The phase 3 DELIVER trial (NCT03619213) aimed to determine whether dapagliflozin would decrease cardiovascular morbidity and mortality in patients with HFmrEF/HFpEF, a group for whom limited therapies are currently available1. At last year’s ESC Congress, the only other large trial in this population, EMPEROR-Preserved, reported a reduction in cardiovascular death or heart failure hospitalisation for patients treated with empagliflozin2. Previously, dapagliflozin has been shown to be effective in heart failure patients with reduced ejection fraction3. According to Prof. Scott Solomon (Brigham and Women's Hospital, Harvard Medical School, MA, USA), DELIVER “was the largest and most inclusive trial” in this vulnerable patient cohort.
DELIVER was a double-blind, placebo-controlled trial which randomised patients (n=6,263) with symptomatic HF with an ejection fraction >40%, including 18% of the patients whose ejection fraction was previously ≤40%, to either dapagliflozin (10 mg once daily) or placebo. The primary endpoint was a composite of cardiovascular death or worsening heart failure.
With a median follow-up of 2.3 years, primary outcome events occurred in 16.4% of those in the dapagliflozin arm compared with 19.5% in the placebo group (HR 0.82; 95% CI 0.73–0.92; P=0.008). There was a discontinuation rate of 14% in both arms, and a total of 29% was lost to follow-up.
Analysing individual components of the primary endpoint showed that worsening heart failure occurred in 11.8% in the dapagliflozin group versus 14.5% in the placebo group (HR 0.79; 95% CI 0.69–0.91; P=0.001). However, cardiovascular death was not different between the arms, occurring in 7.4% and 8.3% of patients, respectively (HR 0.88; 95% CI 0.74–1.05; P=0.17). Key secondary endpoints also favoured dapagliflozin compared with placebo, including total heart failure hospitalisations and cardiovascular death (rate ratio 0.77; 95% CI 0.67–0.89), and total symptom burden, assessed using the Kansas City Cardiomyopathy Questionnaire (KCCQ) (mean difference in the KCCQ total symptom score 2.4; 95% CI 1.6–3.2; P<0.001).
Prof. Solomon said: “We found that dapagliflozin significantly reduced the primary composite endpoint by 18%, with numerically lower rates of all components of the primary endpoint. These benefits were consistent across prespecified subgroups, with similar benefits in patients with ejection fraction at, below, or above 60%, those with heart failure with improved ejection fraction, as well as in patients who were hospitalised recently, and was accompanied by improvement in symptoms.” The data provides further evidence to support the use of an SGLT2 inhibitor as foundational therapy for heart failure patients, regardless of care situation or ejection fraction.