Introduction
Sodium glucose contransporter-2 (SGLT2) inhibitors are strongly recommended in patients with chronic heart failure and reduced ejection fraction (HFrEF). Recent studies have also hinted at extending the benefits of SGLT2-inhibitors to all HF patients, irrespective of their left ventricular EF (LVEF).
Aim
The Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure (DELIVER) trial determined whether Dapagliflozin would reduce the risk of worsening HF or cardiovascular (CV) death among patients with a mildly reduced or preserved EF
Patient Profile
-
Patients (age ≥40 years) with chronic HF and an LVEF >40% with or without type-2 diabetes mellitus (T2DM) (n=6263)
-
All patients had stabilized HF at the time of enrollment in the study with an evidence of structural heart disease and elevated natriuretic peptide level
Methods
Study Design
-
A phase III, international, multicenter, parallel-group, event-driven, double-blind, randomized, controlled trial
Treatment Strategy
-
Patients were randomized to receive Dapagliflozin 10 mg once daily (n=3131) or placebo (n=3132)
Outcomes
Primary Outcome
-
A composite of worsening HF (defined as either an unplanned hospitalization for HF or an urgent visit for HF, or CV death)
Secondary Outcomes
-
Total number of worsening HF events and CV deaths
-
Change from baseline to 8 months in the total symptom score on the Kansas City Cardiomyopathy Questionnaire (KCCQ; scores range from 0 to 100, with higher scores indicating fewer symptoms and physical limitations)
-
Incidence of CV death, and death from any cause
Follow-up
-
Median duration: 2.3 years
Results
-
Fewer patients treated with Dapagliflozin vs. placebo experienced the primary composite outcome. Dapagliflozin vs. placebo was associated with a significant 18% reduction in the risk of primary outcome [Hazard ratio (HR): 0.82; p<0.001] (Fig 1).
-
Effect of Dapagliflozin was similar for patients with an LVEF <60% and the overall population.
-
Patients treated with Dapagliflozin vs. those treated with placebo had a significant 23% reduction in the risk of CV death and first and recurrent worsening HF events (HR: 0.77; p<0.001). Benefits of Dapagliflozin were equally evident in patients with LVEF <60%.
-
With respect to individual component of the primary outcome for the overall population and for patients with LVEF<60%, Dapagliflozin reduced the incidence of worsening HF by 21% (HR: 0.79; 95% CI, 0.69 to 0.91), of CV death by 12% (HR: 0.88; 95% CI, 0.74 to 1.05), and of death from any cause by 6% (HR: 0.94; 95% CI, 0.83 to 1.07).
-
Patients treated with Dapagliflozin vs. placebo had a greater improvement in the KCCQ total symptom score for HF symptoms from baseline to 8 months (mean placebo-corrected difference between baseline and month 8 among survivors, 2.4 points; 95% CI, 1.5 to 3.4).
-
Benefits of Dapagliflozin remained consistent irrespective of presence or absence T2DM.
-
There was no increased incidence of adverse events (AEs) or treatment discontinuation due to AE with Dapagliflozin vs. placebo.
Conclusions
-
Among patients with HF and a mildly reduced or preserved ejection fraction, Dapagliflozin lowered the risk of the primary composite outcome, worsening HF events and CV deaths, vs. placebo.
-
Dapagliflozin also lowered the symptom burden, without any increase in the incidence of AEs.
-
Findings were consistent across prespecified subgroups, including those defined as per the LVEF.
-
SGLT2 inhibitors represent an essential therapy segment in HF patients, regardless of the LVEF or presence or absence of T2DM.
N Engl J Med 2022;387:1089-98.