Abstract
BACKGROUND: Renin-angiotensin system (RAS) inhibitors reduce risk of kidney failure in patients with chronic kidney disease, but worsen kidney function in heart failure patients, especially in those with chronic kidney disease. Less is known about risk of kidney failure in heart failure patients receiving RAS inhibitors. METHODS: We used propensity score matching for outcome-blinded assembly of 168,860 Veterans with heart failure phenotyped by artificial intelligence who were balanced on 77 baseline characteristics and initiated on RAS inhibitors. Hazard ratio (95% confidence interval [CI]) for 5-year kidney failure in high-dose (vs low-dose) RAS inhibitor group was estimated, accounting for competing risk of death. Kidney failure was defined as kidney replacement therapy or estimated glomerular filtration rate (eGFR) rate <15 mL/min/1.73 m(2). RESULTS: New-onset kidney failure occurred in 4.1% (3455/84,430) and 3.5% (2966/84,430) of patients in low-dose and high-dose RAS inhibitor groups, respectively (hazard ratio, 0.85; 95% CI, 0.81-0.89). Respective hazard ratios (95% CIs) in eGFR rate subgroups ≥60, 45-59, and 15-44 mL/min/1.73 m(2) were 1.21 (1.08-1.36), 0.93 (0.82-1.05), and 0.82 (0.77-0.87). The association was similar across ejection fraction subgroups. There was a lower risk of death in the subgroup with ejection fraction ≤40%. CONCLUSIONS: Patients with heart failure receiving high-dose (vs low-dose) RAS inhibitors had a lower associated risk of kidney failure, which was driven by the subgroup with chronic kidney disease. This new information may help to inform future guideline recommendations and clinical practice regarding RAS inhibitor use in these patients. Future studies need to examine this association in those with normal kidney function.