Abstract
Background
Loop diuretics are the mainstay of congestion treatment in patients with heart failure (HF). We assessed the association between baseline loop diuretic use and outcome. We also compared the increment in risk related to diuretic dose with conventional prognostic enrichment criteria used in the EMPHASIS-HF trial, which included patients with systolic HF and mild symptoms, such as prior hospitalization and elevated natriuretic peptides.
Methods
Individual analyses were performed according to baseline loop diuretic usage (furosemide-equivalent dose > 40 mg, 1–40 mg, and no furosemide), and according to enrichment criteria adopted in the trial [i.e. recent hospitalization (< 30 days or 30 to 180 days prior to randomization) due to HF or other cardiovascular cause, or elevated natriuretic peptides]. The primary endpoint was a composite of cardiovascular death or HF hospitalization.
Results
Loop diuretic usage at baseline (HR for > 40 mg furosemide-equivalent dose = 3.16, 95% CI 2.43–4.11; HR for 1–40 mg = 2.06, 95% CI 1.60–2.65) was significantly associated with a higher risk for the primary endpoint in a stepwise manner when compared to no baseline loop diuretic usage. In contrast, the differences in outcome rates were more modest when using history of hospitalization and/or BNP: all HR ranged from 1 (reference, non-HF related CV hospitalization > 30 days) to 2.04 (HF hospitalization < 30 days). The effect of eplerenone on the primary endpoint was consistent across subgroups in both analyses (P for interaction ≥ 0.2 for all).
Conclusions
Loop diuretic usage (especially at doses > 40 mg) identified patients at higher risk than history of HF hospitalization and/or high BNP blood concentrations.
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Abbreviations
- HF:
-
Heart failure
- LVEF:
-
Left ventricular ejection fraction
- BNP:
-
B-type natriuretic peptide and
- NT-proBNP:
-
N-terminal pro–BNP
- EMPHASIS-HF:
-
Eplerenone in mild patients hospitalization and survival study in heart failure
- HFrEF:
-
HF with reduced ejection fraction
- HR:
-
Hazard ratio
- 95% CI:
-
95% Confidence interval
- CHARM:
-
Candesartan in heart failure: reduction in mortality and morbidity
- ReBIC:
-
Rede Brasileira de Estudos em Insuficiência Cardíaca
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Acknowledgements
The EMPHASIS HF trial was sponsored by Pfizer. SC, NG, PR, FZ are supported by the RHU Fight- HF, a public grant overseen by the French National Research Agency (ANR) as part of the second “Investissements d’Avenir” program (reference: ANR-15-RHUS-0004).
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Dr. Girerd received board fees from Novartis and honoraria from Servier. Dr. Rossignol received personal fees (consulting) from Novartis, Relypsa, AstraZeneca, Grünenthal, Stealth Peptides, Fresenius, Vifor Fresenius Medical Care Renal Pharma, Vifor, and CTMA; lecture fees from Bayer and CVRx; and is cofounder of CardioRenal. Dr Zannad received steering committte or advisory board fees from Amgen, AstraZeneca, Bayer, Boehringer, Boston Scientific, Cardior, CVRx, Janssen, Livanova, Merck, Mundipharma, Novartis, NovoNordisk and Vifor Fresenius. Dr Pitt received personal fees from Bayer, KDP pharmaceuticals, Astra Zeneca, Sanofi, Relypsa/Vifor, scPharmaceuticals, stealth peptides, tricida, personal fees from G3 pharmaceuticals. Dr McMurray received fees for his consulting or trial committee work with Abbvie, Amgen, AstraZeneca/Medimmune, Bayer, Bristol Myers Squibb, DalCor, GlaxoSmithKline, Merck, Novartis, Resverlogix, Sanofi-Aventis and Stealth Therapeutics. Dr Swedberg received personal fees from Novartis, AstraZeneca, Pfizer, and Novartis. Dr. Van Veldhuisen received board membership fees or travel expenses from Novartis, Corvia Medical, ARCA Biopharma and Johnson and Johnson. All other authors have no conflicts of interest to declare.
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Coiro, S., Girerd, N., McMurray, J.J.V. et al. Diuretic therapy as prognostic enrichment factor for clinical trials in patients with heart failure with reduced ejection fraction. Clin Res Cardiol 110, 1308–1320 (2021). https://doi.org/10.1007/s00392-021-01851-w
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DOI: https://doi.org/10.1007/s00392-021-01851-w