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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, 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

Kurzfassung

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.
   
Zitation Kozhuharov N, Goudev A, Flores D, Maeder M T, Walter J, Shrestha S, Gualandro D M, De Oliveira Junior M T, Sabti Z, Müller B, Noveanu M, Socrates T, Ziller R, Bayés-Genís A, Sionis A, Simon P, Michou E, Gujer S, Gori T, Wenzel P, Pfister O, Conen D, Kapos I, Kobza R, Rickli H, Breidthardt T, Münzel T, Erne P, Mueller C, GALACTIC Investigators . 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. JAMA 2019; 322:2292-2302.
   
Typ Wissenschaftlicher Artikel/Review (Englisch)
Veröffentlichungsdatum 2019
Titel der Zeitschrift JAMA (322/23)
ISSN electronic 1538-3598
Seiten 2292-2302
PubMed 31846016
DOI 10.1001/jama.2019.18598