Abstract
BACKGROUND: Renin-angiotensin system (RAS) inhibition with high-dose (versus low-dose) angiotensin-converting inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) is associated with a lower risk of kidney failure in patients with heart failure. We examined whether this association varies between ACEIs and ARBs. METHODS: From 300,361 Veterans with heart failure without baseline kidney failure initiated on ACEIs (n = 256,224) or ARBs (n = 44,137), we assembled a propensity score-matched cohort of 88,178 patients while remaining blinded to study outcomes. Hazard ratio (95% CI) for 5-year kidney failure in patients in the ARB group was estimated. Kidney failure was defined as receipt of kidney replacement therapy or persistent drop in baseline estimated glomerular filtration rate (eGFR) to <15 mL/min/1.73m(2). RESULTS: Matched patients had mean age 71 years, ejection fraction 44%, eGFR 70 mL/min/1.73m(2), 97% were male, 18% African American, 23% received ACEIs or ARBs in high doses, and were balanced on 77 baseline characteristics. Kidney failure occurred in 4.4% (1961/44,089) and 5.4% (2389/44,089) of the patients in the ACEI and ARB groups, respectively. When accounted for the competing risk of death, patients in the ARB group had a 20% (95% CI, 13-28%) higher risk of kidney failure, which was similar in low-dose and high-dose subgroups. The associated risk of death was 5% (95% CI, 3-7%) lower in the ARB group, which was only significant in the low-dose group (7% vs 0%; interaction P, .007). CONCLUSION: In patients with heart failure, ARBs (vs. ACEIs) are associated with a higher risk of incident kidney failure. These findings need to be confirmed in future clinical trials.