Dapagliflozin adds substantial improvements in symptoms, exercise function to demonstrated disease-modifying properties for patients with HFpEF.
Use of the SGLT-2 inhibitor dapagliflozin was associated with significant improvements in symptoms and physical limitations among patients with heart failure with preserved ejection fraction (HFpEF) according to results of the PRESERVED-HF trial presented at the Heart Failure Society of America (HFSA) Annual Scientific Meeting 2021.
Specifically, treatment with dapagliflozin resulted in clinically meaningful and statistically significant improvements in HF limitations measured by the Kansas City Cardiomyopathy Questionnaire clinical summary (KCCQ-CS) score and in exercise function as measured by 6-minute walking distance
“To our knowledge, PRESERVED-HF is the first trial to show compelling benefits of SGLT2 inhibitors on both patient-reported symptoms and physical limitations, as well as objectively measured physical function in individuals with HFpEF – outcomes of great importance to both patients and clinicians,” said Mikhail Kosiborod, MD, cardiologist at Saint Luke’s Mid America Heart Institute and Vice President of Research at Saint Luke’s Health System, in a St Luke's statement.
Kosiborod said the findings are particularly meaningful for HFpEF which he notes has been referred to as the “black hole” of cardiology because of the historic lack of effective treatments with disease modifying properties. “PRESERVED-HF,” he commented in the statement, “shows that dapagliflozin can enable individuals with HFpEF to feel better and do more within just 12 weeks.”
PRESERVED-HF, a multicenter, double-blind, randomized, placebo-controlled trial, assessed the use of dapagliflozin 10 mg vs matching placebo once daily for 12 weeks among 324 patients (162 in each arm) across 26 US sites. KCCQ clinical summary score at 12 weeks was the primary outcome of interest with 6-minute walking distance a key secondary endpoint.
Criteria for PRESERVED-HF inclusion were NYHA class II-IV symptoms, left ventricular ejection fraction (LVEF) of at least 45%, NTproBNP of ≥225 pg/mL, current diuretic therapy, and at least one of the following: recent HF hospitalization or urgent visit requiring IV diuretic, elevated filling pressures by right or left heart catheterization, or structural heart disease by echocardiography.
Average duration of HF was 3 years with median LVEF 60%. Mean age of study participants was 70 years; 57% were women, 30% were African American—both groups known to have high HFpEF symptom burden but traditionally to be under-represented in clinical trials, according to the St Lukes statement. Approximately half of participants had diabetes (56%) and atrial fibrillation (53%).
Investigators report that use of dapagliflozin was associated with significant improvements in symptoms and physical limitations measured by the KCCQ-CS—an increase of 5.8 points (95% CI, 2.3-9.2) at 12 weeks (P=.001) for total symptoms and increase of 5.3 points for physical limitations. Analysis for the secondary endpoint found dapagliflozin was associated with a significant improvement in 6-minute walking distance vs placebo—effect size, 20.1 meters (95% CI, 5.6-34.7; P =.007).
The study indicates the effect of dapagliflozin was consistent across subgroups, including those with type 2 diabetes, baseline LVEF, sex, race, and age.
No differences were observed between dapagliflozin and placebo groups in terms of natriuretic peptides, A1C, or systolic blood pressure. There was a modest weight reduction of 0.72 (95% CI, 0.01-1.42) kg observed with dapagliflozin versus placebo (P=.046)
“Taken together with the results of previous studies, our findings further strengthen the notion that SGLT2 inhibitors represent a disease-modifying therapy, and thus an important new treatment option for HFpEF, which is a highly morbid condition,” stated Kosiborod. “This is great news for patients and clinicians. As a cardiologist and researcher, I am excited about the potential impact of PRESERVED-HF data on the management of this patient population.”
This study, “Effects of Dapagliflozin on Symptoms, Function and Quality of Life in Patients with Heart Failure and Preserved Ejection Fraction - Main Results from the PRESERVED-HF Trial,” was presented at HFSA 2021.