Renin-Angiotensin Inhibition and Outcomes in HFrEF and Advanced Kidney Disease

Samir Patel; Phillip H Lam; Evangelos I Kanonidis; Amiya A Ahmed; Venkatesh K Raman; Wen-Chih Wu; Patrick Rossignol; Cherinne Arundel; Charles Faselis; Ioannis E Kanonidis; Prakash Deedwania; Richard M Allman; Farooq H Sheikh; Gregg C Fonarow; Bertram Pitt; Ali Ahmed

doi:10.1016/j.amjmed.2023.03.017

Renin-Angiotensin Inhibition and Outcomes in HFrEF and Advanced Kidney Disease

Am J Med. 2023 Jul;136(7):677-686. doi: 10.1016/j.amjmed.2023.03.017. Epub 2023 Apr 3.

Authors

Samir Patel¹, Phillip H Lam², Evangelos I Kanonidis³, Amiya A Ahmed⁴, Venkatesh K Raman⁵, Wen-Chih Wu⁶, Patrick Rossignol⁷, Cherinne Arundel⁸, Charles Faselis⁹, Ioannis E Kanonidis¹⁰, Prakash Deedwania¹¹, Richard M Allman¹², Farooq H Sheikh¹³, Gregg C Fonarow¹⁴, Bertram Pitt¹⁵, Ali Ahmed¹⁶

Affiliations

¹ Veterans Affairs Medical Center, Washington, DC; George Washington University, Washington, DC.
² Veterans Affairs Medical Center, Washington, DC; Georgetown University, Washington, DC; MedStar Washington Hospital Center, Washington, DC.
³ Democritus University of Thrace, Alexandroupoli, Greece.
⁴ University of Maryland, Baltimore; Yale University, New Haven, Conn.
⁵ Veterans Affairs Medical Center, Washington, DC; Georgetown University, Washington, DC.
⁶ Veterans Affairs Medical Center, Providence, RI; Brown University, Providence, RI.
⁷ University of Lorraine, Nancy, France and Princess Grace Hospital, Monaco.
⁸ Veterans Affairs Medical Center, Washington, DC; George Washington University, Washington, DC; Georgetown University, Washington, DC.
⁹ Veterans Affairs Medical Center, Washington, DC; George Washington University, Washington, DC; Uniformed Services University, Washington, DC.
¹⁰ Aristotle University, Thessaloniki, Greece.
¹¹ Veterans Affairs Medical Center, Washington, DC; University of California, San Francisco.
¹² George Washington University, Washington, DC; University of Alabama at Birmingham.
¹³ Georgetown University, Washington, DC; MedStar Washington Hospital Center, Washington, DC.
¹⁴ University of California, Los Angeles.
¹⁵ University of Michigan, Ann Arbor.
¹⁶ Veterans Affairs Medical Center, Washington, DC; George Washington University, Washington, DC; Georgetown University, Washington, DC. Electronic address: ali.ahmed@va.gov.

PMID: 37019372
PMCID: PMC10466279 (available on 2024-07-01)
DOI: 10.1016/j.amjmed.2023.03.017

Abstract

Background: Renin-angiotensin system inhibitors improve outcomes in patients with heart failure with reduced ejection fraction (HFrEF). However, less is known about their effectiveness in patients with HFrEF and advanced kidney disease.

Methods: In the Medicare-linked Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF), 1582 patients with HFrEF (ejection fraction ≤40%) had advanced kidney disease (estimated glomerular filtration rate <30 mL/min/1.73 m²). Of these, 829 were not receiving angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) prior to admission, of whom 214 were initiated on these drugs prior to discharge. We calculated propensity scores for receipt of these drugs for each of the 829 patients and assembled a matched cohort of 388 patients, balanced on 47 baseline characteristics (mean age 78 years; 52% women; 10% African American; 73% receiving beta-blockers). Hazard ratios (HR) and 95% confidence intervals (CI) were estimated comparing 2-year outcomes in 194 patients initiated on ACE inhibitors or ARBs to 194 patients not initiated on those drugs.

Results: The combined endpoint of heart failure readmission or all-cause mortality occurred in 79% and 84% of patients initiated and not initiated on ACE inhibitors or ARBs, respectively (HR associated with initiation, 0.79; 95% CI, 0.63-0.98). Respective HRs (95% CI) for the individual endpoints of - Respective HRs (95% CI) for the individual endpoints of all-cause mortality and heart failure readmission were 0.81 (0.63-1.03) and 0.63 (0.47-0.85).

Conclusions: The findings from our study add new information to the body of cumulative evidence that suggest that renin-angiotensin system inhibitors may improve clinical outcomes in patients with HFrEF and advanced kidney disease. These hypothesis-generating findings need to be replicated in contemporary patients.

Keywords: Advanced kidney disease; Heart failure; Hospitalization; Mortality; Renin-angiotensin system inhibitors.

Published by Elsevier Inc.

Publication types

Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Angiotensin Receptor Antagonists / therapeutic use
Angiotensin-Converting Enzyme Inhibitors / therapeutic use
Angiotensins / therapeutic use
Female
Heart Failure* / drug therapy
Humans
Kidney Diseases* / drug therapy
Male
Medicare
Renin
Stroke Volume
United States

Substances

Renin
Angiotensins
Angiotensin-Converting Enzyme Inhibitors
Angiotensin Receptor Antagonists

Abstract

Publication types

MeSH terms

Substances

Grants and funding