DAPA-HF: Dapagliflozin Scores a Win in Heart Failure
Topline results show the primary endpoint was met in this phase III trial, which included patients with and without diabetes.
Dapagliflozin (Farxiga), originally developed for the treatment of type 2 diabetes, has become the first drug in its class to show a significant clinical benefit in a phase III trial of patients with chronic heart failure with reduced ejection fraction who were not required to have diabetes, drugmaker AstraZeneca announced Tuesday.
Given on top of standard heart failure therapies, the sodium glucose co-transporter 2 (SGLT2) inhibitor reduced the primary composite endpoint of worsening heart failure or cardiovascular death versus placebo in the 4,744-patient DAPA-HF trial. The study included patients both with and without diabetes, according to a press release from the company. The full results will be presented at the upcoming European Society of Cardiology Congress in Paris, France.
“The safety profile of Farxiga in the DAPA-HF trial was consistent with the well-established safety profile of the medicine,” the company reported. The drug’s label lists the most common adverse reactions as female genital mycotic infections, nasopharyngitis, and urinary tract infections.
The announcement marks the latest serendipitous twist in the tale for diabetes drugs, coming more than a decade after the US Food and Drug Administration first mandated cardiovascular outcomes trials for up-and-coming diabetes medications. Over the last few years, trials of the SGLT2 inhibitors have delivered positive results in such trials in diabetic patients. In DECLARE-TIMI 58, for example, dapagliflozin reduced the composite of cardiovascular death or hospitalizations for heart failure (driven by the latter component) in patients with type 2 diabetes and high cardiovascular risk. The other two SGLT2 inhibitors have been shown to reduce heart failure hospitalizations in high-risk patients with type 2 diabetes as well.
Manufacturers have since turned to the question of whether these agents might also prove useful in patients with established heart failure, including individuals with normal glucose levels. The topline DAPA-HF results are the first glimpse at the data in this space although, of note, this preliminary announcement does not include information on outcomes stratified by presence or absence of diabetes.
All of the approved SGLT2 inhibitors are indicated as adjuncts to diet and exercise to improve glycemic control in adults with type 2 diabetes, and none of them have a heart failure-related indication. However, empagliflozin has gained an indication for reducing the risk of cardiovascular death in adults with type 2 diabetes and established cardiovascular disease and canagliflozin has earned an indication for reducing MACE in the same types of patients.
AstraZeneca is continuing to study the potential for dapagliflozin to improve outcomes in patients with heart failure in multiple trials. Aside from DAPA-HF, DELIVER is testing the effect of the drug on cardiovascular outcomes in patients with heart failure with preserved ejection fraction and DETERMINE is evaluating the effects on exercise capacity in patients with either preserved or reduced ejection fraction.