Krum H, Sackner-Bernstein J D, Goldsmith R L, Kukin M L, Schwartz B, Penn J, Medina N, Yushak M, Horn E, Katz S D
Division of Circulatory Physiology, Columbia University, College of Physicians and Surgeons, New York, NY, USA.
Circulation. 1995 Sep 15;92(6):1499-506. doi: 10.1161/01.cir.92.6.1499.
Clinical trials have shown that beta-adrenergic blocking drugs are effective and well tolerated in patients with mild to moderate heart failure, but the utility and safety of these drugs in patients with advanced disease have not been evaluated.
We enrolled 56 patients with severe chronic heart failure into a double-blind, placebo-controlled study of the vasodilating beta-blocker carvedilol. All patients had advanced heart failure, as evidenced by a mean left ventricular ejection fraction of 0.16 +/- 0.01 and a mean maximal oxygen consumption of 13.6 +/- 0.6 mL.kg-1.min-1 despite digitalis, diuretics, and an angiotensin-converting enzyme inhibitor (if tolerated). After a 3-week, open-label, up-titration period, 49 of the 56 patients were assigned (in a double-blind fashion using a 2:1 randomization) to receive either carvedilol (25 mg BID, n = 33) or matching placebo (n = 16) for 14 weeks, while background therapy remained constant. Hemodynamic and functional variables were measured at the start and end of the study. Compared with the placebo group, patients in the carvedilol group showed improved cardiac performance, as reflected by an increase in left ventricular ejection fraction (P = .005) and stroke volume index (P = .010) and a decrease in pulmonary wedge pressure, mean right atrial pressure, and systemic vascular resistance (P = .003, .002, and .017, respectively). In addition, compared with placebo, patients treated with carvedilol benefited clinically, as shown by an improvement in symptom scores (P = .002), functional class (P = .013), and submaximal exercise tolerance (P = .006). The combined risk of death, worsening heart failure, and life-threatening ventricular tachyarrhythmia was lower in the carvedilol group than in the placebo group (P = .028), but carvedilol-treated patients had more dizziness and advanced heart block.
Carvedilol produces clinical and hemodynamic improvement in patients who have severe heart failure despite treatment with angiotensin-converting enzyme inhibitors.
临床试验表明，β-肾上腺素能阻滞剂对轻至中度心力衰竭患者有效且耐受性良好，但这些药物在晚期心力衰竭患者中的效用和安全性尚未得到评估。
我们将56例重度慢性心力衰竭患者纳入一项关于血管扩张性β受体阻滞剂卡维地洛的双盲、安慰剂对照研究。所有患者均患有晚期心力衰竭，尽管使用了洋地黄、利尿剂和血管紧张素转换酶抑制剂（若耐受），但其平均左心室射血分数仍为0.16±0.01，平均最大耗氧量为13.6±0.6 mL·kg-1·min-1。在为期3周的开放标签、剂量递增期后，56例患者中的49例（采用2:1随机分组的双盲方式）被分配接受卡维地洛（25 mg，每日两次，n = 33）或匹配的安慰剂（n = 16）治疗14周，同时背景治疗保持不变。在研究开始和结束时测量血流动力学和功能变量。与安慰剂组相比，卡维地洛组患者的心脏功能有所改善，表现为左心室射血分数增加（P = 0.005）、每搏量指数增加（P = 0.010）以及肺楔压、平均右心房压和体循环血管阻力降低（分别为P = 0.003、0.002和0.017）。此外，与安慰剂相比，接受卡维地洛治疗的患者在临床方面也有所获益，症状评分改善（P = 0.002）、心功能分级改善（P = 0.013）以及次极量运动耐量改善（P = 0.006）。卡维地洛组死亡、心力衰竭恶化和危及生命的室性快速心律失常的综合风险低于安慰剂组（P = 0.028），但接受卡维地洛治疗的患者头晕和高度房室传导阻滞的情况更多。
尽管使用了血管紧张素转换酶抑制剂治疗，卡维地洛仍能使重度心力衰竭患者的临床症状和血流动力学得到改善。
