Dapagliflozin reduces combined risk of HF worsening or CV death in patients with HFmEF or HFpEF

07 Jun 2023

Sodium-glucose cotransporter 2 (SGLT2) inhibitors, such as dapagliflozin, are strongly recommended by clinical guidelines for the treatment of chronic heart failure (HF) with reduced ejection fraction (HFrEF).1 Recently, emerging data have suggested that the benefits of SGLT2 inhibitors may extend to HF patients with mildly reduced or preserved ejection fraction (HFmEF or HFpEF).2 In the DELIVER trial, dapagliflozin has demonstrated a significant reduction in the risk of HF worsening and cardiovascular (CV) death in patients with HFmEF and HFpEF, supporting its use in HF patients, regardless of the left ventricular ejection fraction (LVEF).3

SGLT2 inhibitors were originally used for the management of type 2 diabetes mellitus.4 Due to their diuretic effect, the drugs can decrease blood and interstitial fluid volume, thus lowering the preload and afterload of the heart and achieving a lower left ventricular end-diastolic volume and pressure.5 With that, SGLT2 inhibitors are believed to be able to elicit a therapeutic effect in heart failure.5 Previously, a number of randomized trials have demonstrated the clinical benefits of SGLT2 inhibitors in HFrEF, providing additional treatment options for patients.3 Yet, for patients with HFmEF or HFpEF, pharmacological treatment choices remain limited.

The DELIVER trial is a phase 3, double-blinded, multicenter randomized controlled trial which included 6,263 patients aged ≥40 years, with a stable heart failure of a left ventricular ejection fraction of >40%, structural heart disease and increased level of natriuretic peptide.3 These patients were randomly assigned to either the dapagliflozin (n=3,131) or placebo (n=3,132) group.3 The primary outcome was a composite of worsening HF (defined as either an unplanned hospitalization for HF or an urgent visit for HF) or CV death.3 Secondary outcomes included frequency of worsening HF events, CV deaths, death from any cause, and change in total symptom score based on the Kansas City Cardiomyopathy Questionnaire (KCCQ) at month 8.3

The primary outcome occurred in 16.4% (n=512) in the dapagliflozin and 19.5% (n=610) in the placebo group, demonstrating a significantly reduced risk with dapagliflozin of 18% vs. placebo (HR=0.82; 95% CI: 0.73-0.92; p<0.001).3 The frequencies of worsening HF events were also lower in the dapagliflozin group (11.8%) as compared to that in the placebo (14.5%) group (HR=0.79; 95% CI: 0.69-0.91).3 In addition, the number of first and recurrent HF worsening events and CV death was lower with the dapagliflozin group than that in the placebo group in the overall population (HR=0.77; 95% CI: 0.67-0.89; p<0.001), and a group of patients with LVEF <60% (RR=0.77; 95% CI=0.65-0.90; p=0.002).3

On the other hand, patients treated with dapagliflozin were found to have a lower symptom burden, shown by the improvement in total HF symptom score from baseline to month 8 when compared to the placebo group (Win ratio=1.11; 95% CI: 1.03-1.21; p=0.009).3 Overall, the results were comparable for patients with a LVEF ≥60% and those <60%.3 Likewise, the findings were consistent across prespecified subgroups, such as patients with or without diabetes.3 The occurrence of adverse events (AEs) is similar between the 2 study arms.3

In summary, the DELIVER trial demonstrated that dapagliflozin significantly reduces the risk of HF worsening and CV death and is associated with a lower HF symptom burden in patients with HFmEF and HFpEF.3  The findings support wider adoption of dapagliflozin for the treatment of HF patients, regardless of the LVEF.

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