Cardioprotective benefits of dapagliflozin extend beyond people with diabetes
medwireNews: Treatment with dapagliflozin is associated with a significant reduction in the risk for heart failure worsening or cardiovascular death in people with heart failure and reduced ejection fraction (HFrEF) regardless of whether or not they have diabetes, shows an exploratory analysis of DAPA-HF trial data.
John McMurray (University of Glasgow, UK) and co-investigators say their data “provide evidence that the benefits of SGLT2 [sodium-glucose cotransporter 2] inhibition are not limited to people with diabetes or prediabetes and are applicable to patients with heart failure with reduced ejection fraction, irrespective of glycemic status.”
The DAPA-HF trial, reported previously by medwireNews, included 4744 patients (mean age 66 years, 23% women) from 20 countries who had a New York Heart Association classification of II–IV, an ejection fraction at or below 40%, and elevated plasma N-terminal pro B-type natriuretic peptide.
Participants were randomly assigned to receive dapagliflozin 10 mg once daily (n=2373) or placebo (n=2371), both given alongside their recommended therapy. In each group, 45% of participants had type 2 diabetes.
After a median 18 months of follow-up, the risk for the primary composite outcome of heart failure worsening (unplanned hospital admission or treatment with intravenous therapy) or cardiovascular death among the patients with diabetes was a significant 25% lower among those receiving dapagliflozin than among those receiving placebo, with rates of 20.0% and 25.5%, respectively.
For the participants without diabetes, the risk for this outcome was a significant 27% lower with versus without dapagliflozin, at rates of 13.2% and 17.7%, respectively, and there was no significant difference in treatment effect according to diabetes status.
A similar pattern was observed among the people without diabetes who were stratified according to baseline glycated hemoglobin (Hb1Ac) level. Those with an HbA1c below 5.7% (39 mmol/mol) had a significant 33% lower risk for heart failure worsening or cardiovascular death if they received dapagliflozin, while people with an HbA1c of 5.7% or higher (ie, prediabetes) had a 26% lower risk, relative to placebo.
The researchers also found that dapagliflozin had similar beneficial effects on weight, blood pressure, estimated glomerular filtration rate, and N-terminal pro B-type natriuretic peptide, in the patients with and without diabetes, but only lowered HbA1c in those with diabetes.
“These findings suggest the benefits of dapagliflozin were independent of plasma glucose lowering,” McMurray and co-authors remark in JAMA.
In an accompanying comment, Bruce Neal and Clare Arnott, both from the University of New South Wales Sydney in Australia, said this “highly informative exploratory analysis of the most recent large-scale clinical trial of an SGLT2 inhibitor […] may suggest the next chapter for this drug class—the transition from a glucose-lowering therapy that provides cardioprotection to a cardioprotective agent that happens to lower blood glucose.”
They add: “Widespread application of the results of the DAPA-HF trial should directly improve clinical outcomes for patients with heart failure, but the observation of benefit for the patients without diabetes may have the most far-reaching implications.”
And the commentators conclude: “A large new body of research is now required to define the full potential of this class for patients without diabetes.”
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