Dapagliflozin DELIVERs for HFmrEF/HFpEF

The SGLT2 inhibitor dapagliflozin reduced the risk of cardiovascular death or worsening heart failure in heart failure patients with mildly reduced and preserved ejection fraction (HFmrEF/HFpEF), in the primary results of the DELIVER trial.

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 available [1]. At last year’s ESC Congress, the only other large trial in this population, EMPEROR-Preserved, reported a reduction in cardiovascular death or HF hospitalisation for patients treated with empagliflozin [2]. Previously, dapagliflozin has been shown to be effective in HF patients with reduced EF [3]. 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 EF >40%, including 18% of the patients whose EF was previously ≤40%, to either dapagliflozin (10 mg once daily) or placebo. The primary endpoint was a composite of cardiovascular death or worsening HF.

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). Analysing individual components of the primary endpoint showed that worsening HF 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, see Figure). However, cardiovascular death was not significantly different between the arms, occurring in 7.4% and 8.3% of participants, respectively (HR 0.88; 95% CI 0.74–1.05; P=0.17). Key secondary endpoints also favoured dapagliflozin compared with placebo, including total HF 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).

Figure: Components of DELIVER’s primary endpoint, full population [1]



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 EF at, below, or above 60%, those with HF with improved EF, 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 HF patients, regardless of care situation or EF.

1. Solomon S, et al. DELIVER - Dapagliflozin in Heart Failure with Mildly Reduced and Preserved Ejection Fraction. Hot Line Session 4, ESC Congress 2022, Barcelona, Spain, 26–29 August.
2. Anker SD, et al. N Engl J Med. 2021;385(16):1451–1461.
3. Wiviott SD, et al. N Engl J Med. 2019;380:347–357.

 

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Posted on 27 October 202227 October 2022