First detailed results from landmark Phase III DAPA-HF trial published
Forxiga (dapagliflozin) 10mg, on top of standard of care, reduced the incidence of cardiovascular death or the worsening of heart failure, according the first detailed results from the landmark Phase III DAPA-HF trial.
DAPA-HF is the first outcomes trial with an SGLT2 inhibitor investigating the treatment of heart failure in patients with reduced ejection fraction (HFrEF) with and without type 2 diabetes, AstraZeneca has announced. The detailed results were presented on September 1 at the ESC Congress 2019 in Paris, France.
Dapagliflozin is not licensed for the treatment of heart failure.
Dapagliflozin was as effective in heart failure patients without diabetes as in those with diabetes. Professor John McMurray
The data presented yesterday showed that, for the primary composite endpoint, dapagliflozin 10mg reduced the risk of cardiovascular (CV) death or worsening of heart failure by 26% (Hazard Ratio [HR] 0.74 [0.65,0.85]; Absolute Risk Reduction [ARR]=4% [event rate/100 patient years: 11.6 vs 15.6]; p=0.00001) and showed a reduction in each of the individual components of the composite endpoint, compared to placebo. Worsening of heart failure was defined as unplanned hospitalisation for heart failure or an urgent heart failure visit requiring intravenous therapy.
John McMurray, MD, University of Glasgow, Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, said: “We are very pleased that dapagliflozin was so effective in our trial – it did all the things we would like any drug to do in heart failure which are to improve symptoms, reduce hospital admissions and increase survival. Even better, dapagliflozin was as effective in heart failure patients without diabetes as in those with diabetes.”
Over half a million people in the UK are living with heart failure, a life-threatening disease in which the heart cannot pump blood effectively around the body. It is a long-term condition that is often degenerative and where over half of patients will die within five years of diagnosis. It is the leading cause of hospitalisation for those over the age of 65 and represents a significant clinical and economic burden, accounting for 2% of all NHS inpatient bed days.
Laurent Abuaf, Country President, AstraZeneca UK, said: “Heart failure places an immense burden on patients and their families, and results in around one million inpatient bed days in England and Wales every year. Dapagliflozin has been used for several years in the treatment of type 2 diabetes and it is exciting to see the potential of this medicine for patients with heart failure.”
The components of the primary composite endpoint were also analysed separately. Compared to placebo, there was a 30% relative risk reduction (HR 0.70 [0.59, 0.83]; ARR=3% [event rate/100 patient years: 7.1 vs 10.1]; p=0.00003) of worsening heart failure and an 18% relative risk reduction (HR 0.82 [0.69, 0.98]; ARR=1.4% [event rate/100 patient years: 6.5 vs 7.9]; p=0.029) of CV death when patients were treated with dapagliflozin on top of standard of care. The effect of dapagliflozin on the primary composite endpoint was generally consistent across the key subgroups examined.
In addition, there was a significant improvement in patient reported outcomes measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ) total symptom score (+6.1 vs +3.3 for dapagliflozin and placebo respectively; [1.6, 4.0] p<0.001). Other secondary endpoints were also examined.
The safety profile of dapagliflozin in the DAPA-HF trial was consistent with the known safety profile of the medicine. The proportion of patients with volume depletion (7.5% versus 6.8%) and renal adverse events (6.5% vs 7.2%), which are commonly of concern when treating heart failure, were comparable to placebo. Major hypoglycaemic events were 0.2% in both treatment groups.