medwireNews: A flurry of publications accompanying the primary findings of DELIVER shows dapagliflozin to benefit a wide range of people who have heart failure with preserved ejection fraction (HFpEF).
The primary findings showed a significantly reduced risk for worsening heart failure or cardiovascular death in people taking dapagliflozin versus placebo. The additional seven papers explore event-free survival as well as the effects of dapagliflozin according to age, frailty, BMI, recent hospitalization, N-terminal pro-B-type natriuretic peptide (NT-proBNP) level, and the presence of atrial fibrillation (AF).
The prespecified event-free survival analysis, published in the Journal of the American College of Cardiology, shows that people treated with dapagliflozin survived for approximately 2 years longer free of primary endpoint events than those taking placebo. The estimated additional event-free survival with dapagliflozin versus placebo was 2.0 at the age of 55 years, 2.3 years at age 65, and 1.2 years at age 75.
The analyses of frailty and age are published in Circulation and Circulation: Heart Failure, respectively. Frailty was assessed in 6258 of the 6263 DELIVER participants, showing that the frailest people (class 3 frailty, 23.8%) had the highest risk for primary endpoint events. Nevertheless, the risk in this group was reduced by a significant 26% with dapagliflozin versus placebo, which did not significantly differ from the 15% and 11% reductions achieved by participants with class 1 and class 2 frailty, respectively.
The researchers say their “findings should challenge any clinical reluctance to introduce dapagliflozin in patients perceived to be frail.”
Likewise, the “traditionally under-treated and most vulnerable older segment of patients,” ie, the 41% who were aged 75 years or older, had an 18% reduced risk for a primary outcome event with dapagliflozin versus placebo, which was in line with the 12–21% risk reduction seen in the younger age groups.
The BMI of the DELIVER participants, as reported in the European Heart Journal, ranged from 15.2 to 50 kg/m2, and obesity was common, affecting 44.6% of the cohort. There was a J-shaped relationship between BMI and primary outcome events, with the incidence lowest among overweight participants and highest in those with class 3 obesity. Once again, the benefit of taking dapagliflozin rather than placebo was consistent regardless of BMI.
Dapagliflozin was also beneficial for the 10.4% of participants who began treatment during hospitalization for heart failure or within 30 days after discharge. The analysis in JACC shows that dapagliflozin treatment resulted in a 22% reduction in risk for the primary outcome in this group, and an 18% reduction in the rest of the cohort.
Also in JACC, a publication focusing on AF reveals that dapagliflozin reduced the risk for the primary outcome by 22% in participants with the heart arrhythmia and 11% in those without, with no significant differences in the treatment effect according to AF status. People with AF had a higher risk for poor outcomes than those without overall, but not after accounting for confounders.
Finally, the DELIVER investigators found that baseline NT-proBNP levels had no influence on the clinical benefit participants gained from taking dapagliflozin, although there was an “especially large” absolute risk reduction in participants with high levels.
They explain in JACC: Heart Failure that previous research “raised concern that patients at the higher end of the natriuretic peptide spectrum might derive less benefit from therapies than those with lower natriuretic peptides.”
However, they note that “this may be specific to the biological pathways of the drugs in these trials.”
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