On August 27, AstraZeneca updated the analysis results of the Phase III DAPA-HF and DELIVER studies, compared with placebo, dapagliflozin (brand name: Farxiga) can significantly reduce the mortality rate of people with complete heart failure , the first heart failure drug to achieve a survival benefit across the entire ejection fraction range. The latest results were presented at the 2022 ESC Congress (annual meeting of the European Society of Cardiology) and published simultaneously in Nature Medicine and the New England Journal of Medicine.
Heart failure (HF) is a long-term chronic disease, and almost all cardiovascular diseases eventually lead to HF, which worsens with age. HF can be divided into the following categories according to left ventricular ejection fraction (LVEF): reduced ejection fraction (HFrEF, LVEF ≤ 40%), mildly reduced ejection fraction (HFmrEF, LVEF 41-49%) and Preserved blood fraction (HFpEF, LVEF ≥ 50%). Approximately 50% of HF patients have HFmrEF or HFpEF, and treatment options for these groups are limited.
Dapagliflozin is a first-in-class sodium-glucose co-transporter 2 (SGLT2) inhibitor that needs to be taken orally once daily. It has been approved in the United States for 3 indications, including type 2 diabetes, HFrEF and chronic kidney disease. In March 2017, the product was launched in China for the treatment of adult patients with type 2 diabetes; in February 2021, it was expanded to new indications for the treatment of adult patients with HFrEF.
DAPA-HF and DELIVER are two randomized, double-blind, placebo-controlled Phase III trials, the former designed to evaluate the effect of dapagliflozin on heart failure worsening or cardiovascular death in patients with HFrEF, and the latter in patients with HFmrEF or HFpEF. test in. The two trials included a total of 11,007 patients, covering the whole heart failure population, and the primary composite endpoint was time to first occurrence of heart failure worsening or cardiovascular death.
The DELIVER results showed that during a median follow-up of 2.3 years, 16.4% (512 patients) of patients in the dapagliflozin group had a primary composite endpoint event compared with 19.5% (610 patients) in the placebo group. Dapagliflozin reduced the incidence of the primary composite endpoint by 18% (p<0.001), with some reduction in all component events.
A pooled analysis from two trials showed that, during a median follow-up of 22 months, dapagliflozin reduced the risk of cardiovascular death by 14% (p=0.01, absolute risk reduction ARR 1.5%) and the risk of death from any cause 10% (p=0.03, ARR 1.5%), a 29% (p < 0.001, ARR 6%) reduction in overall hospitalization rates (including first and repeat) for HF, and death from cardiovascular causes, myocardial infarction, or stroke The combined number of people decreased by 10% (p=0.045, ARR 1.3%).
Mene Pangalos, Executive Vice President, Biopharmaceuticals R&D, AstraZeneca, said: “Heart failure remains one of the leading causes of death globally, with an unmet need for approximately 64 million patients. This analysis shows that dapagliflozin has the ability to treat patients across the left ventricular ejection fraction spectrum, and reduce the risk of cardiovascular death.”