Di Lenarda Andrea, Remme Willem J, Charlesworth Andrew, Cleland John G F, Lutiger Beatrix, Metra Marco, Komajda Michel, Torp-Pedersen Christian, Scherhag Armin, Swedberg Karl, Poole-Wilson Philip A
Department of Cardiology, Ospedale di Cattinara, Strada di Fiume 447, 34100 Trieste, Italy.
Eur J Heart Fail. 2005 Jun;7(4):640-9. doi: 10.1016/j.ejheart.2004.09.010.
The Carvedilol or Metoprolol European Trial (COMET) reported a significant survival benefit for carvedilol, a beta1-, beta2- and alpha1-blocker, vs. metoprolol tartrate, a beta1-selective blocker, in patients with mild-to-severe chronic heart failure (CHF). Patients on treatment with metoprolol might benefit from switching to carvedilol.
To investigate the safety and tolerability of switching beta-blockers in CHF.
At the end of COMET, the Steering Committee recommended that study medication was stopped without unblinding, and patients were commenced on open-label beta-blockade at a dose equivalent to half the dose of blinded therapy, with subsequent titration to target or maximum tolerated dose. Patients were followed for 30 days.
1321 out of 1440 patients were transitioned to open-label treatment (76.8% to carvedilol). Serious adverse and CHF-related events were respectively 9.4% and 4.7% in those switching from carvedilol to metoprolol and 3.1% and 1.5% in patients switching from metoprolol to carvedilol. Patients who switched from carvedilol to metoprolol showed the highest mortality or hospitalisation rate (12.3%) in comparison with those who switched from metoprolol to carvedilol (3.1%, p<0.001) or who stayed on the same drug (carvedilol: 2.5%, p<0.001; metoprolol: 4.2%, p=0.04). Reducing the initial dose of the second beta-blocker maximised the safety of this strategy. Event rate was higher in patients with more severe heart failure and in those withdrawing from beta-blockade.
Our data show that switching beta-blockers is a practical, safe and well-tolerated strategy to optimise treatment of CHF. Patients who switched to carvedilol showed the lowest rate of adverse events. A closer clinical monitoring is recommended during transition in high-risk patients.
卡维地洛或美托洛尔欧洲试验(COMET)报告称,对于轻至重度慢性心力衰竭(CHF)患者,β1、β2和α1受体阻滞剂卡维地洛相较于β1选择性阻滞剂酒石酸美托洛尔具有显著的生存获益。接受美托洛尔治疗的患者可能会从换用卡维地洛中获益。
研究在CHF患者中更换β受体阻滞剂的安全性和耐受性。
在COMET试验结束时,指导委员会建议在不解盲的情况下停止研究用药,患者开始接受开放标签的β受体阻滞剂治疗,剂量相当于盲法治疗剂量的一半,随后滴定至目标剂量或最大耐受剂量。对患者进行了30天的随访。
1440例患者中有1321例转为开放标签治疗(76.8%转为卡维地洛)。从卡维地洛换用美托洛尔的患者中,严重不良事件和CHF相关事件分别为9.4%和4.7%,而从美托洛尔换用卡维地洛的患者中分别为3.1%和1.5%。与从美托洛尔换用卡维地洛的患者(3.1%,p<0.001)或继续使用同一种药物的患者(卡维地洛:2.5%,p<0.001;美托洛尔:4.2%,p=0.04)相比,从卡维地洛换用美托洛尔的患者的死亡率或住院率最高(12.3%)。降低第二种β受体阻滞剂的初始剂量可使该策略的安全性最大化。心力衰竭更严重的患者以及停用β受体阻滞剂的患者的事件发生率更高。
我们的数据表明,更换β受体阻滞剂是优化CHF治疗的一种实用、安全且耐受性良好的策略。换用卡维地洛的患者不良事件发生率最低。建议在高危患者转换治疗期间进行更密切的临床监测。