Worsening Renal Function and Outcome in Heart Failure Patients with Reduced and Preserved Ejection Fraction and the Impact of Angiotensin Receptor Blocker Treatment: Data from the CHARM-Study Programme
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Aims: We investigated the association between worsening renal function (WRF) that occurs during renin–angiotensin–aldosterone system inhibition initation and outcome in heart failure (HF) patients with preserved ejection fraction (HFPEF) and compared this with HF patients with reduced ejection fraction (HFREF). Methods and results: We examined changes in estimated glomerular filtration rate (GFR) and the relationship between WRF (defined as ≥26.5 µmol/L and ≥25% increase in serum creatinine from baseline to 6 weeks) and outcome, according to randomized treatment, in patients with HFREF (EF <45%; n = 1569) and HFPEF (EF ≥45%; n = 836) in the CHARM programme. The primary outcome was cardiovascular death or HF hospitalization. Estimated GFR decreased 9.0 ± 21 vs. 4.0 ± 21 mL/min/1.73 m2 with candesartan and placebo, respectively, and this was similar in HFREF and HFPEF. WRF developed more frequently with candesartan, 16% vs. 7%, P < 0.001, with similar findings in patients with HFREF and HFPEF. WRF was associated with a higher risk of the primary outcome: multivariable hazard ratio (HR) 1.26, 95% confidence interval 1.03–1.54, P = 0.022, in both treatment groups, and in both HFREF and HFPEF (P for interaction 0.98). In HFREF, WRF was mostly related to HF hospitalization, while in HFPEF, WRF seemed more associated with mortality. Conclusions: GFR decreased more and WRF was more common with candesartan compared with placebo, and this was similar in HFREF and HFPEF. WRF was associated with worse outcomes in HFREF and HFPEF. Although no formal interaction was present, the association between candesartan treatment, WRF, and type of clinical outcome was slightly different between HFREF and HFPEF.
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Previous studies have shown that worsening kidney function identified by even modest increases in creatinine (or equivalent reductions in eGFR) is associated with worse cardiovascular outcomes in patients with HFrEF.
“The reduced risk of doubling of creatinine concentration is notable, given that previous studies have shown that worsening kidney function identified by even modest increases in creatinine (or equivalent reductions in eGFR) are associated with worse cardiovascular outcomes in patients with HFrEF.3,17,18,22”
From Efficacy of Dapagliflozin on Renal Function and Outcomes in Patients With Heart Failure With Reduced Ejection Fraction: Results of DAPA-HF (2021) · cites this paper as [22]
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- Authors
- Damman, K., Solomon, S. D., Pfeffer, M. A., Swedberg, K., Yusuf, S., Young, J. B., Rouleau, J. L., Granger, C. B., & McMurray, J. J. V.
- Affiliations
- University Medical Center Groningen (NL)
- Brigham and Women's Hospital (US)
- University of Gothenburg (SE)
- Population Health Research Institute (CA)
- Cleveland Clinic (US)
- Université de Montréal (CA)
- Duke Medical Center (US)
- University of Glasgow (GB)
- Corresponding author
- Damman, Kevin
- ORCID
- Venue
- European Journal of Heart Failure
- Publisher
- Oxford University Press (OUP)
- Published
- 2016-07-18
- Volume
- 18
- Issue
- 12
- Pages
- 1508-1517
- ISSN
- 1388-9842 (ISSN-L)
- 1879-0844
- OpenAlex
- W2491534867
- Cited by
- 75
- References
- 25
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 10 · 2023: 5 · 2022: 9 · 2021: 6 · 2020: 8 · 2019: 7 · 2018: 11 · 2017: 8 · 2016: 4 · 2014: 1
- FWCI
- 8.26
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- European Journal of Heart Failure (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion)
- Research Bank (Australian Catholic University) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Funders
- Netherlands Heart Institute
- ESC Heart Failure Association Research Grant
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Keywords
- worsening renal function, heart failure, preserved ejection fraction, reduced ejection fraction, angiotensin receptor blockers, candesartan, renin-angiotensin-aldosterone system inhibition, estimated glomerular filtration rate, serum creatinine, cardiovascular mortality, heart failure hospitalization
- MeSH terms
- Aged, Benzimidazoles, Biphenyl Compounds, Creatinine, Female, Glomerular Filtration Rate, Heart Failure, Humans, Male, Middle Aged, Stroke Volume, Tetrazoles, Multivariate Analysis, Logistic Models, Proportional Hazards Models, Randomized Controlled Trials as Topic, Disease Progression, Renal Insufficiency, Angiotensin Receptor Antagonists
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