Effect of Aliskiren on Postdischarge Mortality and Heart Failure Readmissions Among Patients Hospitalized for Heart Failure The ASTRONAUT Randomized Trial
Effect of Aliskiren on Postdischarge Mortality and Heart Failure Readmissions Among Patients Hospitalized for Heart Failure The ASTRONAUT Randomized Trial
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DOI：
10.1001/jama.2013.1954
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发表时间：
2013-03-20
影响因子：
120.7
通讯作者：
Maggioni, Aldo P.
中科院分区：
文献类型：
--
作者：
Gheorghiade, Mihai;Boehm, Michael;Maggioni, Aldo P.
心力衰竭住院（HHF）是一项重大的健康负担，出院后早期再住院和死亡率较高。
目的：研究在标准治疗基础上加用直接肾素抑制剂阿利吉仑是否会降低心力衰竭住院患者心血管（CV）死亡或心力衰竭再住院的发生率。
设计、地点和参与者：国际性、双盲、安慰剂对照研究，在入院后中位数5天对血流动力学稳定的心力衰竭住院患者进行随机分组。符合条件的患者为18岁及以上，左心室射血分数（LVEF）≤40%，利钠肽升高（脑利钠肽[BNP]≥400 pg/mL或N - 末端前体BNP[NT - proBNP]≥1600 pg/mL），并有液体超负荷的体征和症状。患者于2009年5月至2011年12月从北美洲、南美洲、欧洲和亚洲的316个地点招募。随访期于2012年7月结束。
干预措施：所有患者除标准治疗外，每日接受150mg（耐受情况下增加至300mg）阿利吉仑或安慰剂。出院后研究药物继续使用，中位数持续时间为11.3个月。
主要结局指标：6个月和12个月时的心血管死亡或心力衰竭再住院情况。
结果：共有1639例患者被随机分组，1615例患者纳入最终疗效分析队列（808例使用阿利吉仑，807例使用安慰剂）。平均年龄为65岁；平均LVEF为28%；41%的患者患有糖尿病，平均估计肾小球滤过率为67 mL/min/1.73 m²。入院和随机分组时，NT - proBNP中位数水平分别为4239 pg/mL和2718 pg/mL。随机分组时，患者正在使用利尿剂（95.9%）、β - 受体阻滞剂（82.5%）、血管紧张素转换酶抑制剂或血管紧张素II受体阻滞剂（84.2%）以及盐皮质激素受体拮抗剂（57.0%）。总计，24.9%接受阿利吉仑治疗的患者（77例心血管死亡，153例心力衰竭再住院）和26.5%接受安慰剂治疗的患者（85例心血管死亡，166例心力衰竭再住院）在6个月时出现主要终点事件（风险比[HR]，0.92；95%置信区间，0.76 - 1.12；P = 0.41）。在12个月时，阿利吉仑组事件发生率为35.0%（126例心血管死亡，212例心力衰竭再住院），安慰剂组为37.3%（137例心血管死亡，224例心力衰竭再住院；HR，0.93；95%置信区间，0.79 - 1.09；P = 0.36）。与安慰剂组相比，阿利吉仑组高钾血症、低血压以及肾功能损害/肾衰竭的发生率更高。
结论和相关性：在因心力衰竭住院且LVEF降低的患者中，在标准治疗基础上加用阿利吉仑并未降低出院后6个月或12个月的心血管死亡或心力衰竭再住院率。
试验注册：clinicaltrials.gov标识符：NCT00894387
《美国医学会杂志》2013年；309(11):1125 - 1135
2013年3月11日在线发表。doi:10.1001/jama.2013.1954
www.jama.com
Importance Hospitalizations for heart failure (HHF) represent a major health burden, with high rates of early postdischarge rehospitalization and mortality.Objective To investigate whether aliskiren, a direct renin inhibitor, when added to standard therapy, would reduce the rate of cardiovascular (CV) death or HF rehospitalization among HHF patients.Design, Setting, and Participants International, double-blind, placebo-controlled study that randomized hemodynamically stable HHF patients a median 5 days after admission. Eligible patients were 18 years or older with left ventricular ejection fraction (LVEF) 40% or less, elevated natriuretic peptides (brain natriuretic peptide [BNP] >= 400 pg/mL or N-terminal pro-BNP [NT-proBNP] >= 1600 pg/mL), and signs and symptoms of fluid overload. Patients were recruited from 316 sites across North and South America, Europe, and Asia between May 2009 and December 2011. The follow-up period ended in July 2012.Intervention All patients received 150mg(increased to 300 mg as tolerated) of aliskiren or placebo daily, in addition to standard therapy. The study drug was continued after discharge for a median 11.3 months.Main Outcome Measures Cardiovascular death or HF rehospitalization at 6 months and 12 months.Results In total, 1639 patients were randomized, with 1615 patients included in the final efficacy analysis cohort (808 aliskiren, 807 placebo). Mean age was 65 years; mean LVEF, 28%; 41% of patients had diabetes mellitus, mean estimated glomerular filtration rate, 67 mL/min/1.73 m(2). At admission and randomization, median NT-proBNP levels were 4239 pg/mL and 2718 pg/mL, respectively. At randomization, patients were receiving diuretics (95.9%), beta-blockers (82.5%), angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (84.2%), and mineralocorticoid receptor antagonists (57.0%). In total, 24.9% of patients receiving aliskiren (77 CV deaths, 153 HF rehospitalizations) and 26.5% of patients receiving placebo (85 CV deaths, 166 HF rehospitalizations) experienced the primary end point at 6 months (hazard ratio [HR], 0.92; 95% CI, 0.76-1.12; P=.41). At 12 months, the event rates were 35.0% for the aliskiren group (126 CV deaths, 212 HF rehospitalizations) and 37.3% for the placebo group (137 CV deaths, 224 HF rehospitalizations; HR, 0.93; 95% CI, 0.79-1.09; P=.36). The rates of hyperkalemia, hypotension, and renal impairment/renal failure were higher in the aliskiren group compared with placebo.Conclusion and Relevance Among patients hospitalized for HF with reduced LVEF, initiation of aliskiren in addition to standard therapy did not reduce CV death or HF rehospitalization at 6 months or 12 months after discharge.Trial Registration clinicaltrials.gov Identifier: NCT00894387 JAMA. 2013;309(11):1125-1135 Published online March 11, 2013. doi:10.1001/jama.2013.1954 www.jama.com