DELIVER: Dapagliflozin cuts risk for worsening HF in adults with, without type 2 diabetes
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Dapagliflozin reduces risk for worsening heart failure and cardiovascular death in adults with heart failure with mildly reduced or preserved ejection fraction, regardless of baseline HbA1c, according to findings from the DELIVER trial.
As Healio previously reported, in the DELIVER trial, adults with heart failure (HF) with mildly reduced and preserved ejection fraction were randomly assigned 10 mg dapagliflozin (Farxiga, AstraZeneca) or placebo daily for a median of 2.3 years. In the overall analysis, participants receiving dapagliflozin had a lower risk for the primary outcome of worsening HF or CV death compared with placebo. In new data presented at the European Association for the Study of Diabetes annual meeting, researchers analyzed DELIVER trial findings by diabetes status, with participants divided into groups without diabetes, with prediabetes or with type 2 diabetes.
“We found no statistical interaction between the categorical glycemic subgroupings nor using HbA1c as a continuous variable and dapagliflozin treatment benefit,” Silvio E. Inzucchi, MD, professor of medicine at Yale University School of Medicine and Yale-New Haven Hospital, said during the presentation. “There were also no significant trends based on diabetes duration, baseline HbA1c, metformin or insulin therapy at baseline.”
Risk for adverse HF outcomes higher with diabetes
Researchers enrolled adults aged 40 years or older with HF and left ventricular ejection fraction of more than 40% to participate in DELIVER. The trial’s primary endpoint was time to worsening HF, defined as a HF hospitalization or urgent HF visit, or CV death.
Researchers conducted a prespecified analysis of glycemic subgroups. Participants were divided into a subgroup without diabetes/normoglycemia (n = 1,175), prediabetes (n = 1,934) and type 2 diabetes (n = 3,150). Primary and secondary outcomes and event rates were compared between the subgroups.
“When our patients have diabetes and HF, they are at much higher risk,” Pardeep S. Jhund, PhD, MSc, BSc (Hons), MBChB, professor of cardiology and epidemiology at the University of Glasgow, U.K., said during the presentation. “HF is a terrible condition to have, not only in terms of quality of life and symptoms, but it really reduces life expectancy. In fact, life expectancy with HF is actually worse than many of the common cancers out there, despite our advances in treatment. Patients with diabetes are at a 60% higher risk for being hospitalized or having CV death than patients without diabetes.”
Dapagliflozin effective in all glycemia subgroups
In the overall DELIVER analysis, adults taking dapagliflozin had a reduced risk for worsening HF and CV death compared with placebo (HR = 0.82; 95% CI, 0.73-0.92; P = .0008). The findings were similar across all three glycemia subgroups, with those with type 2 diabetes having a 19% reduced risk for worsening HF or CV death with dapagliflozin compared with placebo (HR = 0.81; 95% CI, 0.69-0.95).
Adults using dapagliflozin had a lower risk for both worsening HF (HR = 0.79; 95% CI, 0.69-0.91; P = .001) and HF hospitalization (HR = 0.77; 95% CI, 0.67-0.89) compared with placebo, with no differences observed between any of the glycemia subgroups. For adults with type 2 diabetes, using dapagliflozin conferred a 17% reduced risk for worsening HF (HR = 0.83; 95% CI, 0.69-0.99) and a 19% lower risk for HF hospitalization (HR = 0.81; 95% CI, 0.67-0.98) compared with placebo. There was no significant difference in CV death between those taking dapagliflozin and those taking placebo in the overall study. The findings were the same regardless of glycemia subgroup.
“Looking at the treatment benefit of dapagliflozin vs. placebo by baseline HbA1c as a continuous variable, at least for the primary outcomes and the worsening HF secondary outcome, the drug behaves similarly across the entire spectrum of HbA1c,” Inzucchi said.
Among those with type 2 diabetes at baseline, the trial findings were similar regardless of diabetes duration or baseline HbA1c. Adults using sulfonylureas at baseline who took dapagliflozin had a lower risk for worsening HF and CV death than placebo (HR = 0.5; 95% CI, 0.35-0.72), and the risk was significantly lower than that observed in the dapagliflozin group who did not take sulfonylureas (P for interaction = .003). There were no other significant interactions for other medication classes used at baseline.
“We truly have, for the first time, the first foundational therapy in HF across the entire range of ejection fraction,” Mikhail Kosiborod, MD, FACC, FAHA, cardiologist at Saint Luke’s Mid America Heart Institute and professor of medicine at the University of Missouri-Kansas City School of Medicine, said during the presentation. “It’s the first class of agents we’ve ever been able to say this about. These agents reduce CV deaths and hospitalizations for HF across the range of ejection fractions. They improve symptoms, physical limitations and quality of life across the range of ejection fraction, all with a favorable safety profile.”
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Jhund P, et al. S55-A. Presented at: European Association for the Study of Diabetes Annual Meeting; Sept. 19-23, 2022; Stockholm (hybrid meeting).
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