Association of carbohydrate antigen 125 on the response to dapagliflozin in patients with heart failure

Docherty, K. F. et al. (2023) Association of carbohydrate antigen 125 on the response to dapagliflozin in patients with heart failure. Journal of the American College of Cardiology, 82(2), pp. 142-157. (doi: 10.1016/j.jacc.2023.05.011) (PMID:37407113)

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Abstract

Background: Elevated circulating carbohydrate antigen 125 (CA125) is a marker of congestion and a predictor of outcomes in acute heart failure (HF). Less is known about CA125 in chronic ambulatory HF with reduced ejection fraction. Objectives: This study examined the association between baseline CA125 (and changes in CA125) and outcomes in patients with HF with reduced ejection fraction in the DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure; NCT03036124) trial and its relationship with the effect of dapagliflozin. Methods: The primary outcome was a composite of a first episode of worsening HF or cardiovascular death. CA125 was measured at baseline and 12 months following randomization. Results: Median baseline CA125 was 13.04 U/mL (IQR: 8.78-21.13 U/mL) in 3,123 of 4,774 patients with available data. Compared with CA125 ≤35 U/mL (upper limit of normal), patients with CA125 >35 U/mL were at a higher risk of the primary outcome (adjusted HR: 1.59; 95% CI: 1.29-1.96). The adjusted risks of the primary outcome relative to quartile 1 (Q1) (≤8.78 U/mL) were as follow: Q2, 8.79-13.04 U/mL (HR: 0.94; 95% CI: 0.71-1.24); Q3, 13.05-21.13 U/mL (HR: 1.22; 95% CI: 0.94-1.59); Q4, ≥21.14 U/mL (HR: 1.63; 95% CI: 1.28-2.09). The beneficial effect of dapagliflozin compared with placebo on the primary outcome was consistent whether CA125 was analyzed in quartiles (interaction P = 0.13) or as a continuous variable (interaction P = 0.75). The placebo-corrected relative change in CA125 at 12 months was −5.2% (95% CI: −10.6% to 0.5%; P = 0.07). Conclusions: In DAPA-HF, elevated CA125 levels were an independent predictor of the risk of worsening HF or cardiovascular death. Dapagliflozin reduced the risk of worsening HF or cardiovascular death regardless of baseline CA125.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McDowell, Dr Kirsty and Docherty, Dr Kieran and Jhund, Professor Pardeep and Welsh, Professor Paul and Kober, Professor Lars and Osmanska, Dr Joanna and Sattar, Professor Naveed and McMurray, Professor John
Authors: Docherty, K. F., McDowell, K., Welsh, P., Osmanska, J., Anand, I., de Boer, R. A., Køber, L., Kosiborod, M. N., Martinez, F. A., O’Meara, E., Ponikowski, P., Schou, M., Berg, D. D., Sabatine, M. S., Morrow, D. A., Jarolim, P., Hammarstedt, A., Sjöstrand, M., Langkilde, A. M., Solomon, S. D., Sattar, N., Jhund, P. S., and McMurray, J. J.V.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:Journal of the American College of Cardiology
Publisher:Elsevier
ISSN:0735-1097
ISSN (Online):1558-3597
Published Online:03 July 2023
Copyright Holders:Copyright © 2023 The Authors
First Published:First published in Journal of the American College of Cardiology 82(2): 142-157
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
303944BHF Centre of ExcellenceColin BerryBritish Heart Foundation (BHF)RE/18/6/34217SCMH - Cardiovascular & Metabolic Health