(A-113) Dosage adjustment pattern of renin-angiotensin system inhibitors in heart failure patients with severe renal dysfunction: A Nationwide Cohort

Background: Renin-angiotensin system inhibitors (RASi) are essential for heart failure (HF) treatment, but their use in patients with severe renal dysfunction remains uncertain. Although clinical guidelines yet provide specific suggestions, advanced chronic kidney disease (CKD; eGFR < 30 mL/min/1.73 m²) has been a contraindication in HF trials.

Objectives: To evaluate the comparative effectiveness and safety of RASi prescription adjustment strategies on clinical outcomes in HF patients with severe renal dysfunction.

Methods: We analyzed 2,038 adult HF patients with stable RASi use before developing advanced CKD (eGFR < 30 mL/min/1.73m²) from 2017 to 2022 using Taiwan’s National Health Insurance Research Database. Patients with prior kidney transplantation, dialysis, or death within 30 days were excluded. Based on baseline RASi use, patients were classified into a maintenance group (≥0.75 of baseline DDD) or a reduction group ( < 0.75). Primary outcomes included all-cause mortality, HF hospitalization, major adverse cardiovascular events (MACE) and its components (cardiovascular death [CV death], acute myocardial infarction [AMI], non-fatal stroke), with end-stage renal disease (ESRD) as the safety outcome. Cox proportional hazards models with inverse probability treatment weighting (IPTW) were used to compare the risk of all-cause mortality, cardiovascular outcomes, and ESRD between groups. The results were reported as adjusted hazard ratios (aHR) with 95% confidence intervals (CIs).

Results: IPTW achieved a balanced distribution of baseline characteristics between the maintenance (n=1,316) and reduction (n=722) groups. RASi dose reduction was associated with increased risks of all-cause mortality (aHR: 1.18 [95% CI: 1.04–1.33]), HF hospitalization (aHR: 1.17 [95% CI: 1.04–1.32]), and CV death (aHR: 1.47 [95% CI: 1.14–1.90]). No significant differences were observed for MACE (aHR: 1.05 [95% CI: 0.91–1.21]), stroke (aHR: 0.97 [95% CI: 0.79–1.18]), AMI (aHR: 1.06 [95% CI: 0.83–1.35]), or ESRD progression (aHR: 1.08 [95% CI: 0.87–1.35]).

Conclusions: In HF patients receiving chronic RASi therapy who develop advanced CKD, RASi dose reduction was associated with an increased risk of all-cause mortality, cardiovascular death, and HF hospitalization, without providing a protective effect against ESRD progression. Clinicians must carefully balance cardiovascular and renal risks when managing these patients.