medwireNews: Dapagliflozin offers significant protection against worsening heart failure (HF) or cardiovascular death within 28 days of initiation, shows further analysis of DAPA-HF.
The trial included 4744 people who had HF with reduced ejection fraction (HFrEF), with or without type 2 diabetes.
After just 28 days of follow-up, participants randomly assigned to take dapagliflozin had a significant 49% reduction in the risk for the primary outcome of worsening HF (unplanned hospital admission or urgent visit requiring intravenous therapy) or cardiovascular death, compared with those taking placebo. By the end of the 2-year study, the risk reduction was 26%, but with a narrower confidence interval.
The benefit at 28 days was largely driven by a reduction in worsening HF events, for which there was a significant 52% reduction, whereas the reduction in cardiovascular death was a nonsignificant 13%.
David Berg (Brigham and Women’s Hospital, Boston, Massachusetts, USA) and co-researchers say their findings are consistent with the early protective effect reported for empagliflozin, and “underscore the opportunity for early clinical benefit when initiating dapagliflozin use in patients with chronic HFrEF.”
They add: “The rapid time to clinical benefit highlights the risk of delaying initiation of dapagliflozin in patients with HFrEF, a chronic, progressive disease with an insidious course that is often undertreated.”
Of note, the team found the protective effects of sodium-glucose cotransporter (SGLT)2 inhibition to be greatest in participants who had been hospitalized for HF within 12 months prior to study enrollment.
This applied to 27.4% of the cohort, and these people also had the highest overall risk during trial follow-up, with 33.8% meeting the primary endpoint. However, over the course of the whole trial, primary endpoint rates in this subgroup were 13.8 versus 21.6 per 100 patient–years for those taking dapagliflozin versus placebo. This equated to a 9.9% absolute risk reduction and a 36% relative reduction with the SGLT2 inhibitor.
A further 20.0% of participants had been hospitalized in the more distant past, 25.3% of whom met the primary endpoint. In this group, taking dapagliflozin rather than placebo resulted in a smaller but still significant 4.1% absolute risk reduction (27% relative reduction), while the 21.1% of participants who had never been hospitalized obtained a nonsignificant 2.1% absolute reduction (16% relative reduction).
“Consistent with prior studies, our analysis demonstrates that HF hospitalization is an important indicator of risk in patients with chronic HFrEF,” write the researchers in JAMA Cardiology.
And noting the emphasis in current guidelines on optimizing treatment to improve outcomes after HF hospitalization, they add that their findings “suggest that timing of prior HF hospitalization may identify patients who are likely to derive a greater absolute treatment benefit from SGLT2 inhibition.”
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