周焱 1 , 楊茗 1 , 陳滔 2 , 董碧蓉 1
  • 1.四川大學(xué)華西醫(yī)院老年科(成都610041)2.西南財(cái)經(jīng)大學(xué)保險(xiǎn)學(xué)院(成都 610071);

目的 　評(píng)價(jià)不同劑量美托洛爾治療慢性心衰的有效性與安全性。
方法 　計(jì)算機(jī)檢索MEDLINE、EMbase、Cochrane圖書(shū)館、CMB、CMCC、萬(wàn)方數(shù)據(jù)庫(kù)和相關(guān)網(wǎng)站，檢索日期截至2006年3月，篩選有關(guān)美托洛爾治療慢性心力衰竭的系統(tǒng)評(píng)價(jià)、隨機(jī)對(duì)照試驗(yàn)及現(xiàn)行指南等。對(duì)所獲文獻(xiàn)進(jìn)行質(zhì)量評(píng)價(jià)。比較大劑量（100 mg/d）和小劑量（ lt;100 mg/d）美托洛爾的有效性與安全性。
結(jié)果 　1個(gè)小樣本短期隨訪的隨機(jī)對(duì)照試驗(yàn)發(fā)現(xiàn)，美托洛爾100 mg/d 比25 mg/d和50 mg/d 能更好地改善慢性心功能不全。MERIT-HF的亞組分析支持根據(jù)患者的耐受性和心率制定個(gè)體化的劑量滴定方案。目前的指南推薦使用美托洛爾緩釋/控釋片直至最大耐受劑量或200 mg/d的目標(biāo)劑量。美托洛爾緩釋/控釋片治療慢性心功能不全的耐受性較好，大劑量美托洛爾的耐受性可能比小劑量稍差，但長(zhǎng)期使用利大于弊。沒(méi)有發(fā)現(xiàn)耐受性存在人種差異,也未發(fā)現(xiàn)不良反應(yīng)與劑量的關(guān)系。
結(jié)論 　現(xiàn)有證據(jù)無(wú)法提供美托洛爾治療慢性心功能不全的最佳劑量，但美托洛爾緩釋/控釋片以200 mg/d為目標(biāo)劑量安全有效。不良反應(yīng)的發(fā)生是否與劑量有關(guān)尚不能得出確切結(jié)論。

引用本文： 周焱,楊茗,陳滔,董碧蓉. 不同劑量美托洛爾治療慢性心力衰竭的有效性及安全性評(píng)價(jià). 中國(guó)循證醫(yī)學(xué)雜志, 2007, 07(6): 472-477. doi: 復(fù)制

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. 中華醫(yī)學(xué)會(huì)心血管病分會(huì), 中華心血管病雜志編輯委員會(huì). 慢性收縮性心力衰竭治療建議. 中華心血管病雜志, 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. 余強(qiáng), 李德旺, 蒲世玉. 不同劑量美托洛爾治療充血性心力衰竭療效觀察. 臨床心血管病雜志, 1997, 13(6): 367.
23. 劉小珍, 劉遠(yuǎn)勝. 倍他樂(lè)克治療39例甲亢性心臟病并心衰的療效分析. 現(xiàn)代診斷與治療, 2003, 14(3): 149.
24. 朱宣德. 不同劑量倍他樂(lè)克治療舒張性心力衰竭的療效觀察.中國(guó)綜合臨床, 2004, 20(11): 970-972.
25. 高志廣, 杜玉芝, 任國(guó)成. 不同劑量酒石酸美托洛爾治療慢性心力衰竭的對(duì)比研究. 中國(guó)藥物與臨床, 2005, 5(1): 63-64.
26. 李振魁, 梅霞, 祝善俊, 等. 不同劑量美托洛爾對(duì)慢性心力衰竭患者心室重塑和心血管事件的影響. 中華心血管病雜志, 2004, 32(10): 892.
27. 石翔. 不同劑量美托洛爾治療慢性充血性心力衰竭的療效及耐受性比較觀察. 疑難病雜志, 2005, 4(1): 7-9.
28. 王莉. 不同劑量美托洛爾治療慢性充血性心力衰竭的臨床療效觀察. 現(xiàn)代醫(yī)藥衛(wèi)生, 2005, 21(17): 2289-2290.
29. 鄒劍杰, 李永超, 張勇. 美托洛爾治療慢性重度心力衰竭患者的耐受劑量范圍和安全性研究. 四川省衛(wèi)生管理干部學(xué)院學(xué)報(bào), 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. 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. 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. 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. 4. Zhu XD. Effects of different doses of betaloc on diastolic heart failure. Clinical Medicine of China, 2004, 20(11): 970-972.
  5. 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. 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. 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. 8. Wang L. Clinical observation of different doses of metoprolol for chronic heart failure. Modern Medicine & Health, 2005,21(17)：2289-2290.
  9. 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. 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. 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. 12. Institute for Clinical Systems Improvement (ICSI). Inpatient management of heart failure. Bloomington (MN): Institute for Clinical Systems Improvement (ICSI); 2004 Feb. 85.
  13. 13. 中華醫(yī)學(xué)會(huì)心血管病分會(huì), 中華心血管病雜志編輯委員會(huì). 慢性收縮性心力衰竭治療建議. 中華心血管病雜志, 2002, 30(1): 7-23.
  14. 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. 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. 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. 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. 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. 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. 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. 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. 22. 余強(qiáng), 李德旺, 蒲世玉. 不同劑量美托洛爾治療充血性心力衰竭療效觀察. 臨床心血管病雜志, 1997, 13(6): 367.
  23. 23. 劉小珍, 劉遠(yuǎn)勝. 倍他樂(lè)克治療39例甲亢性心臟病并心衰的療效分析. 現(xiàn)代診斷與治療, 2003, 14(3): 149.
  24. 24. 朱宣德. 不同劑量倍他樂(lè)克治療舒張性心力衰竭的療效觀察.中國(guó)綜合臨床, 2004, 20(11): 970-972.
  25. 25. 高志廣, 杜玉芝, 任國(guó)成. 不同劑量酒石酸美托洛爾治療慢性心力衰竭的對(duì)比研究. 中國(guó)藥物與臨床, 2005, 5(1): 63-64.
  26. 26. 李振魁, 梅霞, 祝善俊, 等. 不同劑量美托洛爾對(duì)慢性心力衰竭患者心室重塑和心血管事件的影響. 中華心血管病雜志, 2004, 32(10): 892.
  27. 27. 石翔. 不同劑量美托洛爾治療慢性充血性心力衰竭的療效及耐受性比較觀察. 疑難病雜志, 2005, 4(1): 7-9.
  28. 28. 王莉. 不同劑量美托洛爾治療慢性充血性心力衰竭的臨床療效觀察. 現(xiàn)代醫(yī)藥衛(wèi)生, 2005, 21(17): 2289-2290.
  29. 29. 鄒劍杰, 李永超, 張勇. 美托洛爾治療慢性重度心力衰竭患者的耐受劑量范圍和安全性研究. 四川省衛(wèi)生管理干部學(xué)院學(xué)報(bào), 2005, 24(2): 88-89.
  30. 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. 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. 32. Waagstein F, Bristow MR, Swedberg K, et al. Beneficial effects of metoprolol in idiopathic dilated cardiomyopathy. Lancet, 1993, 342: 1441-1446.
  33. 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. 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. 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. 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. 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. 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.