Dapagliflozin Linked with Reduced Morbidity, Mortality in HFrEF Patients Irrespective of Diabetes

Dapagliflozin reduced cardiovascular morbidity and mortality in patients with heart failure with reduced ejection fraction (HErEF) regardless of diabetes status, a new study suggests.

“Additional treatments are needed for heart failure with reduced ejection fraction (HFrEF),” the authors, publishing in Journal of the American Medical Association (JAMA), wrote in their study. “Sodium-glucose cotransporter 2 (SGLT2) inhibitors may be an effective treatment for patients with HFrEF, even those without diabetes.”

To evaluate the effects of dapagliflozin in patients with heart failure with reduced ejection fraction both with and without diabetes, the exploratory analysis included patients with NYHA class II to IV with ejection fraction rates less than or equal to 40% and elevated plasma NT-proBNP. Patients (n=4,744) were given a once-daily dose of 10 mg dapagliflozin (or placebo) added to regular therapy. The primary study outcome was composite worsening heart failure or cardiovascular death, and outcomes were analyzed by diabetes status.

Now out in @JAMA_current: https://t.co/uF5bXpdrne

Dapagliflozin in HFrEF w/o DM n=2605 [55%] in #DAPAHF

✅Comparable relative & absolute benefits
✅Neither major hypoglycemia nor DKA in *any* pt
✅Low rates of volume depletion
✅Strikingly, very limited glycemic potential 👇 pic.twitter.com/FdLayKVRQr

— Muthu Vaduganathan (@mvaduganathan) March 28, 2020

According to the results, 4,742 patients completed the trial. Among patients without diabetes, the primary study outcome occurred in 13.2% of patients in the dapagliflozin group and 17.7% in the placebo group (HR=0.73; 95% CI, 0.60 to 0.88). In diabetic patients, the primary study outcome occurred in 20.0% in the dapagliflozin group and 25.5% in the placebo group (HR=0.75; 95% CI, 0.63 to 0.90; P for interaction=0.80). In patients without diabetes and with a glycatred hemoglobin of at least 5.7%, the primary outcome occured in 13.7% of those in the dapagloflozin group and 18.0% in the placebo group (HR=0.74; 95% CI, 0.59 to 0.94; P for interaction=0.72).

“In this exploratory analysis of a randomized trial of patients with HFrEF, dapagliflozin compared with placebo, when added to recommended therapy, significantly reduced the risk of worsening heart failure or cardiovascular death independently of diabetes status,” the researcher wrote in their conclusion.

#Dapagliflozin was effective at reducing cardiovascular morbidity and mortality in patients with #heartfailure and reduced ejection fraction independent of #diabetes status https://t.co/RqLhkr15J3 #VisualAbstract

— JAMA (@JAMA_current) March 27, 2020

Some excellent non #COVID19 reading on dapagliflozin in heart failure following on from DAPA-HF from Dr Kieran Docherty! 🧪 💔➡️❤️ https://t.co/lTcMHcbv6g

— Anna Kate Barton (@AnnaKateBarton) March 27, 2020

Remarkable. This isn't a diabetes drug that improves CV outcomes. This is a CV drug that benefits glycemic homeostasis https://t.co/CEzzNzP1P7

— Charles Pollack MD (@md_pollack) March 28, 2020