Lower Risk of Death and Kidney Failure Associated with Higher Target (vs Below-Target) Doses of RAS Inhibitors in...

Renin-angiotensin system (RAS) inhibitors at higher target doses reduce the risk of death in patients with heart failure with reduced ejection fraction (HFrEF). Less is known about their effectiveness in octogenarians, the examination of which was the objective of this study.

Of the 32,964 veterans ≥ 80 years with HFrEF (ejection fraction ≤ 40%) receiving RAS inhibitors, 6655 received them at target doses. Using propensity scores for the receipts of target-dose, calculated for each of the 32,964 patients, we assembled a matched cohort of 13,284 patients balanced on 66 baseline characteristics. Hazard ratios (95% CI) for 5-year mortality and kidney failure associated with target (vs below-target) dose RAS inhibitor use were estimated in the matched cohort. Kidney failure was defined as receipt of kidney replacement therapy or estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73m² measured twice >30 days apart.

Patients had mean (±SD) age 84.5 (±3.4) years, EF 31.3 (±8.2) %, and eGFR 58.5 (±18.2) mL/min/1.73m². All-cause mortality occurred in 71.2% and 69.5% of matched patients in below-target and target dose RAS inhibitor groups, respectively (HR associated with target-dose RAS inhibitor, 0.95; 95% CI, 0.91-0.99; P = .009). Respective rates for kidney failure were 1.8% and 1.5%, with a trend toward a lower risk in the target-dose group (HR, 0.80; 95% CI, 0.61-1.04; P = .094). Consequently, there was a lower risk of the composite endpoint of kidney failure or death (HR, 0.94; 95% CI, 0.91-0.98; P = .004).

These findings provide evidence that in octogenarians with HFrEF, the use of RAS inhibitors at higher target (vs below-target) doses is associated with lower risks of death and kidney failure.