medwireNews: People who have heart failure with preserved ejection fraction (HFpEF) benefit from dapagliflozin irrespective of whether they have normal or impaired glucose metabolism, shows further analysis of DELIVER.
However, the researchers stress that the absolute risk for a primary outcome event (worsening heart failure event or cardiovascular death) was higher with increasing baseline glycated hemoglobin (HbA1c) level, meaning that “the absolute risk reduction with dapagliflozin tended to be most favourable” for people with type 2 diabetes.
Based on HbA1c levels, 18.8% of the 6263 DELIVER participants had normoglycemia, 30.9% had prediabetes, and 50.3% had type 2 diabetes. The incidence rates of the primary outcome in these subgroups were a corresponding 6.9, 7.6, and 10.1 per 100 patient–years.
However, people benefited from dapagliflozin treatment regardless of their baseline HbA1c. The primary outcome rates per 100 patient–years were 6.0 versus 7.8 for people with normoglycemia taking dapagliflozin and placebo, respectively, 7.1 versus 8.2 for those with prediabetes, and 9.0 versus 11.2 for those with type 2 diabetes.
The numbers needed to treat were 56, 91, and 46 in the normoglycemia, prediabetes, and type 2 diabetes subgroups, respectively.
Likewise, when Silvio Inzucchi (Yale School of Medicine, New Haven, Connecticut, USA) and co-researchers considered HbA1c as a continuous variable, they found that people benefitted from dapagliflozin versus placebo irrespective of their glucose levels.
“These results extend the efficacy of dapagliflozin in patients with heart failure with reduced ejection fraction from DAPA-HF to those with heart failure and mildly reduced ejection fraction or preserved ejection fraction,” the team writes in The Lancet Diabetes & Endocrinology.
In a linked commentary, Hertzel Gerstein (McMaster University and Hamilton Health Sciences, Ontario, Canada) and Naveed Sattar (University of Glasgow, UK) say the study supports the heart failure benefits of sodium-glucose cotransporter 2 inhibitors being independent of their glucose-lowering effects.
They also highlight the high prevalence of dysglycemia among people with HFpEF and the particularly large absolute benefit of dapagliflozin in people with type 2 diabetes.
But the commentators stress that “despite its heart failure benefits, dapagliflozin does not eliminate the excess risk of heart failure associated with dysglycaemia, a finding that strongly supports ongoing research into cardioprotective therapies for people with dysglycaemia.”
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Lancet Diabetes Endocrinol 2022; doi:10.1016/S2213-8587(22)00308-4
Lancet Diabetes Endocrinol 2022; doi:10.1016/S2213-8587(22)00313-8