KANSAS CITY, Mo. — Today, the findings of the PRESERVED-HF trial, offering potential new hope for people struggling with heart failure with preserved ejection fraction (HFpEF), are published in the journal, Nature Medicine.
"It is very rewarding to see the full results of our trial in print," said Mikhail Kosiborod, MD, Vice President of Research at Saint Luke's Health System, cardiologist at Saint Luke's Mid America Heart Institute, and the principal investigator of PRESERVED-HF. "For decades, we have been looking for treatments that could enable individuals living with HFpEF to feel better and do more—and finally, that search has produced really positive results."
6.2 million people in the United States are living with heart failure, and the majority are diagnosed with HFpEF. Individuals with HFpEF experience a heavy burden of debilitating symptoms and physical limitations, and a poor quality of life because of their disease. To date, there have been no pharmaceutical treatments that have demonstrated a compelling benefit on these important outcomes, highlighting a critical unmet need.
Sodium glucose cotransporter 2 (SGLT2) inhibitors are a class of agents that have been shown to reduce the risk of hospitalizations for heart failure, but their effects on symptoms, physical limitations and exercise function in HFpEF remain uncertain. The Effects of Dapagliflozin on Symptoms and Functional Status in Patients With Heart Failure and Preserved Ejection Fraction (PRESERVED-HF) was an investigator-initiated, randomized trial which recruited patients with chronic HFpEF across 26 centers in the United States, and randomly assigned treatment with either the SGLT2 inhibitor dapagliflozin, or placebo for 12 weeks. The primary endpoint was Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CS), a well-validated measure of heart failure related symptoms and physical limitations. Exercise function, measured by the 6-minute walking distance, was one of the secondary endpoints. Participants in the trial were representative of individuals with HFpEF in the US, with high burden of symptoms and significant impairment in physical function. Of note, 57% of trial participants were women, and over 30% were African American; two groups that are greatly impacted by HFpEF but are traditionally under-represented in clinical trials.
PRESERVED-HF results revealed that treatment with dapagliflozin substantially improved symptoms and physical limitations measured by the KCCQ-CS by 5.8 points (95% Confidence Interval 2.3 – 9.2), which was clinically meaningful, statistically significant (P value 0.001), and consistent across all pre-specified subgroups. In addition, dapagliflozin significantly improved objectively measured exercise function, represented by the 6-minute walking distance, by 20.1 meters (95% confidence interval 5.6 – 34.7, P value 0.007). Dapagliflozin was well tolerated, with no new safety signals identified.
“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,” Dr. Kosiborod said. “PRESERVED-HF shows that dapagliflozin can enable individuals with HFpEF to feel better and do more within just 12 weeks. 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”.
About HFpEF: In HFpEF, a patient’s heart has a preserved pumping function, but the heart’s relaxation is adversely affected due to multiple mechanisms, including inflammation, fibrosis, and endothelial dysfunction This ultimately leads to elevated filling pressures, and multiple symptoms such as breathlessness and exertional intolerance, as well as significant physical limitations, poor quality of life, and high risk of hospitalizations and death. While there are numerous treatments for patients with heart failure with reduced ejection fraction, clinicians have been limited in their ability to find efficacious treatments for individuals with HFpEF.
About PRESERVED-HF: This multi-center, double blind, randomized, placebo-controlled trial assigned 324 patients across 26 clinical trial sites in the U.S to take 10 mg. of dapagliflozin or a matching placebo once daily for 12 weeks. KCCQ-CS and a six-minute walk test were pre-specified as the primary and one of the secondary endpoints, respectively. PRESERVED-HF was an investigator-initiated trial funded by AstraZeneca and conducted by Saint Luke’s Mid America Heart Institute independent of the funding source. The full study results were presented as a late breaking clinical trial at the Heart Failure Society of America Scientific Sessions on September 12, 2021 and are in press in the journal, Nature Medicine.
About Saint Luke’s Mid America Heart Institute: Saint Luke’s Mid America Heart Institute, a member of Saint Luke’s Health System and a teaching affiliate of the University of Missouri-Kansas City, is one of the preeminent cardiovascular programs in the country. Its legacy of innovation began more than 35 years ago when it opened as the nation’s first heart hospital. Since then, the Heart Institute has earned a world-wide reputation for excellence in the treatment of heart disease, including interventional cardiology, cardiovascular surgery, imaging, heart failure, transplant, heart disease prevention, women’s heart disease, electrophysiology, outcomes research, and health economics. With more than 60 full-time board certified cardiovascular specialists on staff, the Heart Institute offers one of the largest heart failure/heart transplant programs in the country, has the largest experience with transcatheter aortic valve replacement in the Midwest, and is a global teaching site for the newest approaches to opening challenging blocked arteries using minimally invasive techniques.