Packer M, Colucci W S, Sackner-Bernstein J D, Liang C S, Goldscher D A, Freeman I, Kukin M L, Kinhal V, Udelson J E, Klapholz M, Gottlieb S S, Pearle D, Cody R J, Gregory J J, Kantrowitz N E, LeJemtel T H, Young S T, Lukas M A, Shusterman N H
College of Physicians and Surgeons, Columbia University, New York, NY, USA.
Circulation. 1996 Dec 1;94(11):2793-9. doi: 10.1161/01.cir.94.11.2793.
Carvedilol has improved the symptomatic status of patients with moderate to severe heart failure in single-center studies, but its clinical effects have not been evaluated in large, multicenter trials.
We enrolled 278 patients with moderate to severe heart failure (6-minute walk distance, 150 to 450 m) and a left ventricular ejection fraction < or = 0.35 at 31 centers. After an open-label, run-in period, each patient was randomly assigned (double-blind) to either placebo (n = 145) or carvedilol (n = 133; target dose, 25 to 50 mg BID) for 6 months, while background therapy with digoxin, diuretics, and an ACE inhibitor remained constant. Compared with placebo, patients in the carvedilol group had a greater frequency of symptomatic improvement and lower risk of clinical deterioration, as evaluated by changes in the NYHA functional class (P = .014) or by a global assessment of progress judged either by the patient (P = .002) or by the physician (P < .001). In addition, treatment with carvedilol was associated with a significant increase in ejection fraction (P < .001) and a significant decrease in the combined risk of morbidity and mortality (P = .029). In contrast, carvedilol therapy had little effect on indirect measures of patient benefit, including changes in exercise tolerance or quality-of-life scores. The effects of the drug were similar in patients with ischemic heart disease or idiopathic dilated cardiomyopathy as the cause of heart failure.
These findings indicate that, in addition to its favorable effects on survival, carvedilol produces important clinical benefits in patients with moderate to severe heart failure treated with digoxin, diuretics, and an ACE inhibitor.
在单中心研究中，卡维地洛已改善了中重度心力衰竭患者的症状状态，但尚未在大型多中心试验中评估其临床效果。
我们在31个中心纳入了278例中重度心力衰竭患者（6分钟步行距离为150至450米），左心室射血分数≤0.35。经过开放标签的导入期后，每位患者被随机（双盲）分配至安慰剂组（n = 145）或卡维地洛组（n = 133；目标剂量为每日两次25至50毫克），为期6个月，同时地高辛、利尿剂和ACE抑制剂的背景治疗保持不变。与安慰剂相比，根据纽约心脏协会（NYHA）功能分级的变化（P = 0.014）或患者（P = 0.002）或医生（P < 0.001）判断的总体病情进展评估，卡维地洛组患者症状改善的频率更高，临床恶化的风险更低。此外，卡维地洛治疗与射血分数显著增加（P < 0.001）以及发病和死亡综合风险显著降低（P = 0.029）相关。相比之下，卡维地洛治疗对患者获益的间接指标影响较小，包括运动耐量或生活质量评分的变化。该药物对因缺血性心脏病或特发性扩张型心肌病导致心力衰竭的患者效果相似。
这些发现表明，除了对生存有有利影响外，卡维地洛在接受地高辛、利尿剂和ACE抑制剂治疗的中重度心力衰竭患者中产生了重要的临床益处。
