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.

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.

Trial Registration:

ClinicalTrials.gov Identifier: NCT00512759.

• Authors: 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, GALACTIC Investigators, Christian Mueller, Paul Erne, Beat Müller, Hans Rickli, Micha Maeder, Mucio Tavares de Oliveira Jr, Thomas Münzel, Antoni Bayés-Genís, Alessandro Sionis, Assen Goudev, Bojidar Dimov, Sabine Hartwiger, Nisha Arenja, Bettina Glatz, Natascha Herr, Rahel Isenrich, Tamina Mosimann, Raphael Twerenbold, Jasper Boeddinghaus, Thomas Nestelberger, Christian Puelacher, Michael Freese, Janine Vögele, Kathrin Meissner, Jasmin Martin, Ivo Strebel, Desiree Wussler, Carmela Schumacher, Stefan Osswald, Fabian Vogt, Jonas Hilti, Sara Barata, Deborah Schneider, Jonas Schwarz, Brigitte Fitze, Sabine Hartwiger, Nisha Arenja, Bettina Glatz, Natascha Herr, Rahel Isenrich, Tamina Mosimann, Raphael Twerenbold, Jasper Boeddinghaus, Thomas Nestelberger, Christian Puelacher, Michael Freese, Janine Vögele, Kathrin Meissner, Jasmin Martin, Ivo Strebel, Desiree Wussler, Carmela Schumacher, Stefan Osswald, Fabian Vogt, Jonas Hilti, Sara Barata, Deborah Schneider, Jonas Schwarz, Brigitte Fitze, Nisha Arenja, Katharina Rentsch, Aline Bossa, Sergio Jallad, Alexandre Soeiro, Dimitar Georgiev, Thomas Jansen, Gabriele Gebel, Matthias Bossard, Michael Christ
• Journal: JAMA (JAMA) Vol. 322 Issue 23 Pg. 2292-2302 (12 17 2019) ISSN: 1538-3598 [Electronic] United States
• PMID: 31846016 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Vasodilator Agents

Topics

• Acute Disease
• Aged
• Aged, 80 and over
• Cause of Death
• Comorbidity
• Drug Administration Schedule
• Female
• Heart Failure (drug therapy, mortality)
• Hospitalization
• Humans
• Male
• Patient Readmission (statistics & numerical data)
• Vasodilator Agents (administration & dosage, adverse effects)