PRESERVED-HF: Dapagliflozin Reduces Symptom Burden, Physical Limitations in HFpEF

Presented at HFSA 2021, PRESERVED-HF provides evidence suggesting dapagliflozin use was associated with improvements in KCCQ symptom score and 6-minute walking distance in patients with heart failure with preserved ejection fraction.

Results of PRESERVED-HF demonstrate use of dapagliflozin was associated with significant improvements in symptoms and physical limitations among patients with heart failure with preserved ejection fraction (HFpEF).

Presented at the Heart Failure Society of America (HFSA) Annual Scientific Meeting 2021, results of PRESERVED-HF indicate use of dapagliflozin was associated with clinically meaningful improvements in Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score and 6-minute walking distance, with these benefits evident after just 12 weeks.

“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. It is especially meaningful for this disease condition, as HFpEF has been called the “black hole” of cardiology because until now we have not been able to find efficacious, disease modifying treatments,” 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 statement. “PRESERVED-HF shows that dapagliflozin can enable individuals with HFpEF to feel better and do more within just 12 weeks.”

Funded by AstraZeneca, PRESERVED-HF was designed as a multicenter, double-blind, randomized, placebo-controlled trial with the specific intent of assessing use of dapagliflozin 10 mg against matching placebo once daily for 12 weeks. Conducted across 26 sites in the US, the trial randomized a population of 324 patients, with 162 to each arm, and had a primary end point of change in KCCQ-OS at 12 weeks.

To be included in the trial, patients needed to have heart failure with NYHA class II-IV symptoms, a left ventricular ejection fraction of 45% or greater, NTproBNP of 225 pg/mL or greater, a requirement for diuretic therapy, and at least one of the following: a recent heart failure hospitalization or urgent visit requiring IV diuretic, elevated filling pressures by right or left heart catheterization, or structural heart disease by echocardiography. Notable exclusion criteria included hospitalization for heart failure within the previous 7 days, an eGFR less than 20 mL/min/m2, a history of type 1 diabetes or diabetic ketoacidosis, and planned or recent PCI, CABG, valve surgery, or CRT.

During his presentation, Kosiborod noted 57% of trial participants were women and approximately 30% were African American, which the aforementioned release highlighted as understudied groups in HFpEF. Kosiborod also pointed out about half of the patients included in the trial had diabetes or atrial fibrillation.

Upon analysis, results indicated use of dapagliflozin was associated with significant improvements in symptoms and physical limitations measured by the KCCQ-OS, with an effect size of 5.8 (95% CI, 2.3-9.2) points at 12 weeks (P=.001). In a secondary analysis, results demonstrated use of dapagliflozin was associated with a significant improvement in 6-minute walking distance compared to placebo therapy, with results indicating a difference in effect size of 20.1 (95% CI, 5.6-34.7) meters (P =.007).

In a responder analysis, results suggested a greater proportion of patients on placebo therapy experienced deterioration r no change in KCCQ Clinical Summary Score at 12 weeks, while also demonstrating dapagliflozin use was associated with moderate-large or very large improvements (P=.01). In his presentation, Kosiborod highlighted no significant differences were observed for NTproBNP, BNP, HbA1c, or systolic blood pressure between the dapagliflozin and placebo arm of the study. Additionally, a modest weight reduction of 0.72 (95% CI, 0.01-1.42) kg was observed with dapagliflozin versus placebo therapy (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. 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,” Kosiborod added.

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.