medwireNews: Treatment with the sodium-glucose cotransporter (SGLT)2 inhibitor dapagliflozin improves symptoms and physical function in people with heart failure and preserved ejection fraction (HFpEF), suggest findings from the PRESERVED-HF trial.
Writing in Nature Medicine, Mikhail Kosiborod (Saint Luke’s Mid America Heart Institute, Kansas City, Missouri, USA) and co-investigators say that improving the health status measures of symptoms, functional status, and quality of life is “a key goal of HFpEF management,” but treatments tested to date “have had minimal impact on these key outcomes, highlighting a critical unmet need.”
For the phase 4 trial, 324 individuals with chronic, symptomatic HFpEF on standard therapy were randomly assigned to receive 12 weeks of once-daily treatment with dapagliflozin 10 mg or placebo. Participants were aged a median of 70 years and 57% were women, with a median BMI of 34.7 kg/m2, and 56% had type 2 diabetes. All participants had New York Heart Association class II–IV symptoms.
Mikhail Kosiborod outlines the findings from the PRESERVED-HF trial, demonstrating that dapagliflozin improves symptoms and physical function in people with heart failure with preserved ejection fraction, and discusses the promise of SGLT2 inhibitors for meeting the treatment goals in this population (9:35).
The average Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CS), a measure of HF-related health status, improved from 63.4 points at baseline to 68.6 points at week 12 in the dapagliflozin group, and from 61.8 to 62.8 points in the placebo arm, translating into a significant difference of 5.8 points favoring the SGLT2 inhibitor.
Kosiborod and team say that the observed KCCQ-CS benefits were due to significant improvements in the subdomains of symptoms and physical limitations. Moreover, benefits were “consistent across all prespecified subgroups, including patients with and without [type 2 diabetes] and those with ejection fraction above and below 60%,” they add.
Dapagliflozin treatment was also associated with a significantly greater improvement in average 6-minute walk test (6MWT) relative to placebo, with average improvements of 262 m and 242 m, respectively. This gave a “proportionally large” effect size of 20.1 m, given the “very low” baseline measures (median of 244 m in both groups), say the researchers.
“The observed improvement in 6MWT is relatively unique and highly clinically relevant,” they remark, noting that “[e]ven when patients with HFpEF are stable and well compensated, they have a markedly impaired objectively measured physical function.”
The investigators say that the safety profile of dapagliflozin in PRESERVED-HF was “generally consistent with previous SGLT2 inhibitor trials, with no new safety signals identified.” There were no cases of diabetic ketoacidosis, severe hypoglycemia, or lower limb amputation.
Kosiborod et al caution that the “relatively short duration of follow-up precludes assessment regarding the durability of the observed benefit on HF-disease-specific symptoms or functional status.”
Nevertheless, they believe that “even the short-term improvements in health status and exercise function shown here with dapagliflozin represent an important therapeutic advance given the lack of available effective treatments for HFpEF.”
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