March 28, 2020 — New data from a sub-analysis of the landmark Phase III DAPA-HF (Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure) trial showed that AstraZeneca’s dapagliflozin (Farxiga) reduced the incidence of the primary composite endpoint of heart failure (HF) worsening or cardiovascular (CV) death compared to placebo, in patients with heart failure with reduced ejection fraction (HFrEF), irrespective of their background therapy (i.e. other medications for heart failure).
Farxiga was evaluated in patients who were receiving a broad range of pharmacological treatments, device therapies and cardiac resynchronization therapy for HFrEF. A consistent reduction in the primary outcome was observed across all these treatment subgroups.
The results were made available at the American College of Cardiology (ACC) 2020 Scientific Session together with World Congress of Cardiology (ACC.20/WCC) and were published in the European Heart Journal.
Dapagliflozin is indicated as a monotherapy and as part of combination therapies to improve glycemic control in adults with type-2 diabetes (T2D). In the U.S. it is also approved to reduce the risk of hospitalization for HF in patients with T2D and established CV disease or multiple CV risk factors.
In January 2020, the U.S. Food and Drug Administration (FDA) accepted a supplemental New Drug Application (sNDA) and granted Priority Review for Farxiga to reduce the risk of CV death or the worsening of HF in adults with HFrEF with and without T2D. The Prescription Drug User Fee Act date, the FDA action date for this supplemental application, is scheduled for the second quarter of 2020.
Overview of the DAPA-HF Trial
DAPA-HF (Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure) is an international, multi-centre, parallel-group, randomized, double-blinded trial in patients with heart failure and reduced ejection fraction (LVEF ≤ 40 percent), with and without T2D, designed to evaluate the effect of dapagliflozin 10 mg, compared with placebo, given once daily in addition to standard of care. The primary composite endpoint was time to the first occurrence of a worsening heart failure event (hospitalization or equivalent event; i.e. an urgent heart failure visit), or cardiovascular death.
What is Dapagliflozin?
Dapagliflozin (Farxiga) is a first-in-class, oral once-daily SGLT2 inhibitor indicated in adults for the treatment of insufficiently controlled T2D as both monotherapy and as part of combination therapy as an adjunct to diet and exercise to improve glycemic control, with the additional benefits of weight loss and blood-pressure reduction. In the DECLARE CV outcomes trial in adults with T2D, dapagliflozin reduced the risk of the composite endpoint of hospitalization for HF or CV death versus placebo, when both were added to standard of care.
In the DAPA-HF trial, dapagliflozin on top of standard of care reduced both the incidence of cardiovascular death and the worsening of heart failure in patients with HFrEF, with and without T2D. Farxiga is also being investigated for patients with HF in the DELIVER (HFpEF) and DETERMINE (HFrEF and HFpEF) trials, as well as patients with chronic kidney disease (CKD) in the DAPA-CKD trial. Farxiga has a robust program of clinical trials that includes more than 35 completed and ongoing Phase IIb/III trials in more than 35,000 patients, as well as more than 2.5 million patient-years’ experience.
What is Heart Failure?
HF is a life-threatening disease in which the heart cannot pump enough blood around the body. It affects approximately 64 million people worldwide, at least half of whom have a reduced ejection fraction, and is a chronic and degenerative disease where half of patients will die within five years of diagnosis.[4,5] HF remains as fatal as some of the most common cancers in both men (prostate and bladder cancers) and women (breast cancers). It is the leading cause of hospitalization for those over the age of 65 and represents a significant clinical and economic burden.
Related DAPA-HF Trial Content:
1. Docherty KF et al. 2020 Consistent Benefit of Dapagliflozin According to Background Therapy in Patients with HFrEF: An Analysis of the DAPA-HF Trial. Presented at the American College of Cardiology’s 69th Annual Scientific Session Together with World Congress of Cardiology (ACC.20/WCC); 28 March – 30 March, Chicago.
2. Kieran F Docherty, Pardeep S Jhund, Silvio E Inzucchi, et al. Effects of dapagliflozin in DAPA-HF according to background heart failure therapy. European Heart Journal, ehaa183, https://doi.org/10.1093/eurheartj/ehaa183. Published onlin 28 March 2020.
6. Mamas, M. A., Sperrin, M., Watson, M. C., Coutts, A., et al. (2017). Do patients have worse outcomes in heart failure than in cancer? A primary care-based cohort study with 10-year follow-up in Scotland. European Journal of Heart Failure, 19(9), 1095-1104. https://doi.org/10.1002/ejhf.822.