Achieved Ejection Fraction and Effects of Dapagliflozin in Heart Failure With Improved Ejection Fraction

Background: Patients with heart failure with improved ejection fraction (HFimpEF) remain understudied and face residual risks comparable with those with a left ventricular ejection fraction (LVEF) consistently >40% (no prior heart failure with reduced ejection fraction). The implications of achieved LVEF after improvement on prognosis and treatment response remains unclear. 

Objectives: This study examines whether the degree of LVEF improvement influences prognosis and the therapeutic effects of dapagliflozin in HFimpEF. 

Methods: The DELIVER trial randomized patients with heart failure and LVEF >40% to dapagliflozin or placebo, including those with HFimpEF. In the HFimpEF subset, we examined the association between baseline LVEF (≤49% [reference group], 50%-59%, and ≥60%) and the primary outcome (worsening HF or cardiovascular death) and whether the degree of LVEF improvement modified the treatment response to dapagliflozin. 

Results: Of 6,263 participants, 1,151 (18%) had HFimpEF: 624 (54%), 328 (29%), and 199 (17%) had improved LVEF at baseline of ≤49%, 50%-59%, and ≥60%, respectively. Over a median follow-up of 2.3 years, primary outcome rates (per 100 person-years) in HFimpEF vs LVEF consistently >40% were 9.9 vs 10.5 (≤49%), 6.7 vs 8.4 (50%-59%), and 9.3 vs 7.5 (≥60%). Dapagliflozin safely and consistently reduced the risk of the primary outcome across LVEF groups (P for interaction = 0.19). 

Conclusions: In patients with HFimpEF, the efficacy and safety of dapagliflozin in reducing cardiovascular death or worsening HF events were consistent irrespective of the degree of LVEF improvement before enrollment, including in those who achieve an LVEF ≥60% who appear to face significant residual risks of clinical events.