不同剂量美托洛尔治疗慢性心力衰竭的有效性及安全性评价

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

目的评价不同剂量美托洛尔治疗慢性心衰的有效性与安全性。方法计算机检索MEDLINE、EMbase、Cochrane图书馆、CMB、CMCC、万方数据库和相关网站,检索日期截至2006年3月,筛选有关美托洛尔治疗慢性心力衰竭的系统评价、随机对照试验及现行指南等。对所获文献进行质量评价。比较大剂量(100mg/d)和小剂量(<100mg/d)美托洛尔的有效性与安全性。结果1个小样本短期随访的随机对照试验发现,美托洛尔100mg/d比25mg/d和50mg/d能更好地改善慢性心功能不全。MERIT-HF的亚组分析支持根据患者的耐受性和心率制定个体化的剂量滴定方案。目前的指南推荐使用美托洛尔缓释/控释片直至最大耐受剂量或200mg/d的目标剂量。美托洛尔缓释/控释片治疗慢性心功能不全的耐受性较好,大剂量美托洛尔的耐受性可能比小剂量稍差,但长期使用利大于弊。没有发现耐受性存在人种差异,也未发现不良反应与剂量的关系。结论现有证据无法提供美托洛尔治疗慢性心功能不全的最佳剂量,但美托洛尔缓释/控释片以200mg/d为目标剂量安全有效。不良反应的发生是否与剂量有关尚不能得出确切结论。

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 （〈100 mg/d） were compared. Results Only one small-scale, shortterm 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 highdose 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.