Dapagliflozin Cuts Risk of CV Death, Worsening of Heart Failure 26%, Whether Diabetes Present or Not

Dapagliflozin, sold by AstraZeneca as Farxiga, cuts the risk of cardiovascular (CV) death and worsening of heart failure (HF) by 26% among patients with reduced ejection fraction alongside standard of care, according to results of a landmark phase 3 study presented September 1, 2019, at the European Society of Cardiology 2019 Congress in Paris, France.

Full results from DAPA-HF confirmed that the sodium glucose co-transporter 2 (SGLT2) inhibitor, already approved to treat type 2 diabetes (T2D), is just as effective in preventing CV death and HF events in patients who do not have T2D.

Topline results announced last month noted that the trial's end point had been met, but today’s presentation was the first time data were shared showing that the drug worked equally well in patients who had HF but not diabetes. This possibility has been the topic of much speculation since cardiovascular outcomes trials in the SGLT2 inhibitor class showed the drugs’ ability to reduce hospitalization for HF, although only the DECLARE-TIMI study on dapagliflozin included this as a primary end point.

The finding that patients with reduced ejection fraction (HFrEF) had a 30% reduced risk of a first episode of HF—such as a hospitalization or trip to the emergency department—is certain to draw the attention of health systems, which have been under pressure from CMS and other payers to reduce 30-day readmissions for HF. According to the CDC, about 5.7 million people in the United States have HF, and the condition costs $30.7 billion each year in medical services, therapies, and lost days from work.

Also of interest to health systems: results for subgroups that show dapagliflozin was especially effective for patients who are obese—they saw a 31% reduced risk—and those who have at least 1 hospitalization for HF; this group saw a 33% reduced risk in the combined end point.

Separately, the results found that patients taking the therapy reduced their risk of CV death by 18%.

Lead study author John McMurray, MD, University of Glasgow, Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, said in a statement: “We are very pleased that Farxiga 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, Farxiga was as effective in heart failure patients without diabetes as in those with diabetes.”

DAPA-HF randomized 4744 patients, with a mean age of 66 for the study drug and 67 for placebo; 76% of those taking the study drug were men, while 77% of the placebo group were men. At baseline, 42% of the group had previously been diagnosed with T2D, and 45% turned out to have T2D when the study began (percentages were the same in the dapagliflozin and plabeco arms).

Patients were taking a variety of other standard therapies, including diuretics, angiotensin-converting-enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), or angiotensin receptor neprilysin inhibitors (ARNI), beta blockers, and mineralocorticoid receptor antagonists (MRAs).

According to McMurray’s presentation, findings showed:

• For the primary composite outcome of CV death, HF hospitalization or an urgent HF visit the hazard ratio (HR) was 0.74 (0.65-0.85, P = .00001.)
• Within the components of the primary outcome, for a worsening HF event, the HR was 0.70 (0.59-0.83, P = .00003). For CV death, the HR was 0.82 (0.69-0.98, P =. 029).
• Benefits for those with or without T2D were nearly identical. For T2D, the HR was 0.75 (0.63-0.90); for those without, HR 0.73 (0.60-0.88).
• For those with prior hospitalization for HF, the benefit was substantial: HR was 0.67 (0.56-0.80); among those without a prior hospitalization, HR was 0.84 (0.69-1.01).
• Benefits increased for those who were obese, which is defined by CDC as having a body mass index (BMI) of 30 kg/m² or higher. Among those with a BMI below 30, the HR was 0.78 (0.66-0.92); for those with BMI of at least 30, the HR was 0.69 (0.55-0.86).

According to a statement from AstraZeneca, the results also showed a significant improvement in patient-reported outcomes, based on measures of the Kansas City Cardiomyopathy Questionnaire (KCCQ) total symptom score, as well as a 17% reduction in all-cause mortality for patients taking dapagliflozin.

Safety results were consistent with prior studies. Dapagliflozin in HF is the subject of 2 other trials: DELIVER is examining the drug in patients with preserved ejection fraction (HFpEF), while DETERMINE is studying patients with both HFrEF and HFpEF. Competing makers of SGLT2 inhibitors are also studying the drugs’ effectiveness in HF.

AstraZeneca funded DAPA-HF.