Heart failure with improved ejection fraction (HFimpEF) represents an understudied subgroup of heart failure patients who, despite LVEF improvement, face residual risks comparable to those with consistently higher LVEF (>40%). The prognostic implications of the degree of LVEF improvement and its impact on treatment response remain poorly understood. The DELIVER trial (NCT03619213) addresses this gap by evaluating dapagliflozin, a sodium-glucose cotransporter 2 inhibitor, in patients with heart failure and LVEF >40%, including those with HFimpEF. This study explores whether the extent of LVEF improvement influences clinical outcomes and the therapeutic benefits of dapagliflozin.
The DELIVER trial randomized 6,263 patients to dapagliflozin or placebo, with 1,151 (18%) classified as having HFimpEF. These patients were stratified by baseline LVEF into three groups: ≤49% (54%), 50%-59% (29%), and ≥60% (17%). The primary outcome was a composite of worsening heart failure or cardiovascular death, assessed over a median follow-up of 2.3 years. The trial examined whether the degree of LVEF improvement modified dapagliflozin’s efficacy, alongside evaluating safety across these LVEF subgroups.
Results showed that primary outcome rates (per 100 person-years) in HFimpEF versus patients with consistently LVEF >40% were 9.9 vs 10.5 (≤49%), 6.7 vs 8.4 (50%-59%), and 9.3 vs 7.5 (≥60%), indicating comparable residual risks. Dapagliflozin reduced the risk of the primary outcome consistently across all LVEF groups, with no significant interaction (P = 0.19), suggesting that the degree of LVEF improvement did not alter its therapeutic effect. The drug was also safe across these subgroups, with no notable differences in adverse events.
These findings highlight dapagliflozin’s consistent efficacy and safety in HFimpEF, regardless of achieved LVEF, including in patients reaching LVEF ≥60% who still face significant clinical risks. This supports the broader application of dapagliflozin in heart failure management, emphasizing its role in reducing worsening heart failure and cardiovascular death across diverse LVEF profiles. Future research should further explore long-term outcomes and optimal management strategies for HFimpEF to address ongoing residual risks.
