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Details of DAPA-HF Results Point to Dapagliflozin for Some Heart Failure Patients Without Diabetes

Mary Caffrey
Patients without diabetes who have heart failure saw signficant benefits from the sodium glucose cotransporter 2 inhibitor dapagliflozin, prompting a commenter to ask not if more patients should be taking these drugs but when to start patients on them. 
The sodium glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin, developed for patients with type 2 diabetes (T2D), keeps certain heart failure (HF) patients out of the hospital whether or not they have diabetes, according to experts appearing Saturday at the 2019 American Heart Association (AHA) Scientific Sessions in Philadelphia.

Adding the SGLT2 inhibitor can bring benefits for HF patients with reduced ejection fraction (HFrEF) even if they are already on intense therapy, according to details of the DAPA-HF trial presented in a late-breaking session at AHA. Dapagliflozin is sold as Farxiga by AstraZeneca.

Larry Allen, MD, MHS, a HF specialist from the University of Colorado, who offered commentary on the results, said during the session that question now isn’t whether HF patients should be taking dapagliflozin. “The real question is when to add these drugs,” Allen said, since less than 5% of patients with HFrEF are taking an SGLT2 inhibitor.

“We need to do a better job of aligning incentives,” Allen said, which will require avoiding the high out-of-pocket costs that keep patients from taking therapies that will keep them out of the hospital. Medicare has pushed health systems to reduce hospitalization for HF, and commercial plans have followed suit; the CDC estimates that the total cost of this condition is more than $30.7 billion per year in the United States.

DAPA-HF, first unveiled in September at the European Society of Cardiology in Paris, answered a question that many had wondered about for some time: Would the reduction in cardiovascular (CV) death and hospitalization for HF, which turned up in FDA-mandated CV outcomes trials for SGLT2 inhibitors, also be seen when this class was studied in patients without diabetes?

The answer in Paris was a resounding yes. Patients with and without diabetes who had HFrEF showed the reduction of 26% for the combined end point of CV death and worsening of HF, alongside standard of care. Worsening of HF included both hospitalizations and urgent HF visits.

At AHA on Saturday, lead investigator John McMurray, MD, of the University of Glasgow, Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, shed additional light on the DAPA-HF results: benefits for those without diabetes showed up soon after patients began taking dapagliflozin and were consistent, regardless of patients’ baseline level of glycated hemoglobin (A1C).

Those with T2D had a 21% reduction in CV death, while the reduction was 15% in patients without diabetes. The relative benefit was reversed in worsening of HF: Among patients with T2D, there was a 23% reduction in events, while there was a 38% reduction in HF events among those without diabetes.

DAPA-HF included 2139 patients with T2D (45%) and 2605 without diabetes. A small number, 165 patients, had previously undiagnosed T2D. Both groups had similar HF profile, with at least New York Heart Association Class II; 49% of the T2D group had prior HF hospitalization, compared with 46% of the group without diabetes.

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