Original Investigation December 17, 2019

Effect of a Strategy of Comprehensive Vasodilation vs Usual Care on Mortality and Heart Failure Rehospitalization Among Patients With Acute Heart Failure: The GALACTIC Randomized Clinical Trial

Nikola Kozhuharov, Assen Goudev, Dayana Flores, et al

JAMA. 2019;322(23):2292-2302. doi:10.1001/jama.2019.18598

Importance 背景

Short-term infusions of single vasodilators, usually given in a fixed dose, have not improved outcomes in patients with acute heart failure (AHF).

短期输注一种血管扩张剂（通常为固定剂量）不能改善急性心衰(AHF)患者的预后。

Objective 目的 

To evaluate the effect of a strategy that emphasized early intensive and sustained vasodilation using individualized up-titrated doses of established vasodilators in patients with AHF.

评价通过个体化上调血管扩张剂的剂量进行早期强化且持续血管扩张策略对AHF患者的疗效。

Design, Setting, and Participants 设计，场景及研究人群

Randomized, open-label blinded-end-point trial enrolling 788 patients hospitalized for AHF with dyspnea, increased plasma concentrations of natriuretic peptides, systolic blood pressure of at least 100 mm Hg, and plan for treatment in a general ward in 10 tertiary and secondary hospitals in Switzerland, Bulgaria, Germany, Brazil, and Spain. Enrollment began in December 2007 and follow-up was completed in February 2019.

这项随机、开放标签、终点设盲临床试验在瑞士、保加利亚、德国、巴西和西班牙的10个三级和二级医院的普通病房进行，入选788名伴随呼吸困难、血浆利钠肽水平升高、收缩压至少100 mmHg且需要接受治疗的AHF住院患者。

Interventions 干预措施

Patients were randomized 1:1 to a strategy of early intensive and sustained vasodilation throughout the hospitalization (n = 386) or usual care (n = 402). Early intensive and sustained vasodilation was a comprehensive pragmatic approach of maximal and sustained vasodilation combining individualized doses of sublingual and transdermal nitrates, low-dose oral hydralazine for 48 hours, and rapid up-titration of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or sacubitril-valsartan.

患者按照1:1的比例随机分至早期强化及持续血管扩张策略 (n = 386) 或常规治疗 (n = 402)。早期强化及持续血管扩张指维持最大化且持续血管扩张的综合措施，联合使用个体化舌下和经皮硝酸酯，口服小剂量肼苯哒嗪48小时，快速上调ACEI、ACB或沙库巴曲缬沙坦剂量。

Main Outcomes and Measures 主要预后终点

The primary end point was a composite of all-cause mortality or rehospitalization for AHF at 180 days.

主要预后终点为复合指标，包括180天内全因病死率或因AHF再入院率。

Results 结果

Among 788 patients randomized, 781 (99.1%; median age, 78 years; 36.9% women) completed the trial and were eligible for primary end point analysis. Follow-up at 180 days was completed for 779 patients (99.7%). The primary end point, a composite of all-cause mortality or rehospitalization for AHF at 180 days, occurred in 117 patients (30.6%) in the intervention group (including 55 deaths [14.4%]) and in 111 patients (27.8%) in the usual care group (including 61 deaths [15.3%]) (absolute difference for the primary end point, 2.8% [95% CI, −3.7% to 9.3%]; adjusted hazard ratio, 1.07 [95% CI, 0.83-1.39]; P = .59). The most common clinically significant adverse events with early intensive and sustained vasodilation vs usual care were hypokalemia (23% vs 25%), worsening renal function (21% vs 20%), headache (26% vs 10%), dizziness (15% vs 10%), and hypotension (8% vs 2%).

共有788名患者接受随机分组，781名 (99.1%; 中位年龄, 78 岁; 36.9% 女性) 完成试验，纳入主要终点分析。779名 (99.7%) 患者完成180天随访。干预组117名患者(30.6%) (包括 55 例死亡 [14.4%]) 及常规治疗组 111 名 (27.8%) 患者 (包括 61 例死亡 [15.3%]) 发生主要预后终点事件，即180天全因病死率或因AHF再入院率 (主要预后终点绝对差异, 2.8% [95% CI, −3.7% to 9.3%]; 校正后风险比, 1.07 [95% CI, 0.83-1.39]; P = .59)。早期强化持续血管扩张与常规治疗最常见的有临床意义的不良事件包括低钾血症 (23% vs 25%)，肾功能恶化 (21% vs 20%)，头疼 (26% vs 10%)，头晕 (15% vs 10%) 和低血压 (8% vs 2%)。

Conclusions and Relevance 结论与意义

Among patients with AHF, a strategy of early intensive and sustained vasodilation, compared with usual care, did not significantly improve a composite outcome of all-cause mortality and AHF rehospitalization at 180 days.

对于AHF患者，与常规治疗相比，早期强化持续血管扩张策略不能显著改善复合预后指标（包括180天全因病死率及AHF再次住院）。

Trial Registration 试验注册

ClinicalTrials.gov Identifier: NCT00512759