on behalf of the MERIT-HF Investigators. Tolerability of beta-blocker initiation and titration in the Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure (MERIT-HF). Circulation, 2002, 105: 1182-1188.
31.	Macdonald PS, Keogh AM, Aboyoun CL, et al. Tolerability and efficacy of carvedilol in patients with New York Heart Association class IV heart failure. J Am Coll Cardiol, 1999, 33: 924-931.
32.	Waagstein F, Bristow MR, Swedberg K, et al. Beneficial effects of metoprolol in idiopathic dilated cardiomyopathy. Lancet, 1993, 342: 1441-1446.
33.	Engelmeier RS, O’Connell JB, Walsh R, et al. Improvement in symptoms and exercise tolerance by metoprolol in patients with dilated cardiomyopathy: a double-blind, randomized, placebo-controlled trial. Circulation, 1985, 72: 536-546.
34.	Fisher ML, Gottlieb SS, Plotnick GD, et al. Beneficial effects of metoprolol in heart failure associated with coronary artery disease: a randomized trial. J Am Coll Cardiol, 1994, 23: 943–950.
35.	Eichhorn EJ, Heesch CM, Barnett JH, et al. Effect of metoprolol on myocardial function and energetics in patients with nonischemic dilated cardiomyopathy: a randomized, double-blind, placebo-controlled study. J Am Coll Cardiol, 1994, 24: 1310–1320.
36.	ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation, 2001, 11, 104(24): 2996-3007.
37.	Remme WJ, Swedberg K, Task Force for the Diagnosis and Treatment of Chronic Heart Failure, European Society of Cardiology. Guidelines for the diagnosis and treatment of chronic heart failure. Eur Heart J, 2001, 22(17): 1527-1560.
38.	Poole-Wilson PA, Swedberg K, Cleland JG, et al. Comparison of carvedilol and metoprolol on clinical outcomes in patients with chronic heart failure in the Carvedilol Or Metoprolol European Trial (COMET): randomised controlled trial. Lancet, 2003, 362: 7-13.

1. Chinese Society of Cardiovascular Diseases of Chinese Medical Association, the Editorial Board of Chinese Journal of Cardiology. Recommendations for the management of chronic heart failure. Chinese Journal of Cardiology, 2002, 30(1): 7-23.
2. Yu Q, Li DW, Pu SY. Different dose of metoprolol for congestive heart failure. The Journal of Clinical Cardiology, 1997, 13(6): 367.
3. Liu XZ, Liu YS. Analysis on efficacy of betaloc treating 39 patients with hyperthyriod cardiac disease with heart failure. Mod Diagn Treat, 2003, 14(3): 149.
4. Zhu XD. Effects of different doses of betaloc on diastolic heart failure. Clinical Medicine of China, 2004, 20(11): 970-972.
5. Gao ZG, Du YZ, Ren GC. Comparative observation of different doses of metoprolol tartrate for chronic heart failure. Chinese Remedies & Clinics, 2005, 5(1): 63-64.
6. Li ZK, Mei X, Zhu SJ, et al. Different doses of metoprolol for ventricular remolding and cardiovascular events in patients with chronic heart failure. Chin J Cardiol, 2004, 32(10): 892.
7. Shi X. Comparative observation on the effects and tolerance of different doses ofmetoprolol in the treatment of chronic congestive heart failure. Chin J Diffic and Compl Cas, 2005, 4(1): 7-9.
8. Wang L. Clinical observation of different doses of metoprolol for chronic heart failure. Modern Medicine & Health, 2005,21(17)：2289-2290.
9. Zou JJ, Li YC, Zhang Y. Tolerant dosage range and safety study of metoprolol for severe chronic heart failure. Journal of Sichuan Continuing Education College of Ms, 2005, 24(2): 88-89.
10. Hunt SA, Baker DW, Chin MH, et al. ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult. Bethesda (MD): American College of Cardiology Foundation (ACCF); 2001 Sep. 56.
11. Swedberg K, Cleland J, Dargie H, et al. Guidelines for the diagnosis and treatment of chronic heart failure: executive summary (update 2005): The Task Force for the Diagnosis and Treatment of Chronic Heart Failure of the European Society of Cardiology. Eur Heart J, 2005, 26(11): 1115-1140.
12. Institute for Clinical Systems Improvement (ICSI). Inpatient management of heart failure. Bloomington (MN): Institute for Clinical Systems Improvement (ICSI); 2004 Feb. 85.
13. 中华医学会心血管病分会, 中华心血管病杂志编辑委员会. 慢性收缩性心力衰竭治疗建议. 中华心血管病杂志, 2002, 30(1): 7-23.
14. Moher D, Cook DJ, Eastwood S, et al. Improving the quality of reports of meta-analyses of randomised controlled trials: the QUOROM statement. Quality of Reporting of Meta-analyses. Lancet, 1999, 354(9193): 1896-1900.
15. Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials, 1996, 17(1): 1-12.
16. Wikstrand J, Hjalmarson A, Waagstein F, et al. Wallenberg Laboratory Dose of metoprolol CR/XL and clinical outcomes in patients with heart failure: analysis of the experience in metoprolol CR/XL randomized intervention trial in chronic heart failure (MERIT-HF). J Am Coll Cardiol, 2002, 40(3): 491-498.
17. Fisher ML, Gottlieb SS, Plotnick GD, et al. Beneficial effects of metoprolol in heart failure associated with coronary artery disease: a randomized trial. J Am Coll Cardiol, 1994, 23(4 ): 943-950.
18. Nilsson OR, Melander A, Tegler L. Effects and plasma levels of propranolol and metoprolol in hyperthyroid patients. Eur J Clin Pharmacol, 1980,18(4): 315-320.
19. Anderson JL, Lutz JR, Gilbert EM, et al. A randomized trial of low-dose beta-blockade therapy for idiopathic dilated cardiomyopathy. Am J Cardiol, 1985, 55(4): 471-475.
20. Goldstein S, Kennedy HL, Hall C, et al. Metoprolol CR/XL in patients with heart failure: A pilot study examining the tolerability, safety, and effect on left ventricular ejection fraction. Am Heart J, 1999, 138(6 Pt 1): 1158-1165.
21. MERIT-HF Study Group. Effect of metoprolol CR/XL in chronic heart failure: metoprolol CR/XL randomised intervention trial in congestive heart failure (MERIT-HF). Lancet, 1999, 353(9169): 2001-2007.
22. 余强, 李德旺, 蒲世玉. 不同剂量美托洛尔治疗充血性心力衰竭疗效观察. 临床心血管病杂志, 1997, 13(6): 367.
23. 刘小珍, 刘远胜. 倍他乐克治疗39例甲亢性心脏病并心衰的疗效分析. 现代诊断与治疗, 2003, 14(3): 149.
24. 朱宣德. 不同剂量倍他乐克治疗舒张性心力衰竭的疗效观察.中国综合临床, 2004, 20(11): 970-972.
25. 高志广, 杜玉芝, 任国成. 不同剂量酒石酸美托洛尔治疗慢性心力衰竭的对比研究. 中国药物与临床, 2005, 5(1): 63-64.
26. 李振魁, 梅霞, 祝善俊, 等. 不同剂量美托洛尔对慢性心力衰竭患者心室重塑和心血管事件的影响. 中华心血管病杂志, 2004, 32(10): 892.
27. 石翔. 不同剂量美托洛尔治疗慢性充血性心力衰竭的疗效及耐受性比较观察. 疑难病杂志, 2005, 4(1): 7-9.
28. 王莉. 不同剂量美托洛尔治疗慢性充血性心力衰竭的临床疗效观察. 现代医药卫生, 2005, 21(17): 2289-2290.
29. 邹剑杰, 李永超, 张勇. 美托洛尔治疗慢性重度心力衰竭患者的耐受剂量范围和安全性研究. 四川省卫生管理干部学院学报, 2005, 24(2): 88-89.
30. Gottlieb S, Fisher ML, Kjekshus J, on behalf of the MERIT-HF Investigators. Tolerability of beta-blocker initiation and titration in the Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure (MERIT-HF). Circulation, 2002, 105: 1182-1188.
31. Macdonald PS, Keogh AM, Aboyoun CL, et al. Tolerability and efficacy of carvedilol in patients with New York Heart Association class IV heart failure. J Am Coll Cardiol, 1999, 33: 924-931.
32. Waagstein F, Bristow MR, Swedberg K, et al. Beneficial effects of metoprolol in idiopathic dilated cardiomyopathy. Lancet, 1993, 342: 1441-1446.
33. Engelmeier RS, O’Connell JB, Walsh R, et al. Improvement in symptoms and exercise tolerance by metoprolol in patients with dilated cardiomyopathy: a double-blind, randomized, placebo-controlled trial. Circulation, 1985, 72: 536-546.
34. Fisher ML, Gottlieb SS, Plotnick GD, et al. Beneficial effects of metoprolol in heart failure associated with coronary artery disease: a randomized trial. J Am Coll Cardiol, 1994, 23: 943–950.
35. Eichhorn EJ, Heesch CM, Barnett JH, et al. Effect of metoprolol on myocardial function and energetics in patients with nonischemic dilated cardiomyopathy: a randomized, double-blind, placebo-controlled study. J Am Coll Cardiol, 1994, 24: 1310–1320.
36. ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation, 2001, 11, 104(24): 2996-3007.
37. Remme WJ, Swedberg K, Task Force for the Diagnosis and Treatment of Chronic Heart Failure, European Society of Cardiology. Guidelines for the diagnosis and treatment of chronic heart failure. Eur Heart J, 2001, 22(17): 1527-1560.
38. Poole-Wilson PA, Swedberg K, Cleland JG, et al. Comparison of carvedilol and metoprolol on clinical outcomes in patients with chronic heart failure in the Carvedilol Or Metoprolol European Trial (COMET): randomised controlled trial. Lancet, 2003, 362: 7-13.

Chinese Journal of Evidence-Based Medicine

Efficacy and Safety of Different Doses of Metoprolol for Patients with Chronic Heart Failure

Abstract Full text Figures/Tables Video References Cited by

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