1. 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
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Kozhuharov, N, Goudev, A, Flores, D, Maeder, MT, Walter, J, Shrestha, S, Gualandro, DM, de Oliveira, MT, Sabti, Z, Muller, B, Noveanu, M, Socrates, T, Ziller, R, Bayes-Genis, 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, Munzel, T, Erne, P, Mueller, C, Dimov, B, Herr, N, Isenrich, R, Mosimann, T, Twerenbold, R, Boeddinghaus, J, Nestelberger, T, Puelacher, C, Freese, M, Vogele, J, Meissner, K, Martin, J, Strebel, I, Wussler, D, Schumacher, C, Osswald, S, Vogt, F, Hilti, J, Schwarz, J, Fitze, B, Hartwiger, S, Arenja, N, Glatz, B, Rentsch, K, Bossa, A, Jallad, S, Soeiro, A, Jansen, T, Gebel, G, Bossard, M, and Christ, M
- 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 100mmHg, 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 pointwas 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.
- Published
- 2019