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HF Benefit of Dapagliflozin Affirmed in Non-Diabetics

<ѻý class="mpt-content-deck">— Fewer CV events for heart failure with reduced ejection fraction
MedpageToday

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PHILADELPHIA -- Heart failure patients with reduced ejection fraction but no diabetes appear to benefit significantly when the diabetes drug dapagliflozin (Farxiga) is added to their treatment regimens, researchers reported here.

The composite primary endpoint of cardiovascular death, heart failure hospitalization, and urgent heart failure visits over an average 18.2 months was reduced by 27% among people not diagnosed with diabetes who were randomized to dapagliflozin 10 mg once daily compared with placebo (HR 0.73, 95% CI 0.60-0.88), reported John McMurray, MD, of the British Heart Foundation Cardiovascular Research Centre at the University of Glasgow, Scotland.

As for diabetics in the DAPA-HF trial, there was a 25% reduction in primary endpoint events comparing the sodium glucose co-transporter-2 (SGLT-2) inhibitor against placebo (HR 0.75, 95% CI 0.63-0.90), McMurray noted during his late-breaker presentation at the annual scientific sessions of the .

Main findings from DAPA-HF were first presented at the European Society of Cardiology meeting in September. The present subgroup analysis stratifies outcomes by diabetes status.

"Exactly why dapagliflozin works in non-diabetic patients is not really known but may be related to its effect on kidney function. It has a number of effects not only in the kidney but also in the body in terms of neurohormonal antagonism. So it is not surprising to think that we could have effect beyond diabetes," Larry Allen, MD, of the University of Colorado Anschutz Medical Campus in Aurora, told ѻý.

Allen, the AHA discussant for DAPA-HF, said the evidence of the benefit of SGLT-2 inhibitors in other clinical trials had led him to use the drugs in his patients. "So what you are seeing around the community now is that if I have a patient that has diabetes and heart failure, many of us are starting to use these agents in those patients with diabetes. Where we are going next is: are those drugs going to be approved and largely paid for in these patients who don't have diabetes?"

"DAPA-HF suggests there is strong reason to consider that and for payors to think about paying for it. To prescribe these drugs in non-diabetics now requires pre-authorization. I don't think the payors have caught up with the data," Allen commented.

In the DAPA-HF trial, McMurray and colleagues enrolled 4,744 patients with heart failure characterized by reduced ejection fraction (left ventricular ejection fraction of 40% or less) from 20 countries. Overall, patients were about 67 years old and more than 75% were men; the vast majority of the patients were diagnosed in New York Heart Association heart failure class II or III. Their mean left ventricular ejection fraction was 31%.

There were 2,139 patients diagnosed with diabetes included in the trial. This subgroup was more likely to have a heart failure etiology of ischemia compared to non-diabetics (61% vs 51%).

Patients diagnosed with diabetes achieved a 23% reduction in the composite of death and heart failure hospitalizations on dapagliflozin (HR 0.77, 95%CI 0.63-0.94), while there was a 27% reduction among those who did not have diabetes (HR 0.73, 95% CI 0.59-0.91), McMurray noted.

"The relative and absolute risk reductions in death and hospitalization were substantial, clinically important and consistent in patients with and without type 2 diabetes," he said.

He also showed that when patients without diabetes were stratified by HbA1c levels, there was a consistent reduction between 26% to 29% in adverse events when compared with placebo.

McMurray said dapagliflozin was well tolerated by patients with and without diabetes when compared with patients who were treated with placebo.

"Dapagliflozin offers a new approach to the treatment of heart failure with reduced ejection fraction in patients with and without type 2 diabetes," he concluded.

Disclosures

The study was funded by AstraZeneca

McMurray disclosed no relevant relationships with industry. Co-authors disclosed relevant relationships with most companies involved in cardiovascular research, including AstraZeneca.

Allen disclosed no relevant relationships with industry regarding SGLT2 agents, but said he has relationships with industry in other areas of research.

Primary Source

American Heart Association Scientific Sessions

McMurray J et al "The dapagliflozin and prevention of adverse-outcomes in heart failure Trial (DAPA-HF): Results in nondiabetic patients" AHA 2019.