Comprehensive vasodilatation in women with acute heart failure: Novel insights from the GALACTIC randomized controlled trial

Aims Sex‐specific differences in acute heart failure (AHF) are both relevant and underappreciated. Therefore, it is crucial to evaluate the risk/benefit ratio and the implementation of novel AHF therapies in women and men separately. Methods and results We performed a pre‐defined sex‐specific analysis in AHF patients randomized to a strategy of early intensive and sustained vasodilatation versus usual care in an international, multicentre, open‐label, blinded endpoint trial. Inclusion criteria were AHF with increased plasma concentrations of natriuretic peptides, systolic blood pressure ≥100 mmHg, and plan for treatment in a general ward. Among 781 eligible patients, 288 (37%) were women. Women were older (median 83 vs. 76 years), had a lower body weight (median 64.5 vs. 77.6 kg) and lower estimated glomerular filtration rate (median 48 vs. 54 ml/min/1.73 m2). The primary endpoint, a composite of all‐cause mortality or rehospitalization for AHF at 180 days, showed a significant interaction of treatment strategy and sex (p for interaction = 0.03; hazard ratio adjusted for female sex 1.62, 95% confidence interval 1.05–2.50; p = 0.03). The combined endpoint occurred in 53 women (38%) in the intervention group and in 35 (24%) in the usual care group. The implementation of rapid up‐titration of renin–angiotensin–aldosterone system (RAAS) inhibitors was less successful in women versus men in the overall cohort and in patients with heart failure with reduced ejection fraction (median discharge % target dose in patients randomized to intervention: 50% in women vs. 75% in men). Conclusion Rapid up‐titration of RAAS inhibitors was less successfully implemented in women possibly explaining their higher rate of all‐cause mortality and rehospitalization for AHF. Clinical Trial Registration: ClinicalTrials.gov, unique identifier NCT00512759. In patients randomized to a strategy of early intensive and sustained vasodilatation or usual care, the combined primary endpoint showed a significant interaction of treatment strategy and sex. Women randomized to intervention significantly more often experienced the combined endpoint when comapred to standard of care. AHF, acute heart failure. [Correction added on 15 January 2024, after first online publication: abbreviation has been added in this version.]