Effects of dapagliflozin in DAPA-HF according to background heart failure therapy

Docherty, K. F. et al. (2020) Effects of dapagliflozin in DAPA-HF according to background heart failure therapy. European Heart Journal, 41(25), pp. 2379-2392. (doi: 10.1093/eurheartj/ehaa183) (PMID:32221582) (PMCID:PMC7327533)

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Abstract

Aims In the DAPA-HF trial, the SGLT2 inhibitor dapagliflozin reduced the risk of worsening heart failure (HF) and death in patients with HF and reduced ejection fraction. We examined whether this benefit was consistent in relation to background HF therapy. Methods and results In this post hoc analysis, we examined the effect of study treatment in the following yes/no subgroups: diuretic, digoxin, mineralocorticoid receptor antagonist (MRA), sacubitril/valsartan, ivabradine, implanted cardioverter-defibrillating (ICD) device, and cardiac resynchronization therapy. We also examined the effect of study drug according to angiotensin-converting enzyme inhibitor/angiotensin receptor blocker dose, beta-blocker (BB) dose, and MRA (≥50% and <50% of target dose). We analysed the primary composite endpoint of cardiovascular death or a worsening HF event. Most randomized patients (n = 4744) were treated with a diuretic (84%), renin–angiotensin system (RAS) blocker (94%), and BB (96%); 52% of those taking a BB and 38% taking a RAS blocker were treated with ≥50% of the recommended dose. Overall, the dapagliflozin vs. placebo hazard ratio (HR) was 0.74 [95% confidence interval (CI) 0.65–0.85] for the primary composite endpoint (P < 0.0001). The effect of dapagliflozin was consistent across all subgroups examined: the HR ranged from 0.57 to 0.86 for primary endpoint, with no significant randomized treatment-by-subgroup interaction. For example, the HR in patients taking a RAS blocker, BB, and MRA at baseline was 0.72 (95% CI 0.61–0.86) compared with 0.77 (95% CI 0.63–0.94) in those not on all three of these treatments (P-interaction 0.64). Conclusion The benefit of dapagliflozin was consistent regardless of background therapy for HF.

Item Type:Articles
Additional Information:The study was funded by AstraZeneca. J.J.V.McM. is supported by a British Heart Foundation Centre of Research Excellence Grant RE/18/6/ 34217.
Keywords:Cardiology and cardiovascular medicine.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Docherty, Dr Kieran and Jhund, Dr Pardeep and McMurray, Professor John
Authors: Docherty, K. F., Jhund, P. S., Inzucchi, S. E., Køber, L., Kosiborod, M. N., Martinez, F. A., Ponikowski, P., DeMets, D. L., Sabatine, M. S., Bengtsson, O., Sjöstrand, M., Langkilde, A. M., Desai, A. S., Diez, M., Howlett, J. G., Katova, T., Ljungman, C. E. A., O’Meara, E., Petrie, M. C., Schou, M., Verma, S., Vinh, P. N., Solomon, S. D., and McMurray, J. J.V.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:European Heart Journal
Publisher:Oxford University Press (OUP)
ISSN:0195-668X
ISSN (Online):1522-9645
Published Online:28 March 2020
Copyright Holders:Copyright © 2020 The Authors
First Published:First published in European Heart Journal 41(25):2379–2392
Publisher Policy:Reproduced under a Creative Commons Licence

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
303944BHF Centre of ExcellenceRhian TouyzBritish Heart Foundation (BHF)RE/18/6/34217CAMS - Cardiovascular Science