Clark Andrew L, Coats Andrew J S, Krum Henry, Katus Hugo A, Mohacsi Paul, Salekin Damien, Schultz Melissa K, Packer Milton, Anker Stefan D
Department of Cardiology, University of Hull, UK.
Monash University, Melbourne, VIC, Australia.
J Cachexia Sarcopenia Muscle. 2017 Aug;8(4):549-556. doi: 10.1002/jcsm.12191. Epub 2017 Feb 27.
Cardiac cachexia frequently accompanies the progression of heart failure despite the use of effective therapies for left ventricular dysfunction. Activation of the sympathetic nervous system has been implicated in the pathogenesis of weight loss, but the effects of sympathetic antagonism on cachexia are not well defined.
We prospectively evaluated changes in body weight in 2289 patients with heart failure who had dyspnoea at rest or on minimal exertion and a left ventricular ejection fraction <25%. Patients were randomly assigned (double-blind) to receive either placebo (n = 1133) or carvedilol (n = 1156) and were followed for the occurrence of major clinical events for up to 29 months (COPERNICUS trial). Patients were not enrolled if they had signs of clinically significant fluid retention due to heart failure.
Patients in the carvedilol group were 33% less likely than patients in the placebo group to experience a further significant loss of weight (>6%) (95% confidence interval: 14-48%, P = 0.002) and were 37% more likely to experience a significant gain in weight (≥5%) (95% confidence interval: 12-66%, P = 0.002). Carvedilol's ability to prevent weight loss was most marked in patients with increased body mass index at baseline, whereas its ability to promote weight gain was most marked in patients with decreased body mass index at baseline. Increases in weight were not accompanied by evidence of fluid retention. Baseline values for body mass index and change in body weight were significant predictors of survival regardless of treatment.
Carvedilol attenuated the development and promoted a partial reversal of cachexia in patients with severe chronic heart failure, supporting a role for prolonged sympathetic activation in the genesis of weight loss.
尽管针对左心室功能障碍采用了有效的治疗方法，但心脏恶病质仍常伴随心力衰竭的进展。交感神经系统的激活与体重减轻的发病机制有关，但交感神经拮抗对恶病质的影响尚不明确。
我们前瞻性评估了2289例静息或轻微活动时出现呼吸困难且左心室射血分数<25%的心力衰竭患者的体重变化。患者被随机（双盲）分配接受安慰剂（n = 1133）或卡维地洛（n = 1156），并随访长达29个月的主要临床事件发生情况（COPERNICUS试验）。如果患者因心力衰竭出现具有临床意义的液体潴留体征，则不纳入研究。
卡维地洛组患者体重进一步显著下降（>6%）的可能性比安慰剂组患者低33%（95%置信区间：14 - 48%，P = 0.002），体重显著增加（≥5%）的可能性比安慰剂组患者高37%（95%置信区间：12 - 66%，P = 0.002）。卡维地洛预防体重减轻的能力在基线体重指数增加的患者中最为明显，而其促进体重增加的能力在基线体重指数降低的患者中最为明显。体重增加并未伴有液体潴留的证据。无论治疗如何，体重指数的基线值和体重变化都是生存的重要预测因素。
卡维地洛减轻了重度慢性心力衰竭患者恶病质的发展并促进了部分逆转，支持长期交感神经激活在体重减轻发生中的作用。
