The FDA has awarded a further implication for dapagliflozin (Farxiga, AstraZeneca Pharmaceuticals), heart failure medication, the first sodium-glucose co-transporter 2 (SGLT2) inhibitor to be allowed to decrease the chance for cardiovascular (CV) death and hospitalization in adults with heart failure (HF; NYHA class II-IV) with reduced ejection fraction (HFrEF) with and without type 2 diabetes.
The support was based on events from the landmark phase 3 DAPA-HF trial, written in The New England Journal of Medicine (2019;381:1995-2008). The research has shown that dapagliflozin produced a statistically important and clinically significant decrease in CV death or hospitalization for HF, associated with placebo.
An In-Depth Review
The decision reflects the advantage review classification granted by the FDA first this year and the fast track appointment awarded in September 2019, according to an AstraZeneca press statement announcing the endorsement.
“Heart failure is a severe health state that offers to one in eight deaths in the U.S. and affects nearly 6.5 million Americans,” stated Norman Stockbridge, MD, Ph.D., the manager of the Division of Cardiology and Nephrology in the FDA’s Center for Drug Evaluation and Research.
“This support gives sufferers with decreased dismissal fraction an supplementary therapy option that can increase endurance and decrease the requirement for hospitalization.”
Heart Failure Medication Effectiveness
The DAPA-HF trial involved 4,744 members. Their average age was 66 years, and more members were male (77%) than females. To define the drug’s effectiveness, researchers studied the survival of CV death, hospitalization for HF, and critical HF visits.
Shareholders were randomly selected to receive a dose of 10 mg of dapagliflozin or a placebo, once daily.
The research showed that dapagliflozin, in addition to example of care, decreased the risk for the composite outcome of CV death or worsening of HF versus placebo by 26% (absolute risk loss, 5% [event rate/100 patient-years, 11.6 vs. 15.6, only]; P<0.0001) in sufferers with HFrEF.
Decrease In Heart Diseases
During the trial, one CV death or hospitalization for HF or an urgent visit compared with HF could be withdrawn for every 21 patients operated with dapagliflozin, according to AstraZeneca.
The safety profile of dapagliflozin in the DAPA-HF trial “was compatible with the well-established security profile of the drug,” the company noted.
“The ground-breaking issues of the DAPA-HF trial have converted heart failure therapeutics,” John McMurray, MD, of the Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, U.K., told in the AstraZeneca press statement.
“Current support presents practitioners with a totally novel pharmacological strategy that greatly improves outcomes for patients with heart failure with reduced ejection fraction.”
A Meaningful Influence
Mene Pangalos, AstraZeneca executive vice president of BioPharmaceuticals R&D, added:
“With the endorsement of Farxiga, we have entered a significant milestone to possibly transform heart failure therapy for the millions of people living with the disease in the U.S. We are now one step closer to making a meaningful influence on their lives by providing much-needed therapy to assist reduce their disease burden and live longer.”
Dapagliflozin can produce dehydration, stubborn urinary tract infections, and genital yeast diseases. Elderly sufferers, patients with kidney diseases, those with hypotension, and sufferers on diuretics should be charged for their volume status and kidney function.
Sufferers with signs and symptoms of metabolic acidosis or ketoacidosis also should be assessed. Dapagliflozin can cause difficult cases of necrotizing fasciitis of the perineum (Fournier’s gangrene) in people with diabetes and hypoglycemia when mixed with insulin.