坎地沙坦对心力衰竭患者非致死性心肌梗死和心血管死亡的影响。

Impact of candesartan on nonfatal myocardial infarction and cardiovascular death in patients with heart failure.

作者信息

Demers Catherine, McMurray John J V, Swedberg Karl, Pfeffer Marc A, Granger Christopher B, Olofsson Bertil, McKelvie Robert S, Ostergren Jan, Michelson Eric L, Johansson Peter A, Wang Duolao, Yusuf Salim

机构信息

McMaster University, Hamilton, Ontario, Canada.

出版信息

JAMA. 2005 Oct 12;294(14):1794-8. doi: 10.1001/jama.294.14.1794.

DOI:10.1001/jama.294.14.1794

PMID:16219883

Abstract

CONTEXT

Angiotensin-converting enzyme (ACE) inhibitors reduce the risk of myocardial infarction (MI), but it is not known whether angiotensin receptor blockers have the same effect.

OBJECTIVE

To assess the impact of the angiotensin receptor blocker candesartan on MI and other coronary events in patients with heart failure.

DESIGN, SETTING, AND PARTICIPANTS: The Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) program, a randomized, placebo-controlled study enrolling patients (mean age, 66 [SD, 11] years) with New York Heart Association class II to IV symptoms who were randomly allocated to receive candesartan (target dose, 32 mg once daily) or matching placebo given in addition to optimal therapy for heart failure. Patients were enrolled from March 1999 through March 2001. Of 7599 patients allocated, 4004 (53%) had experienced a previous MI, and 1808 (24%) currently had angina. At baseline, 3125 (41%) were receiving an ACE inhibitor; 4203 (55%), a beta-blocker; 3153 (42%), a lipid-lowering drug; 4246 (56%), aspirin; and 6286 (83%), a diuretic.

MAIN OUTCOME MEASURE

The primary outcome of the present analysis was the composite of cardiovascular death or nonfatal MI in patients with heart failure receiving candesartan or placebo.

RESULTS

During the median follow-up of 37.7 months, the primary outcome of cardiovascular death or nonfatal MI was significantly reduced in the candesartan group (775 patients [20.4%]) vs the placebo group (868 [22.9%]) (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.79-0.96; P = .004; number needed to treat [NNT], 40). Nonfatal MI alone was also significantly reduced in the candesartan group (116 [3.1%]) vs the placebo group (148 [3.9%]) (HR, 0.77; 95% CI, 0.60-0.98; P = .03; NNT, 118). The secondary outcome of fatal MI, sudden death, or nonfatal MI was significantly reduced with candesartan (459 [12.1%]) vs placebo (522 [13.8%]) (HR, 0.86; 95% CI, 0.75-0.97; P = .02; NNT, 59). Risk reductions in cardiovascular death or nonfatal MI were similar across predetermined subgroups and the component CHARM trials. There was no impact on hospitalizations for unstable angina or coronary revascularization procedures with candesartan.

CONCLUSION

In patients with heart failure, candesartan significantly reduces the risk of the composite outcome of cardiovascular death or nonfatal MI.

摘要

背景

血管紧张素转换酶（ACE）抑制剂可降低心肌梗死（MI）风险，但血管紧张素受体阻滞剂是否具有同样效果尚不清楚。

目的

评估血管紧张素受体阻滞剂坎地沙坦对心力衰竭患者发生MI及其他冠状动脉事件的影响。

设计、设置与参与者：心力衰竭中坎地沙坦：死亡率和发病率降低评估（CHARM）项目，一项随机、安慰剂对照研究，纳入纽约心脏协会II至IV级症状的患者（平均年龄66[标准差，11]岁），这些患者被随机分配接受坎地沙坦（目标剂量，每日一次32mg）或匹配的安慰剂，同时给予心力衰竭的最佳治疗。患者于1999年3月至2001年3月入组。在7599例分配的患者中，4004例（53%）曾发生过MI，1808例（24%）目前患有心绞痛。基线时，3125例（41%）正在接受ACE抑制剂治疗；4203例（55%）接受β受体阻滞剂治疗；3153例（42%）接受降脂药物治疗；4246例（56%）接受阿司匹林治疗；6286例（83%）接受利尿剂治疗。

主要结局指标

本分析的主要结局是接受坎地沙坦或安慰剂的心力衰竭患者发生心血管死亡或非致死性MI的复合结局。

结果

在37.7个月的中位随访期内，坎地沙坦组（775例患者[20.4%]）发生心血管死亡或非致死性MI的主要结局显著低于安慰剂组（868例[22.9%]）（风险比[HR]，0.87；95%置信区间[CI]，0.79 - 0.96；P = 0.004；需治疗人数[NNT]，40）。坎地沙坦组单独发生非致死性MI的情况也显著低于安慰剂组（116例[3.1%]）（148例[3.9%]）（HR，0.77；95% CI，0.60 - 0.98；P = 0.03；NNT，118）。坎地沙坦组致死性MI、心源性猝死或非致死性MI的次要结局显著低于安慰剂组（459例[12.1%]）（522例[13.8%]）（HR，0.86；95% CI，0.75 - 0.97；P = 0.02；NNT，59）。在预先确定的亚组和CHARM试验的各个组成部分中，心血管死亡或非致死性MI的风险降低情况相似。坎地沙坦对不稳定型心绞痛住院或冠状动脉血运重建手术没有影响。