坎地沙坦对慢性心力衰竭患者死亡率和发病率的影响：CHARM总体研究项目

Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme.

作者信息

Pfeffer Marc A, Swedberg Karl, Granger Christopher B, Held Peter, McMurray John J V, Michelson Eric L, Olofsson Bertil, Ostergren Jan, Yusuf Salim, Pocock Stuart

机构信息

Cardiovascular Division, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA.

出版信息

Lancet. 2003 Sep 6;362(9386):759-66. doi: 10.1016/s0140-6736(03)14282-1.

DOI:10.1016/s0140-6736(03)14282-1

PMID:13678868

Abstract

BACKGROUND

Patients with chronic heart failure (CHF) are at high risk of cardiovascular death and recurrent hospital admissions. We aimed to find out whether the use of an angiotensin-receptor blocker could reduce mortality and morbidity.

METHODS

In parallel, randomised, double-blind, controlled, clinical trials we compared candesartan with placebo in three distinct populations. We studied patients with left-ventricular ejection fraction (LVEF) 40% or less who were not receiving angiotensin-converting-enzyme inhibitors because of previous intolerance or who were currently receiving angiotensin-converting-enzyme inhibitors, and patients with LVEF higher than 40%. Overall, 7601 patients (7599 with data) were randomly assigned candesartan (n=3803, titrated to 32 mg once daily) or matching placebo (n=3796), and followed up for at least 2 years. The primary outcome of the overall programme was all-cause mortality, and for all the component trials was cardiovascular death or hospital admission for CHF. Analysis was by intention to treat.

FINDINGS

Median follow-up was 37.7 months. 886 (23%) patients in the candesartan and 945 (25%) in the placebo group died (unadjusted hazard ratio 0.91 [95% CI 0.83-1.00], p=0.055; covariate adjusted 0.90 [0.82-0.99], p=0.032), with fewer cardiovascular deaths (691 [18%] vs 769 [20%], unadjusted 0.88 [0.79-0.97], p=0.012; covariate adjusted 0.87 [0.78-0.96], p=0.006) and hospital admissions for CHF (757 [20%] vs 918 [24%], p<0.0001) in the candesartan group. There was no significant heterogeneity for candesartan results across the component trials. More patients discontinued candesartan than placebo because of concerns about renal function, hypotension, and hyperkalaemia.

INTERPRETATION

Candesartan was generally well tolerated and significantly reduced cardiovascular deaths and hospital admissions for heart failure. Ejection fraction or treatment at baseline did not alter these effects.

摘要

背景

慢性心力衰竭（CHF）患者心血管死亡和再次住院风险很高。我们旨在查明使用血管紧张素受体阻滞剂是否能降低死亡率和发病率。

方法

在平行、随机、双盲、对照临床试验中，我们在三个不同人群中将坎地沙坦与安慰剂进行了比较。我们研究了左心室射血分数（LVEF）为40%或更低、因既往不耐受未接受血管紧张素转换酶抑制剂或当前正在接受血管紧张素转换酶抑制剂的患者，以及LVEF高于40%的患者。总体而言，7601例患者（7599例有数据）被随机分配接受坎地沙坦（n = 3803，滴定至每日一次32 mg）或匹配的安慰剂（n = 3796），并随访至少2年。整个项目的主要结局是全因死亡率，所有组成试验的主要结局是心血管死亡或因CHF住院。分析采用意向性治疗。

结果

中位随访时间为37.7个月。坎地沙坦组886例（23%）患者和安慰剂组945例（25%）患者死亡（未调整风险比0.91 [95% CI 0.83 - 1.00]，p = 0.055；协变量调整后0.90 [0.82 - 0.99]，p = 0.032），坎地沙坦组心血管死亡（691例[18%]对769例[20%]，未调整0.88 [0.79 - 0.97]，p = 0.012；协变量调整后0.87 [0.78 - 0.96]，p = 0.006）和因CHF住院（757例[20%]对918例[24%]，p < 0.0001）更少。各组成试验中坎地沙坦的结果无显著异质性。因担心肾功能、低血压和高钾血症，停用坎地沙坦的患者比停用安慰剂的患者更多。