DEFINE-HF: Further support for add-on dapagliflozin as a treatment option for heart failure
medwireNews: Results of the DEFINE-HF trial indicate that add-on dapagliflozin treatment may improve health status among people with established heart failure and reduced ejection fraction (HFrEF).
However, 12 weeks of treatment with the sodium-glucose cotransporter (SGLT)2 inhibitor in addition to guideline-directed therapy had no significant impact on the co-primary endpoint of average N-terminal pro b-type natriuretic peptide (NT-proBNP) levels, report Mikhail Kosiborod (Saint Luke’s Mid America Heart Institute, Kansas City, Missouri, USA) and colleagues.
The DEFINE-HF (Dapagliflozin Effects on Biomarkers, Symptoms, and Functional Status in Patients With Heart Failure with Reduced Ejection Fraction) trial included 263 HF patients with left ventricular ejection fraction of 40% or less, 62% of whom also had type 2 diabetes. All participants had New York Heart Association class II–III symptoms, and 85% had previously been hospitalized for HF.
Kosiborod and team found that the 131 patients who were randomly assigned to receive oral dapagliflozin 10 mg/day were significantly more likely than the 132 participants given placebo to achieve a clinically meaningful improvement in HF-specific health status – indicated by at least a 5-point increase in the average of the 6- and 12-week Kansas City Cardiomyopathy Questionnaire overall summary scores – or a meaningful reduction in NT-proBNP levels (≥20% decrease in average of 6- and 12-week levels).
A total of 61.5% and 50.4% of patients in the dapagliflozin and placebo groups, respectively, met this endpoint, translating into a significant odds ratio (OR) of 1.8 after adjustment for potentially confounding factors.
Therefore, “dapagliflozin may have a favorable effect on improving disease-specific health status (symptoms, function and quality of life) in patients with HFrEF,” say the investigators, noting that results were consistent in participants with and without type 2 diabetes.
Average 6- and 12-week adjusted NT-proBNP levels were comparable in the dapagliflozin and placebo groups, however, at 1133 pg/dL and 1191 pg/dL, respectively.
Kosiborod et al suggest that a number of reasons could explain why dapagliflozin improved one primary outcome but not the other, including variability of NT-proBNP levels at baseline (standard deviation of around 2300 pg/mL), which may have “precluded the detection of anything less than a very large change.”
They report that dapagliflozin had “a reassuring safety profile” in the trial, with no imbalance in rates of adverse events between the groups.
The investigators emphasize that the DEFINE-HF results “were achieved in the context of high rates of background guideline-directed optimal medical therapy for HFrEF,” with more than 95% of patients receiving beta blockers, more than 60% taking mineralocorticoid antagonists, and 59% on angiotensin converting enzyme inhibitors or angiotensin receptor blockers.
While the DAPA-HF trial demonstrated a beneficial effect of dapagliflozin on hard outcomes, and other large HF outcomes trials are presently underway, the researchers note that DEFINE-HF “is the first randomized controlled trial to explore the effects of an SGLT-2 [inhibitor] on natriuretic peptides and health status.”
The DEFINE-HF results are published in Circulation, and were presented at the Heart Failure Society of America 23rd Annual Scientific Meeting in in Philadelphia, Pennsylvania, USA.
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