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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

Author Affiliations
  • 1Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, University of Basel, Basel, Switzerland
  • 2GREAT Research Network, Rome, Italy
  • 3Queen Ioanna University Hospital Sofia, Department of Cardiology, Medical University of Sofia, Sofia, Bulgaria
  • 4Department of Cardiology, Kantonsspital St Gallen, St Gallen, Switzerland
  • 5Department of Internal Medicine, University Hospital Basel, University of Basel, Basel, Switzerland
  • 6Heart Institute (INCOR), University of Sao Paulo Medical School, Sao Paulo, Brazil
  • 7Department of General Internal and Emergency Medicine, Medical University Clinic of the University of Basel, Kantonsspital Aarau, Aarau, Switzerland
  • 8Medical Outpatient Department, University Hospital Basel, University of Basel, Basel, Switzerland
  • 9Heart Institute, Hospital Universitari Germans Trias i Pujol, CIBERCV, Department of Medicine, Autonomous University of Barcelona, Barcelona, Spain
  • 10Intensive Cardiac Care Unit, Cardiology Department, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute IIB-Sant Pau, Autonomous University of Barcelona, Barcelona, Spain
  • 11Clinical Trial Unit, University Hospital Basel, Basel, Switzerland
  • 12Department of Cardiology, Luzerner Kantonsspital, Luzern, Switzerland
  • 13Department of Internal Medicine, Kantonsspital Obwalden, Sarnen, Switzerland
  • 14University Medical Center, Johannes Gutenberg University Mainz, Mainz, Germany
  • 15Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada
  • 16Department of Cardiology, University Hospital Zurich, Zurich, Switzerland
JAMA. 2019;322(23):2292-2302. doi:10.1001/jama.2019.18598
Key Points

Question  Does a comprehensive approach of early intensive and sustained vasodilation, using a combination of nitrates, hydralazine, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and sacubitril-valsartan, improve outcomes in patients with acute heart failure?

Findings  In this randomized clinical trial that included 788 patients hospitalized for acute heart failure, a strategy that emphasized early intensive and sustained vasodilation, compared with usual care, resulted in no significant difference in the primary end point of 180-day all-cause mortality and acute heart failure rehospitalizations (30.6% vs 27.8%, respectively).

Meaning  Among patients with acute heart failure, a strategy of comprehensive vasodilation, compared with usual care, did not significantly improve a composite outcome of all-cause mortality and acute heart failure rehospitalizations at 180 days.

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

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