瑞士巴塞尔大学Christian Mueller研究团队近期取得进展。他们分析了综合血管舒张与常规护理对急性心力衰竭患者死亡和再住院治疗的影响。相关论文于2019年12月17日发表在《美国医学会杂志》上。

在急性心力衰竭（AHF）患者中，短期输注单血管扩张剂（通过为固定剂量）并未改善预后。

2007年12月至2019年2月，研究组在瑞士、保加利亚、德国、巴西和西班牙的10家三级和二级医院进行了一项随机、开放标签、盲终点试验，招募了788名呼吸困难、血浆钠尿肽浓度升高、收缩压至少为100mmHg的AHF住院患者。

将其按1：1随机分组，其中386例在整个住院期间采取早期强化和持续血管舒张的治疗方案，402例患者则进行常规治疗。其中早期强化和持续血管舒张是一种综合实用的最大持续血管扩张的方法，结合个体舌下含服和经皮硝酸盐、低剂量口服肼屈嗪48小时，以及快速输注血管紧张素转换酶抑制剂、血管紧张素受体阻断剂或缬沙坦等。

共有779例患者完成试验并接受180天随访。干预组中有30.6%的患者发生全因死亡或因AHF再次住院，其中死亡率为14.4%，常规治疗组有27.8%，死亡率为15.3%。干预组和常规治疗组中最常见的临床不良事件为低钾血症（23%与25%）、肾功能恶化（21%与20%）、头痛（26%与10%）、头晕（15%与10%）和低血压（8%和2%）。

总之，与常规治疗相比，AHF患者早期强化和持续血管舒张治疗方案并不能显著改善半年内的全因死亡率和AHF再住院的综合风险。

附：英文原文

Title: 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

Author: Nikola Kozhuharov, Assen Goudev, Dayana Flores, Micha T. Maeder, Joan Walter, Samyut Shrestha, Danielle Menosi Gualandro, Mucio Tavares de Oliveira Junior, Zaid Sabti, Beat Müller, Markus Noveanu, Thenral Socrates, Ronny Ziller, Antoni Bayés-Genís, Alessandro Sionis, Patrick Simon, Eleni Michou, Samuel Gujer, Tommaso Gori, Philip Wenzel, Otmar Pfister, David Conen, Ioannis Kapos, Richard Kobza, Hans Rickli, Tobias Breidthardt, Thomas Münzel, Paul Erne, Christian Mueller

Issue&Volume: 2019/12/17

Abstract:

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

Objective  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.

Design, Setting, and Participants  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.

Interventions  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.

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

Results  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%).

Conclusions and Relevance  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.

DOI: 10.1001/jama.2019.18598

Source: https://jamanetwork.com/journals/jama/article-abstract/2757580