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

Mo-Kyung Sin; Richard M Allman; Charles Faselis; Wilbert S Aronow; Cynthia J Brown; Phillip H Lam; Wen-Chih Wu; Qing Zeng-Treitler; Samir S Patel; Venkatesh K Raman; Sijian Zhang; Helen M Sheriff; Charity J Morgan; Paul A Heidenreich; Gregg C Fonarow; Ali Ahmed

doi:10.1016/j.amjmed.2024.10.019

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

Am J Med. 2024 Nov 12:S0002-9343(24)00710-1. doi: 10.1016/j.amjmed.2024.10.019. Online ahead of print.

Authors

Mo-Kyung Sin¹, Richard M Allman², Charles Faselis³, Wilbert S Aronow⁴, Cynthia J Brown⁵, Phillip H Lam⁶, Wen-Chih Wu⁷, Qing Zeng-Treitler⁸, Samir S Patel⁸, Venkatesh K Raman⁹, Sijian Zhang¹⁰, Helen M Sheriff⁸, Charity J Morgan¹¹, Paul A Heidenreich¹², Gregg C Fonarow¹³, Ali Ahmed¹⁴

Affiliations

¹ College of Nursing, Seattle University, Seattle, WA.
² Department of Medicine, George Washington University, Washington, DC; Department of Medicine, University of Alabama at Birmingham, Birmingham, AL; Department of Medicine, Wake Forest University, Winston-Salem, NC.
³ Department of Medicine, George Washington University, Washington, DC; Department of Medicine, Veterans Affairs Medical Center, Washington, DC; Department of Medicine, Uniformed Services University, Washington, DC.
⁴ Department of Medicine, Westchester Medical Center, Valhalla, NY; Department of Medicine, New York Medical College, Valhalla, NY.
⁵ Department of Medicine, Louisiana State University, New Orleans, LA.
⁶ Department of Medicine, Georgetown University, Washington, DC; Department of Medicine, Medstar Washington Hospital Center, Washington, DC.
⁷ Department of Medicine, Veterans Affairs Medical Center, Providence, RI; Department of Medicine, Brown University, Providence, RI.
⁸ Department of Medicine, George Washington University, Washington, DC; Department of Medicine, Westchester Medical Center, Valhalla, NY.
⁹ Department of Medicine, Westchester Medical Center, Valhalla, NY; Department of Medicine, Georgetown University, Washington, DC.
¹⁰ Department of Medicine, Westchester Medical Center, Valhalla, NY.
¹¹ Department of Medicine, Westchester Medical Center, Valhalla, NY; Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL.
¹² Department of Medicine, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA; Department of Medicine, Stanford University, Stanford, CA.
¹³ Department of Medicine, University of California, Los Angeles, CA.
¹⁴ Department of Medicine, George Washington University, Washington, DC; Department of Medicine, Westchester Medical Center, Valhalla, NY; Department of Medicine, Georgetown University, Washington, DC. Electronic address: ali.ahmed@va.gov.

PMID: 39551174
DOI: 10.1016/j.amjmed.2024.10.019

Abstract

Background: Renin-angiotensin system inhibitors (RASIs) 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.

Methods: Of 32,964 Veterans ≥80 years with HFrEF (ejection fraction ≤40%) receiving RASIs, 6655 received target-dose. Using propensity scores for target-dose, calculated for each of 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 RASI 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.

Results: 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 RASI groups, respectively (HR associated with target-dose RASI, 0.95; 95% CI, 0.91-0.99; p=0.009). 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=0.094). 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=0.004).

Conclusions: These findings provide evidence that in octogenarians with HFrEF, the use of RASIs in higher target (vs. below-target) doses was associated with lower risks of death and kidney failure.

Keywords: HFrEF; RAS Inhibitors; death; kidney failure; octogenarians; target dose.