Comprehensive vasodilation strategy fails to improve outcomes in acute HFNews - Sep. 2, 2019
Introduction and methods
Acute heart failure (AHF) affects about 2,000,000 patients per year. Symptomatic improvement can be obtained with loop diuretics, but morbidity and mortality remain high. The optimal treatment for AHF is largely unknown. It is known that IV nitrates can improve outcome in severe pulmonary edema, which represents about 5% of all AHF. That raises the question whether aggressive vasodilation also improves outcomes in less severe AHF, which means 95% of AHF cases.
The GALACTIC study tested the hypothesis that a comprehensive strategy is better than a single drug in reducing pulmonary capillary wedge pressure, increasing organ perfusion, and increasing the use of ACE-I/ARB/ARNI.
GALACTIC represents the largest investigator-initiated randomized clinical trial in AHF. The research project was funded by public sources only. It evaluated not a single drug, but a comprehensive strategy of early intensive and sustained vasodilation, using individualized doses of well-characterized, widely available and mostly inexpensive drugs. This way, when successful, the protocol could be immediately implemented in many countries. Therapy was uptitrated on consecutive days.
Adult patients presenting with AHF to the emergency department with NYHA class III/IV, elevated BNP/NT-proBNP and systolic BP ≥100 mmHg, were randomized to standard of care (n=399) or the early intensive and sustained vasodilation (n=382). All other therapies and follow-up care were given according to ESC guidelines and at the discretion of the treating physician in both groups.
- The event curves for the primary endpoint (death or AHF) were mostly on top of each other, resembling the adjusted HR of 1.07 (95%CI: 0.83 – 1.39, P=0.592).
In a broad AHF population, early intensive and sustained vasodilation with nitrates, hydralazine, ACE inhibitors, ARB or sacubitril/valsartan using individualized doses was well tolerated, but did not improve 180-day all-cause mortality and AHF hospitalizations.
This study has implications for research, because the findings suggest that pulmonary congestion, although the hallmark of AHF, may not be the ideal treatment target. Moreover, the failure to improve outcomes with this strategy not only has impact on clinical practice, as AHF will continue to have high morbidity and mortality rates, but also affects cardiology in general. These data emphasize that every attempt must be made to prevent HF, detect and treat it early, to avoid progression to AHF.
A question during the press conference was whether patients felt better. Mueller said that the study looked into shortness of breath on a semi-quantitative scale, but no significant difference was found between groups, nor at sitting position (60% reclined) nor when lying down. Concerning adverse effects, they saw effects that were expected based on the medications used, such as headache. Systolic arterial hypertension was more frequent in the intensively treated group (8% vs. 2%), but worsening renal function was similar in both groups.
When asked what he aims to do next, Mueller answered that he thinks that the effect of loop diuretic therapy is not appreciated enough: he is sure it can do good things, but a better strategy is needed. He thinks that regular uptitration and regular clinic visits are needed.
He also emphasized that the biggest impact with preventive measures can be made in primary care. It is therefore important, for instance, to have measurements of natriuretic peptides available in primary care to detect HF in an early stage.
- Our reporting is based on the information provided at the ESC congress -