In HF, dapagliflozin benefits similar in patients with improved vs. consistently high EF
NATIONAL HARBOR, Md. — In a DELIVER subgroup analysis, dapagliflozin conferred similar benefit in patients with HF with improved ejection fraction prior to trial enrollment compared with those with consistently high EF.
“Heart failure with improved ejection fraction ... has been recently defined as heart failure with previously reduced left ventricular ejection fraction of 40% or less, and a subsequent measurement of EF that increases to greater than 40%,” Orly Vardeny, PharmD, MS, associate professor of medicine at the University of Minnesota, said during a presentation at the Heart Failure Society of America Annual Scientific Meeting. “Advances in the treatment of HFrEF with [guideline-directed medical therapy] have resulted in a rapid growth of the pool of patients with improved EF. Recent U.S.-based guidelines recommend that patients with improved EF continue treatment with [guideline-directed medical therapy] to avoid relapse and worsening of left ventricular function. Previous therapeutic heart failure outcomes trials have excluded individuals with improved EF. Whether initiation of specific new pharmacologic therapies might improve clinical outcomes in these patients is unknown.”
For the DELIVER trial, researchers randomly assigned 6,263 patients with HF and LVEF more than 40%, with or without type 2 diabetes, to receive once-daily dapagliflozin (Farxiga, AstraZeneca) 10 mg or placebo, in addition to usual therapy, for a median of 2.3 years (71% white; 44% women). The primary outcome was a composite of worsening HF, defined as unplanned HF hospitalization or urgent HF visit, or CV death.
As Healio previously reported, dapagliflozin in adults with HF with mildly reduced or preserved EF was associated with lower risk for CV death and worsening HF; no attenuation of treatment benefit for patients with the highest EF; fewer total HF hospitalizations; and a marked improvement in symptom burden compared with placebo.
Vardeny said patients with prior LVEF of 40% or less were permitted to participate in DELIVER so long as their EF at study baseline was more than 40%. Therefore, this subgroup analysis aimed to evaluate the effects of dapagliflozin among patients with HF and improved EF, with and without diabetes.
Patients with HF with improved EF had elevated risk for disease progression of a similar magnitude to those with EF consistently more than 40%, Vardeny said during the presentation.
Researchers observed no significant difference in risk for the primary composite outcomes (P for interaction = .426) or any of the secondary endpoints, including CV death (P for interaction = .086), HF events (P for interaction = .687), HF hospitalization (P for interaction = .991), all-cause death and a composite of CV death (P for interaction = .628) and recurrent HF events (P for interaction = .334) in patients in HF with improved EF compared with those with EF consistently more than 40%.
There was also no significant difference in risk for the primary composite endpoint when patients with improved EF were compared with those with EF of 49% or less, 50% to 59% or at least 60% (P = .27).
“Despite previous improvement in EF, patients with heart failure with improved ejection fraction in DELIVER encounter heightened risk of disease progression, including worsening heart failure events or death, which were comparable to those that had an EF consistently over 40%,” Vardeny said during the presentation. “In patients enrolled in the DELIVER study who had heart failure with improved ejection fraction, dapagliflozin compared with placebo reduced the composite of cardiovascular death or worsening heart failure to a similar extent as patients with EF consistently over 40%. These data are the largest randomized findings in this population and suggest that patients with heart failure with improved ejection fraction and remain symptomatic may benefit from the addition of an SGLT2 inhibitor to previously instituted GDMT to further reduce morbidity or mortality.”
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The DELIVER analysis looked at the group of patients with improved EF in HF and showed benefits of dapagliflozin comparable to patients who had continuously high EF. It’s a group that has not really been studied extensively, and so that’s what the most important contribution is. Many patients who have an improved EF will have resolution symptoms, though. I don’t think you want to group those patients with the patients who have persistent HF, even though their EF improved. But it’s an important step forward just to look at a population that has not yet been well studied.
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Vardeny O, et al. Late Breaking Clinical Trials Session I. Presented at: The Heart Failure Society of America Annual Scientific Meeting; Sept. 30-Oct. 3, 2022; National Harbor, Maryland (hybrid meeting).
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