Dapagliflozin significantly reduced the risk of cardiovascular (CV) death or worsening of heart failure (HF) in patients with HF and mildly reduced or preserved ejection fraction (HFpEF), according to detailed results from the phase 3 DELIVER trial.

The placebo-controlled, event-driven study (ClinicalTrials.gov Identifier: NCT03619213) included 6263 patients 40 years of age and older with HF and left ventricular ejection fraction (LVEF) of greater than 40%, with or without type 2 diabetes. Patients were randomly assigned 1:1 to receive dapagliflozin 10mg or placebo once daily, in addition to background therapy.

The primary composite endpoint was the time to first occurrence of CV death, hospitalization for HF or an urgent HF visit, in the full study population, as well as in patients with LVEF of less than 60%.

Over a median follow-up of 2.3 years, treatment with dapagliflozin reduced the composite outcome of CV death or worsening of HF by 18% compared with placebo (hazard ratio [HR], 0.82; 95% CI, 0.73-0.92; P <.001). Worsening HF occurred in 11.8% (n=368) of patients in the dapagliflozin arm and 14.5% (n=455) of patients in the placebo arm (HR, 0.79; 95% CI, 0.69-0.91); CV death occurred in 7.4% (n=231) of patients in the dapagliflozin arm and 8.3% (n=261) of patients in the placebo arm (HR, 0.88; 95% CI, 0.74-1.05). The findings were consistent among patients with LVEF of less than 60%, as well as among those with or without diabetes.

“These results from DELIVER are important for patients and clinical care as it shows that dapagliflozin is effective regardless of ejection fraction and therefore can be used as foundational therapy in all eligible patients with heart failure,” said Dr Scott Solomon, Professor of Medicine at Harvard Medical School and Brigham and Women’s Hospital and Principal Investigator of the DELIVER phase 3 trial. “Earlier heart failure with preserved ejection fraction trials have shown attenuation in the highest left ventricular ejection fraction but with dapagliflozin results are consistent across the ejection fraction range. The findings also reinforce most recent treatment guidelines, recommending earlier initiation of guideline-directed medical treatment and may support broader use of SGLT2 inhibitors in clinical practice.”

Additionally, a pooled analysis of data from the phase 3 DAPA-HF (ClinicalTrials.gov Identifier: NCT03036124) and DELIVER trials showed a significant reduction in CV death among HF patients treated with dapagliflozin, compared with placebo, irrespective of LVEF. Over a median follow-up of 22 months, dapagliflozin reduced the risk of CV death by 14% (absolute risk reduction [ARR] 1.5%; P =.01), death from any cause by 10% (ARR 1.5%; P =.03), total (first and repeat) hospitalization for HF by 29% (ARR 6%; P <.001), and the composite of death from CV causes, myocardial infarction, or stroke by 10% (ARR 1.3%; P =.045). 

Dapagliflozin is marketed under the brand name Farxiga and is currently approved to reduce risk of CV death and hospitalization for HF in adults with HF (NYHA Class II-IV) with reduced ejection fraction based on data from the DAPA-HF trial (ClinicalTrials.gov Identifier: NCT03036124).

It is also indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus, to reduce the risk of hospitalization for heart failure in adults with type 2 diabetes mellitus and established CV disease or multiple CV risk factors, and to reduce the risk of sustained eGFR decline, end‑stage kidney disease, CV death, and hospitalization for HF in adults with chronic kidney disease at risk of progression.

References

  1. Farxiga significantly reduced the risk of cardiovascular death or worsening of heart failure in patients with mildly reduced or preserved ejection fraction in DELIVER Phase III trial. News release. AstraZeneca. Accessed August 29, 2022. https://www.businesswire.com/news/home/20220826005408/en/FARXIGA-significantly-reduced-the-risk-of-cardiovascular-death-or-worsening-of-heart-failure-in-patients-with-mildly-reduced-or-preserved-ejection-fraction-in-DELIVER-Phase-III-trial
  2. Solomon S, McMurray JJ, Claggett B, et al. Dapagliflozin in heart failure with mildly reduced or preserved ejection fraction. N Engl J Med. Published online August 27, 2022. doi:10.1056/NEJMoa2206286
  3. New data show Farxiga significantly lowers the risk of cardiovascular death in patients with heart failure. News release. AstraZeneca. Accessed August 29, 2022. https://www.astrazeneca-us.com/content/az-us/media/press-releases/2022/new-data-show-farxiga-significantly-lowers-the-risk-of-cardiovascular-death-in-patients-with-heart-failure.html