GALACTIC may suggest moving on to other targets
PARIS -- Early intensive and sustained vasodilation failed to improve outcomes in acute heart failure, a randomized trial found.
Among nearly 800 patients in GALACTIC, the rate of new heart failure hospitalization or death at 180 days was 30.6% with the aggressive, individualized approach versus 27.8% with standard treatment (adjusted HR 1.07, P=0.592), reported Christian Mueller, MD, of the University Hospital in Basel, Switzerland.
"Even when applied within a comprehensive strategy using individualized doses, intensive vasodilation was unable to improve outcomes," Mueller said here at the European Society of Cardiology (ESC) congress. "Therefore, acute heart failure will continue to have unacceptably high mortality and morbidity."
The intervention involved personalized, high doses of inexpensive and universally available vasodilators, including transdermal and sublingual nitrates starting on day 1, oral hydralazine for 48 hours to prevent tolerance to nitrates, and then rapid uptitration of angiotensin II receptor blockers (ARBs) or ACE inhibitors.
All other therapies (including aldosterone antagonists, beta-blockers, cardiac devices, and loop diuretic dose), duration of treatment, and follow-up care were at the discretion of the physician and according to ESC guidelines in both cohorts.
Although pulmonary congestion is a hallmark of acute heart failure, it may not be the optimal therapy target, Mueller emphasized.
"Although it's neutral, it is an important step forward in acute heart failure," said session discussant Alexandre Mebazaa, MD, PhD, of Universite de Paris in France. There were limitations to the trial, he noted -- it was open label and patients from the two arms were treated at the same centers.
No prespecified subgroups appeared to benefit from the intervention, and women appeared to fare worse.
From baseline to day 6, both groups saw similar improvements in dyspnea, a secondary endpoint. Adverse events were significantly more frequent in the intervention group (82% vs 75% with standard care), with headache (26% vs 10%) and systolic arterial hypotension (8% vs 2%) both more common with the intervention.
Mebazaa called the data on women "intriguing" and questioned whether the higher rate of the primary outcome was driven by new heart failure hospitalizations or death. Women in the investigational arm experienced a higher rate of new heart failure hospitalizations or death versus those on standard care (38% vs 23%; adjusted HR 1.67, 95% CI 1.08-2.59).
"I have to be honest, I would not over-interpret this because I am not aware that this is a finding that has also been seen in other heart failure studies," said Stephan Gielen, MD, of Klinikum Lippe in Detmold, Germany, who was not involved in the study.
Gielen noted that the causes of heart failure often diverge between men and women.
"You have a higher prevalence of hypertensive decompensation among women, and the prevalence of ischemic heart disease as a cause of decompensation is greater in men, so it may also be a little bit of a different underlying pathophysiology," he told MedPage Today.
Rehospitalization after a first decompensated heart failure event is very high, Gielen emphasized, with a substantial proportion of patients returning to the hospital within 3 to 6 months, highlighting the need for optimal care between general practitioners and treating hospitals.
Christian Mueller, MD, presenting the data at an ESC press briefing
For GALACTIC, Mueller's group randomized 399 patients who presented to the emergency department with acute heart failure to standard care based on ESC guidelines, and 382 patients to the early individualized intensive protocol. Median patient age was 78, and 37% of the participants were women.
Inclusion criteria included elevated B-type natriuretic peptide (BNP) or N-terminal-pro hormone BNP (NT-proBNP) and acute dyspnea (New York Heart Association III or IV). Exclusion criteria were known severe mitral or aortic stenosis, cardiopulmonary resuscitation, severe kidney dysfunction, adult congenital heart disease, systolic blood pressure <100 mm Hg, isolated right ventricular failure as a result of pulmonary hypertension, need for urgent coronary intervention or ICU admission, and hypertrophic obstructive cardiomyopathy.
Limitations included slow enrollment, and that the open-label design may have led to bias in the unblinded evaluation of dyspnea, said Mueller.
The study was funded by the University Hospital Basel, the Stanley Thomas Johnson Foundation, the Foundation for Cardiovascular Research Basel, and the Swiss National Science Foundation.
Mueller disclosed relationships with Novartis, Roche Diagnostic, Abbott, Boehringer Ingelheim, Singulex, BRAHMS, and Cardiorentis.
Mebazaa disclosed relationships with Roche, Adrenomed, SphingoTec, 4TEEN4, Novartis, AstraZeneca, S-Form Pharma, and Servier.
Gielen reported no disclosures.
European Society of Cardiology
Source Reference: Mueller CE, et al "Effect of comprehensive vasodilation in acute heart failure: The GALACTIC randomized clinical trial" ESC 2019; Abstract 3178.
Read the original article on Medpage Today: Aggressive Vasodilation Flops in Acute Heart Failure