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 |
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| 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, Professor Pardeep and Petrie, Professor Mark and Kober, Professor Lars 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 > School of Cardiovascular & Metabolic Health |
| Journal Name: | European Heart Journal |
| Publisher: | Oxford University Press |
| 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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