Impact of in-hospital intensification of heart failure medical treatment on clinical outcomes in dialysis-dependent patients with worsening heart failure

Abstract

Patients undergoing maintenance dialysis represent a high-risk population for cardiovascular events. Major randomised trials evaluating guideline-directed medical therapy (GDMT) components for heart failure (HF), such as renin-angiotensin system inhibitors (RASis), angiotensin receptor neprilysin inhibitor (ARNI), β-blockers (BBs), mineralocorticoid receptor antagonists (MRAs), and sodium-glucose cotransporter 2 inhibitors (SGLT2is), have largely excluded dialysis patients, resulting in uncertainty regarding the applicability and prognostic relevance of GDMT in this population. We aimed to evaluate the real-world GDMT utilisation in dialysis-dependent patients hospitalised for HF and to determine the prognostic significance of in-hospital GDMT intensification. We analysed the data of the Quality of Heart Failure Care and Outcomes Registry Retrospective Cohort (QHEART-R) study, a multicentre registry of patients hospitalised for worsening HF from October 2020 through December 2024 at 6 institutions in Japan. In-hospital GDMT intensification was quantitatively assessed by the change in the Simple GDMT score from admission to discharge (∆S-GDMT). The primary outcome was 2-year composite of all-cause death or HF hospitalisation. Among the QHEART-R cohort,129 patients were dialysis-dependent, including 63 HFrEF and 29 HFmrEF. The changes in medication during hospitalisation were documented (Figure 1). At discharge, prescription rates were 45.6% for RASis, 26.5% for ARNI, 72.1% for BBs, 23.5% for MRAs, and 8.8% for SGLT2is. Patients with HFrEF and HFmrEF were categorised as in-hospital HF medical treatment intensification (Δ≥1) or non-intensification (Δ≤0) groups; 51 and 41, respectively. Baseline characteristics were comparable between two groups. During the 2-year follow-up, 18 composite events occurred. In-hospital HF medical treatment intensification was associated with a markedly lower risk of the composite event (p=0.012 for log-rank test), and restricted mean survival time analysis demonstrated clinically meaningful benefits: +104.6 days at 2 years and +295.1 days over the entire follow-up (Figure 2). The crude hazard ratio (HR) of in-hospital intensification was 0.30 (95% CI 0.11–0.81); this remained significant after multivariate analysis incorporating age, sex, and LVEF (0.34, 95% CI 0.13–0.91). Drug-specific analyses identified RASis intensification as the strongest contributor to the improved prognosis. In dialysis-dependent patients hospitalised for worsening HF, in-hospital intensification of medical treatment was associated with significantly better 2-year outcomes compared to the non-intensification patients. Targeted optimisation of heart failure medical treatment may provide meaningful clinical improvement even in the dialysis-dependent patients, although the conventional up-titration of GDMT is often limited by risks of adverse effects in this population.