Effect of Ularitide on Cardiovascular Mortality in Acute Heart Failure
Effect of Ularitide on Cardiovascular Mortality in Acute Heart Failure
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DOI：
10.1056/nejmoa1601895
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发表时间：
2017-05-18
影响因子：
158.5
通讯作者：
Holzmeister, J.
中科院分区：
文献类型：
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作者：
Packer, M.;O'Connor, C.;Holzmeister, J.
背景对于急性心力衰竭患者，已提出早期静脉注射血管扩张剂干预作为治疗目标，以减少心壁应力和潜在的心肌损伤，从而有利地影响患者的长期预后。 方法在这项双盲试验中，我们随机分配 2157 名急性心力衰竭患者接受连续静脉输注乌拉立肽，剂量为 15 ng/kg 体重/分钟或匹配的安慰剂 48 小时，此外，治疗。初始临床评估后平均 6 小时开始治疗。共同主要结局是中位随访 15 个月期间因心血管原因死亡，以及评估初始 48 小时临床病程的分层复合终点。 结果 乌拉立肽组 236 名患者和安慰剂组 225 名患者发生心血管原因死亡（21.7% vs. 21.0%；风险比，1.03；96% 置信区间，0.85 至 1.25； P=0.75）。在意向治疗分析中，分层综合结果没有显着的组间差异。乌拉立肽组的收缩压和 N 末端脑钠肽前体水平比安慰剂组有更大的降低。然而，在55%的配对数据患者中，输注期间心肌肌钙蛋白T水平的变化在两组之间没有差异。结论在急性心力衰竭患者中，乌拉立肽发挥了良好的生理作用（不影响心肌肌钙蛋白水平），但短期治疗不会影响临床复合终点或降低长期心血管死亡率。 （由 Cardiorentis 资助；TRUE-AHF ClinicalTrials.gov 编号，NCT01661634。）
BACKGROUNDIn patients with acute heart failure, early intervention with an intravenous vasodilator has been proposed as a therapeutic goal to reduce cardiac-wall stress and, potentially, myocardial injury, thereby favorably affecting patients' long-term prognosis.METHODSIn this double-blind trial, we randomly assigned 2157 patients with acute heart failure to receive a continuous intravenous infusion of either ularitide at a dose of 15 ng per kilogram of body weight per minute or matching placebo for 48 hours, in addition to accepted therapy. Treatment was initiated a median of 6 hours after the initial clinical evaluation. The coprimary outcomes were death from cardiovascular causes during a median follow-up of 15 months and a hierarchical composite end point that evaluated the initial 48-hour clinical course.RESULTSDeath from cardiovascular causes occurred in 236 patients in the ularitide group and 225 patients in the placebo group (21.7% vs. 21.0%; hazard ratio, 1.03; 96% confidence interval, 0.85 to 1.25; P=0.75). In the intention-to-treat analysis, there was no significant between-group difference with respect to the hierarchical composite outcome. The ularitide group had greater reductions in systolic blood pressure and in levels of N-terminal pro-brain natriuretic peptide than the placebo group. However, changes in cardiac troponin T levels during the infusion did not differ between the two groups in the 55% of patients with paired data.CONCLUSIONSIn patients with acute heart failure, ularitide exerted favorable physiological effects (without affecting cardiac troponin levels), but short-term treatment did not affect a clinical composite end point or reduce long-term cardiovascular mortality. (Funded by Cardiorentis; TRUE-AHF ClinicalTrials.gov number, NCT01661634.)