Introduction and methods

Consistent benefit of dapagliflozin according to background therapy in patients with HFrEF: an analysis of the DAPA-HF trial

Presented at ACC.20 by Kieran Docherty (Glasgow, UK)

The DAPA-HF trial showed that the SGLT2 inhibitor dapagliflozin reduced the risk of CV death or worsening heart failure in patients with HFrEF, compared to placebo.

In DAPA-HF, patients with HFrEF (NYHA class II-IV, LVEF ≤40%, NT-proBNP ≥600 pg/ml [≥400 pg/ml if HF hospilization within ≤12 monts, ≥900 pg/ml if artrial fibrillation/flutter]) were randomized to receive either dapagliflozin (10 mg once daily, n=2373) or placebo (n=2371). The primary composite endpoint was first event of worsening HF (unplanned hospitalization or urgent visit requiring IV therapy for HF) or CV death. Dapagliflozin reduced the risk of the primary endpoint by 26% compared to placebo (HR 0.74, 95%CI 0.65-0.85).

This post-hoc analysis compared the effect of dapagliflozin with placebo in subgroups (containing >200 individuals) of patients treated with other background pharmacological and device therapies on the primary outcome. Yes/no groups that were analyzed were: diuretic, mineralocorticoid receptor antagonist (MRA), digoxin, sacubitril-valsartan, ivabradine, defibrillating device (implantable cardioverter-defibrillator [ICD] or cardiac resynchronization therapy plus defibrillator [CRT-D]) and CRT (CRT-P and CRT-D). The effect of dapagliflozin according to beta-blocker, RAS blocker and MRA dose at baseline, defined as ≥50% target dose and <50% of target dose, were also examined.

Main results

• The current analysis showed no modification in treatment effect on the primary endpoint, whether or not patients were taking diuretics, MRA, digoxin, sacubitril-valsartan or ivabradine.

• Similarly, no modification of treatment effect on the primary endpoint was found depending on whether patients were taking <50% or ≥50% of target dose of RAS blocker, beta-blocker or MRA.

• The treatment effect of dapagliflozin compared to placebo on the primary endpoint was also consistent in patients with or without an ICD or CRT.

Conclusion

This post-hoc analysis of the DAPA-HF trial showed a consistent benefit of dapagliflozin in reducing risk of the primary outcome compared to placebo, regardless of background drug and device therapy in patients with HFrEF.

• Our coverage of ACC.20 is based on the information provided during the congress –

The results were simultaneously published in Eur Heart J