Risk-Stratified Transitional Care and Cardiovascular Hospitalizations by Sex: A Secondary Analysis of a Randomized Clinical Trial.

Abstract

Female patients with heart failure (HF) are older and more often present with preserved left ventricular ejection fraction (LVEF), whereas male patients present with more ischemic disease. Despite these differences, an emergency department-based acute HF strategy may be equally applicable to both sexes. To determine whether the strategy for acute HF management in the Comparison of Outcomes and Access to Care for Heart Failure (COACH) trial differed by sex. This prespecified secondary analysis of the multicenter COACH stepped-wedge, cluster-randomized clinical trial included 10 acute care hospitals in Ontario, Canada. Data were collected from January 15, 2017, to January 15, 2019. Participants included patients presenting to a study emergency department with acute HF. Cox proportional hazards regression with interactions was used to evaluate whether intervention effects differed for females and males and to estimate sex-specific association with treatment. Data were analyzed from July 2024 to May 2025. Risk stratification for disposition decisions from the emergency department and risk-guided postdischarge transitional care, examining sex interactions. Composite of death or cardiovascular hospitalizations at 30 days (primary outcome) and during extended follow-up to 20 months (co-primary outcome). A total of 5452 patients were included in the analysis (median age, 78.0 [IQR, 68.0-85.0] years). The 2461 females were older (median age, 80.0 [IQR, 71.0-87.0] years) than the 2991 males (median age, 76.0 [IQR, 66.0-84.0] years). Females had more preserved LVEF (≥50%) compared with males (1107 [45.0%] vs 885 [29.6%]; standardized mean difference, 0.32). Males had more prior myocardial infarction compared with females (565 [18.9%] vs 338 [13.7%]; standardized mean difference, 0.14). There was no interaction by sex at 30 days (hazard ratios [HRs] for primary outcome, 0.88 [95% CI, 0.68-1.14] for females and 0.88 [95% CI, 0.71-1.08] for males; P = .98 for interaction) or 20 months (HRs for co-primary outcome, 0.99 [95% CI, 0.90-1.09] in females and 0.92 [95% CI, 0.85-1.00] in males; P = .38 for interaction). There was a significant interaction by sex for 20-month HF readmissions (P = .01 for interaction), with adjusted HRs of 0.92 (95% CI, 0.72-1.19) in females and 0.71 (95% CI, 0.58-0.87) in males. There were no sex interactions for other outcomes at either time point. In this secondary analysis of a stepped-wedge, cluster-randomized clinical trial, risk stratification for emergency department-based decision-making for disposition decisions and rapid postdischarge transitional care was similarly beneficial in males and females, with comparable outcomes after accounting for multiplicity. ClinicalTrials.gov Identifier: NCT02674438.