Key result
Long-term use of dapagliflozin in 65-year-old patients with heart failure and LVEF >40% extended mean event-free survival by 2.3 years compared to placebo (95% CI: 0.9-3.8; P=0.002).
Why the study?
Expected lifetime benefits and event-free survival gains from long-term sodium-glucose cotransporter-2 inhibitor use in patients with heart failure with mildly reduced or preserved ejection fraction were unknown.
Does dapagliflozin improve event-free survival in patients with heart failure with mildly reduced or preserved ejection fraction?
RCT (n=6,263)
Randomized
Does dapagliflozin improve event-free survival in patients with heart failure with mildly reduced or preserved ejection fraction?
Mean Difference: 2.3 (95% CI 0.9–3.8)
Absolute Event Rate: 12.1% vs 9.7%
p-value: p=0.002
Dapagliflozin is projected to extend event-free survival by approximately 2 to 2.5 years in middle-aged and older patients with heart failure and LVEF >40%.
Supports long-term dapagliflozin initiation in HFmrEF/HFpEF; extends guideline recommendations with RCT-derived lifetime projections.
BACKGROUND: Recent guidelines support consideration of sodium-glucose cotransporter-2 inhibitors in the long-term management of heart failure (HF) with mildly reduced or preserved ejection fraction. Patients and clinicians may be interested in the expected lifetime benefits of sodium-glucose cotransporter-2 inhibitors in this population. OBJECTIVES: This study aimed to estimate event-free survival gains from long-term use of dapagliflozin in patients with HF with mildly reduced or preserved ejection fraction overall and in clinically relevant subgroups. METHODS: In this prespecified analysis of DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure), we applied validated nonparametric age-based methods to extrapolate potential gains in survival free from the primary endpoint (cardiovascular death or worsening HF event) from long-term use of dapagliflozin. Eligible participants had symptomatic HF, left ventricular ejection fraction >40%, elevated natriuretic peptide levels, and structural heart disease. For every year between the ages of 55 and 85 years, we estimated event-free survival using age at randomization rather than time from randomization as the time horizon. Residual lifespan free from a primary endpoint was estimated based on area under the survival curve in each arm. RESULTS: Among 6,263 participants, mean survival free from the primary endpoint for a 65-year-old participant was 12.1 years (95% CI: 11.0-13.2 years) with dapagliflozin and 9.7 years (95% CI: 8.8-10.7 years) with placebo, representing a 2.3-year (95% CI: 0.9-3.8 years) event-free survival gain (P = 0.002). Treatment gains in survival free from the primary endpoint ranged from 2.0 years (95% CI: -0.6 to 4.6 years) in a 55-year-old to 1.2 years (95% CI: -0.1 to 2.4 years) in a 75-year-old patient. Mean event-free survival was greater with dapagliflozin than with placebo across all 14 subgroups. CONCLUSIONS: Treatment with dapagliflozin is projected to extend event-free survival by up to 2.0 to 2.5 years among middle-aged and older individuals with HF with mildly reduced or preserved ejection fraction. (DELIVER [Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure]; NCT03619213).
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Vaduganathan et al. (2022) conducted an RCT in Heart failure with mildly reduced or preserved ejection fraction (n=6,263). Dapagliflozin vs. Placebo was evaluated on Cardiovascular death or worsening HF event (MD 2.3 years, 95% CI 0.9-3.8, p=0.002). Long-term use of dapagliflozin in 65-year-old patients with heart failure and LVEF >40% extended mean event-free survival by 2.3 years compared to placebo (95% CI: 0.9-3.8; P=0.002).
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