Sturm B, Pacher R, Strametz-Juranek J, Berger R, Frey B, Stanek B
Department of Cardiology, University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria.
Eur J Heart Fail. 2000 Dec;2(4):407-12. doi: 10.1016/s1388-9842(00)00120-3.
The survival benefit of beta-blocker treatment in patients with heart failure has been established in recent trials. Yet, the impact of beta-blockers added on high dose angiotensin converting enzyme inhibitors has not been reported.
To investigate the effect of atenolol, a hydrophilic, selective beta1-adrenergic antagonist, added on enalapril 40 mg/day in patients with advanced left ventricular dysfunction in a double-blind placebo-controlled trial.
One hundred and nineteen patients with class II or III heart failure, left ventricular ejection fraction < or = 25% and treatment with 40 mg enalapril daily were given an initial challenge dose of atenolol 12. 5 mg. One hundred patients (54 with idiopathic, 28 with ischemic, 18 with other dilated cardiomyopathy) tolerated challenge and were randomized to atenolol (maintenance dose 89+/-11 mg/day, range 50-100 mg/day) or placebo. The primary endpoint was combined worsening heart failure or death within 2 years, the secondary endpoint was hospitalization for cardiac events.
After 395+/-266 days interim analysis revealed a significant difference between the atenolol and placebo group (log rank P<0.01) and the trial was concluded. Twenty-seven patients had developed worsening heart failure (8 in the atenolol group vs. 19 in the placebo group) and 13 patients had died (5 in the atenolol vs. 8 in the placebo group). Overall there were 23 hospitalizations for cardiac events (6 in the atenolol group vs. 21 in the placebo group, P=0.07); 17 hospitalizations were due to worsening heart failure (5 in the atenolol group, 12 in the placebo-group, P=0.05) and 10 due to arrhythmias (1 in the atenolol group vs. 9 in the placebo group, P<0.01)
The data suggest that in patients with advanced left ventricular dysfunction, beta-blockers can provide substantial benefits supplementary to that already achieved with high dose enalapril treatment.
近期试验已证实β受体阻滞剂治疗对心力衰竭患者的生存益处。然而，关于在高剂量血管紧张素转换酶抑制剂基础上加用β受体阻滞剂的影响尚未见报道。
在一项双盲安慰剂对照试验中，研究亲水性选择性β1肾上腺素能拮抗剂阿替洛尔加用至每日40毫克依那普利对晚期左心室功能不全患者的影响。
119例Ⅱ级或Ⅲ级心力衰竭、左心室射血分数≤25%且每日接受40毫克依那普利治疗的患者，给予初始冲击剂量阿替洛尔12.5毫克。100例患者（54例特发性、28例缺血性、18例其他扩张型心肌病）耐受冲击并被随机分为阿替洛尔组（维持剂量89±11毫克/天，范围50 - 100毫克/天）或安慰剂组。主要终点为2年内心力衰竭恶化或死亡的复合终点，次要终点为因心脏事件住院。
经过395±266天的中期分析显示，阿替洛尔组与安慰剂组之间存在显著差异（对数秩检验P<0.01），试验结束。27例患者出现心力衰竭恶化（阿替洛尔组8例，安慰剂组19例），13例患者死亡（阿替洛尔组5例，安慰剂组8例）。总体上有23次因心脏事件住院（阿替洛尔组6次，安慰剂组21次，P = 0.07）；17次住院是由于心力衰竭恶化（阿替洛尔组5次，安慰剂组12次，P = 0.05），10次是由于心律失常（阿替洛尔组1次，安慰剂组9次，P<0.01）。
数据表明，对于晚期左心室功能不全患者，β受体阻滞剂在高剂量依那普利治疗已取得的效果基础上可提供显著的额外益处。
