KANSAS CITY, Mo. — DEFINE-HF (Dapagliflozin EFfect on symptoms and bIomarkers iN patiEnts with Heart Failure), a clinical study championed by Saint Luke’s Mid America Heart Institute, is the first randomized controlled trial to look at the early effects of SGLT2 inhibitors on symptom burden, physical limitations and quality of life in patients with heart failure and reduced left ventricular ejection fraction. DEFINE-HF was completed on May 31, 2019 and trial findings were presented publicly for the first time at the Heart Failure Society of America’s 23rd Annual Scientific Meeting Late-Breaking Clinical Trial Sessions on September 16, 2019 in Philadelphia, PA, and published simultaneously in Circulation.
Heart failure is the leading cause of hospitalizations in the United States and Western Europe. Patients with heart failure experience high burden of debilitating symptoms, and are at high risk of disease progression, repeat hospitalizations and death.
“The key goals of management in patients with heart failure include prolonging life and preventing hospital admissions; but another, equally important goal is reducing the symptom burden and physical limitations due to heart failure and improving the quality of life,” said Saint Luke’s cardiologist Mikhail Kosiborod, MD, study Chair and national principal investigator. “There is a substantial need to develop treatments that not only improve survival, but also positively impact the symptoms and functional status of patients with heart failure. The DEFINE-HF trial now demonstrates that treatment with dapagliflozin results in clinically meaningful improvements in heart failure-related health status, including symptoms, physical function, and quality of life, and, these effects emerge after just 12 weeks of treatment. Importantly, although dapagliflozin was initially developed as a treatment to lower blood glucose, in the DEFINE-HF Trial these beneficial effects on heart failure were consistent regardless of diabetes status”.
The DEFINE-HF clinical trial was designed to evaluate the effects of dapagliflozin 10 mg daily on heart failure biomarkers, symptoms, health status, and quality of life in patients with chronic heart failure and reduced left ventricular ejection fraction, with and without Type 2 diabetes. The 12-week randomized, double-blind, placebo-controlled trial recruited patients from 26 sites in 16 states across the US, with Saint Luke’s Mid America Heart institute being the leading recruiting hospital. Significantly greater proportions of patients treated with dapagliflozin experienced clinically meaningful improvements in heart failure related symptoms, functional status, and quality of life (measured by Kansas City Cardiomyopathy Questionnaire), or natriuretic peptides, as compared with placebo – which was consistent in patients with and without type 2 diabetes mellitus. There was no imbalance in safety events between dapagliflozin and placebo, although the number of events was small.
“These findings come on the heels of the DAPA-HF Trial, in which we observed that dapagliflozin substantially lowered the risk of heart failure hospitalization or death from cardiovascular causes, with a favorable safety profile,” said Kosiborod. “DEFINE-HF Trial compliments the findings of DAPA-HF by demonstrating beneficial effects of dapagliflozin on patients’ health status after just 12 weeks of therapy. Collectively, these data will likely have a significant impact on how we approach and treat this deadly disease in the future.”
DEFINE-HF was an investigator-initiated trial, with the concept developed, and trial sponsored and executed by the national coordinating center at Saint Luke’s Mid America Heart Institute in collaboration with the academic Executive Committee, independent of the funding source. The study was funded by AstraZeneca.
Dapagliflozin, which is manufactured and marketed by AstraZeneca, was approved by the FDA in January 2014 as a treatment for elevated glucose levels, along with diet and exercise, in adults with type 2 diabetes.
For more information about the study at Saint Luke’s, call 816-932-9858 or email DEFINE-HF@saint-lukes.org.
Saint Luke’s Mid America Heart Institute is a member of Saint Luke’s Health System, which consists of 18 area hospitals and several primary and specialty care practices, and provides a range of inpatient, outpatient, and home care services. Founded as a faith-based, not-for-profit organization, our mission includes a commitment to the highest levels of excellence in health care and the advancement of medical research and education. The health system is an aligned organization in which the physicians and hospitals assume responsibility for enhancing the physical, mental, and spiritual health of people in the metropolitan Kansas City area and the surrounding region.