Impact of renin-angiotensin system inhibitors in patients with heart failure with reduced ejection fraction and advanced chronic kidney disease
Y Tamaki, H Yaku, E Yamamoto, N Ozasa, Y Inuzuka, S Enomoto, M Miyake, H Kondo, T Tamura, T Morimoto, Y Nakagawa, T Kato, T Kimura, K OnoAbstract
Background
Renin-angiotensin system inhibitor (RASi) represents a cornerstone of guideline-directed medical therapy for heart failure with reduced ejection fraction (HFrEF). However, RASi is often underutilized in patients with advanced chronic kidney disease (CKD) due to concerns regarding hyperkalemia and worsening renal function. Furthermore, as patients with advanced CKD were excluded from landmark clinical trials, the efficacy and safety of RASi in this specific population remains to be determined.
Purpose
To evaluate the association between RASi use and clinical outcomes in HFrEF patients with advanced CKD.
Methods
This was a post-hoc analysis of the Kyoto Congestive Heart Failure (KCHF) registry, a multicenter, prospective observational cohort study that enrolled consecutive patients hospitalized for acute decompensated heart failure in 19 hospitals in Japan between October 2014 and March 2016. Since angiotensin receptor-neprilysin inhibitors (ARNI) were not available in Japan during the study period, RASi was defined as either ACE inhibitor or ARB. The present study included patients with left ventricular ejection fraction (LVEF) of less than 40% and estimated glomerular filtration rate (eGFR) of less than 30ml/min/1.73m2 who were discharged alive. Patients were divided into two groups based on the prescription of RASi at discharge. The primary endpoint was a composite of all-cause death and heart failure hospitalization.
Results
Among 298 eligible patients, 147 (49.3%) were prescribed RASi at discharge. Baseline characteristics, including age, sex, LVEF, and BNP, were comparable between the two groups. The RASi group had slightly higher eGFR (21.4±6.5 vs. 19.7±6.4 mL/min/1.73 m², p=0.03) and more frequent use of beta-blockers (79.6% vs. 60.8%, p<0.001). The cumulative incidence of the primary endpoint one year after discharge was significantly lower in the RASi group (49.6% vs. 64.8%, p=0.001). After adjusting for potential confounders, RASi use remained independently associated with a reduced risk of the primary endpoint (adjusted hazard ratio 0.66; 95% confidence interval 0.47–0.93; p=0.02).
Conclusion
In real-world HFrEF patients with advanced CKD, the use of RASi at discharge was independently associated with a significantly lower risk of the composite of all-cause mortality and heart failure hospitalization.