Dapagliflozin, an sodium-glucose co-transporter 2 (SGLT2) inhibitor, appears to reduce the risk of heart failure (HF) worsening or cardiovascular (CV) death in patients with heart failure with reduced ejection fraction (HFrEF) regardless of their background therapy, according to the findings of a post-hoc analysis of the Dapagliflozin and Prevention of Adverse-outcomes in Heart Failure (DAPA-HF) trial. 

The phase 3 study found that, in patients with HFrEF, dapagliflozin decreased the incidence of the primary composite end point (HF worsening or CV death) compared with placebo. In their post-hoc analysis of the study, the authors aimed to determine whether this benefit was observed for all patients with HFrEF regardless of differing background therapies. 

In the analysis, the effect of dapagliflozin was examined in patients receiving a broad range of therapies (ie, diuretics, digoxin, mineralocorticoid receptor antagonists [MRA], sacubitril/valsartan, ivabradine, implanted cardioverter defibrillator device, cardiac resynchronization therapy). The effect was also evaluated based on angiotensin-converting enzyme inhibitor/angiotensin receptor blocker dose, beta-blocker (BB) dose, and MRA dose. 

Of the patients included in the study (N=4744), 84% were receiving a diuretic, 94% were receiving a renin-angiotensin system (RAS) blocker, and 96% were receiving a BB. “Overall, the dapagliflozin vs placebo hazard ratio (HR) was 0.74 [95% confidence interval (CI) 0.65–0.85] for the primary composite end point (P <.0001),” the authors reported. The effect of dapagliflozin was observed across all subgroups assessed, with HRs ranging from 0.57 to 0.86 for the primary end point; no significant treatment-by-subgroup interactions were observed. “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 3 of these treatments (P =.64),” the authors explained. 

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According to the findings of this post-hoc analysis, there appears to be a consistent clinical benefit with dapagliflozin in patients with HFrEF regardless of background HF therapy. These findings were presented during the virtual American College of Cardiology’s 69th Annual Scientific Session, together with the World Congress of Cardiology (ACC.20/WCC), and published in the European Heart Journal.


Docherty KR, Jhund PS, Inzucchi SE, et al; on behalf of the DAPA-HF Investigators and Committees. Effects of dapagliflozin in DAPA-HF according to background heart failure [published online March 28, 2020]. Eur Heart J. doi: 10.1093/eurheartj/ehaa183