Therapy Areas: Cardiovascular
Consistent Effects of Farxiga in Heart Failure Patients with Reduced Ejection Fraction Shown in New Analyses from Landmark Phase III DAPA-HF Trial
19 November 2019 - - British-Swedish pharmaceutical company AstraZeneca (OTC: AZNCF) released new data from five additional analyses of the landmark Phase III DAPA-HF trial, which showed that Farxiga (dapagliflozin) reduced the risk of the primary composite outcome of worsening heart failure, defined as hospitalization or an urgent visit, or death from cardiovascular causes versus placebo, when added to standard of care, the company said.
DAPA-HF is the first outcomes trial with an SGLT2 inhibitor investigating the treatment of HF in patients with reduced ejection fraction (HFrEF), with and without type 2 diabetes.
The new analyses showed the consistency of these results across patient subgroups with and without T2D, an early onset of effects, and improvement in patient-reported outcomes of HF-related health status.
These data were presented at the American Heart Association Scientific Sessions in Philadelphia.
Across all five analyses, Farxiga showed improvements versus placebo in the worsening or progression of the disease and improved patient-reported symptoms and quality of life.
The Dapagliflozin and Prevention of Adverse-outcomes in Heart Failure Trial (DAPA-HF): Results in Nondiabetic Patients subgroup analysis showed that Farxiga reduced the risk of the primary composite endpoint compared to placebo in patients with HFrEF without T2D.
This analysis evaluated the primary composite and its components and secondary endpoints in a subgroup of patients without T2D.
With Farxiga, the relative risk of the composite of worsening of HF or CV death was reduced by 27% among participants without diabetes (absolute risks 9.2% vs 12.7%, n=2605; HR 0.73 [95% CI 0.60, 0.88]) and by 25% in patients with diabetes (14.6% vs 19.4%, n=2139; HR 0.75 [95% CI 0.63, 0.90]).
All components contributed to the overall result. The data suggest that Farxiga has the potential to be a treatment for patients with HFrEF both with and without T2D.
Another pre-specified analysis presented, Effect of Treatment on the Kansas City Cardiomyopathy Questionnaire in the Dapagliflozin And Prevention of Adverse-outcomes In Heart Failure Trial (DAPA-HF), examined the effects of FARXIGA on HF related health status (symptoms, physical limitations and quality of life) in HFrEF, assessed using the KCCQ.
An improvement in the KCCQ total score for dapagliflozin compared to placebo was seen at 4 months, and the magnitude of the improvement was amplified at 8 months.
Furthermore, fewer patients treated with Farxiga had significant deterioration (≥5 points), and more experienced small (≥5 points), moderate (≥10 points) and large (≥15 points) clinically meaningful improvements in total KCCQ score.
The total symptom score on the KCCQ range from 0 to 100, with higher scores indicating fewer symptoms and physical limitations associated with HF and a change of 5 or more points considered to be clinically meaningful.
The Timing of Onset of Clinical Benefit with Dapagliflozin in Patients with Heart Failure: An Analysis from the Dapagliflozin And Prevention of Adverse-outcomes In Heart Failure Trial (DAPA-HF) post-hoc analysis explored the timing of onset of clinical benefit with Farxiga in patients with HFrEF compared to placebo. Reduction in the risk of the composite of worsening HF or CV death versus placebo was shown as soon as 4 weeks.
These exploratory data reinforce that Farxiga provided crucial early benefit for patients with HF.
The Effect of Treatment According to Age in the Dapagliflozin And Prevention Of Adverse-outcomes In Heart Failure Trial (DAPA-HF) subgroup analysis suggested that Farxiga may benefit outcomes in patients with HFrEF, regardless of age.
There was no apparent effect of age on the occurrence of adverse events or treatment discontinuation of dapagliflozin versus placebo.
The Influence of Ejection Fraction on the Effect of Treatment in the Dapagliflozin And Prevention Of Adverse-outcomes In Heart Failure Trial (DAPA-HF) subgroup analysis indicated that the treatment effects of dapagliflozin versus placebo were consistent over a broad spectrum of left ventricular ejection fraction (P interaction = 0.205 for primary composite outcome).
LVEF is a predictor of mortality and hospitalization related to HF.
These positive Farxiga results build on the DAPA-HF detailed results announced in September 2019. Farxiga is currently being studied in patients with HF with preserved ejection fraction (HFpEF) in the DELIVER and DETERMINE (HFrEF and HFpEF) trials.
Additionally, in September 2019, the US Food and Drug Administration granted Fast Track designation for Farxiga to reduce the risk of CV death, or the worsening of HF in adults with HFrEF or HFpEF based on the Phase III DAPA-HF and DELIVER trials.
The FDA also recently updated the Farxiga label to add an indication to reduce the risk of hospitalization for HF in adults with T2D and established CV disease or multiple CV risk factors. The approval was based on results from the landmark DECLARE-TIMI 58 CV outcomes trial, the largest SGLT2 inhibitors CVOT conducted to date.
DAPA-HF (Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure) is an international, multicenter, parallel group, randomized, double-blind trial in patients with heart failure and reduced ejection fraction (LVEF ≤ 40%), with and without T2D, designed to evaluate the effect of Farxiga 10mg, compared with placebo, given once daily in addition to standard of care.
The primary composite outcome was time to a worsening heart failure event (hospitalisation or equivalent event; i.e. an urgent heart failure visit), or cardiovascular death.
The full results of the DAPA-HF trial were published in The New England Journal of Medicine in September 2019.
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