PRESERVED-HF: Dapagliflozin improves HFpEF symptoms at 12 weeks
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Dapagliflozin improved symptoms and physical limitations in patients with HF with preserved ejection fraction, according to results from the PRESERVED-HF trial.
“The treatment effect was large, clinically meaningful and statistically significant,” 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 a presentation at the Heart Failure Society of America Annual Scientific Meeting. He noted the results were consistent regardless of diabetes status and ejection fraction.
Kosiborod and colleagues randomly assigned 324 patients (mean age, 70 years; 57% women; median BMI, 35 kg/m2) with NYHA class II to IV HF and ejection fraction at least 45% (median, 60%) to dapagliflozin (Farxiga, AstraZeneca) or placebo. The primary endpoint was Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary score at 12 weeks.
At 12 weeks, the mean KCCQ clinical summary score was higher in the dapagliflozin group compared with the placebo group (effect size, 5.8 points; P = .001), Kosiborod said during the presentation.
The dapagliflozin group also had a higher KCCQ total symptom score (effect size, 5.8 points; P = .003) and a higher physical limitation score (effect size, 5.3 points; P = .026) compared with the placebo group at 12 weeks, he said.
The results did not vary by age, sex, history of diabetes, ejection fraction ( 60% vs. > 60%) or other prespecified parameters (P for interaction for all > .05), Kosiborod said.
The dapagliflozin group also had a greater 6-minute walk test score at 12 weeks than the placebo group (effect size, 20.1 m; P = .007), he said.
When the researchers analyzed the proportion of patients with a clinically meaningful change in KCCQ clinical summary score at 12 weeks, they found the dapagliflozin group was more likely to improve in score and the placebo group was more likely to deteriorate in score (P = .01).
The KCCQ overall summary score at 12 weeks was higher in the dapagliflozin group vs. the placebo group (effect size, 4.5 points; P = .009), Kosiborod said.
There were no differences between the groups in N-terminal pro-B-type natriuretic peptide levels, BNP levels, HbA1c and systolic BP at 12 weeks, and the dapagliflozin group had modest weight loss compared with the placebo group (0.72 kg; P = .046), he said.
Safety events were similar between the groups, according to the researchers.
“Dapagliflozin significantly improved symptoms and physical limitations in patients with HFpEF in just 12 weeks,” Kosiborod said during the presentation. “The goals of treatment in HFpEF and heart failure, in general, in addition to reducing deaths and hospitalization, include enabling patients to feel better and do more. PRESERVED-HF, to our knowledge, is the first trial to demonstrate that the SGLT2 inhibitor dapagliflozin significantly improves symptoms, physical limitations and 6-minute walking distance in patients with HFpEF, with a benefit at 12 weeks. These findings are highly complementary to those of large outcomes trials and collectively support the use of SGLT2 inhibitors as a new treatment option in HFpEF, which is a morbid condition with few therapeutic options.”
The DELIVER trial of dapagliflozin assessing clinical outcomes in patients with HFpEF is scheduled to be published in 2022.
In a discussion after the presentation, Milton Packer, MD, Distinguished Scholar in Cardiovascular Science at Baylor University Medical Center and visiting professor at Imperial College London, called the results “unprecedented.”
“This is the largest KCCQ benefit ever reported in any trial with a drug for HF (with reduced EF) or HFpEF,” he said. “The size of the effect and the consistency of the effect are really impressive, especially if you’re getting this at a time when there is no change in natriuretic peptides.”
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Kosiborod M, et al. Late-Breaking Clinical Trials I. Presented at: Heart Failure Society of America Annual Scientific Meeting; Sept. 10-13, 2021; Denver (hybrid meeting).
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