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Dapagliflozin Effects on Biomarkers, Symptoms, and Functional Status in Patients with Heart Failure with Reduced Ejection Fraction: The DEFINE-HF Trial


Nassif, M. E., Windsor, S. L., Tang, F., Khariton, Y., Husain, M., Inzucchi, S. E., Mc-Guire, D. K., Pitt, B., Scirica, B. M., Austin, B., Drazner, M. H., Fong, M. W., Givertz, M. M., Gordon, R. A., Jermyn, R., Katz, S. D., Lamba, S., Lanfear, D. E., Larue, S. J., Lindenfeld, J., Malone, M., Marguiles, K., Mentz, R. J., Mutharasan, R. K., Pursley, M., Umpierrez, G., Kosiborod, M., Malik, A. O., Wenger, N., Ogunniyi, M., Vellanki, P., Murphy, B., Newman, J., Hartupee, J., Gupta, C., Goldsmith, M., Baweja, P., Montero, M., Gottlieb, S. S., Costanzo, M. R., Hoang, T., Warnock, A., Allen, L., Tang, W., Chen, H. H., Cox, J. M. (2019).

By Anne Li, Research Assistant

Published in Circulation (2019) and presented at the September 2019 Heart Failure Society of America annual meeting, the DEFINE-HF study aimed to investigate the effects of sodium-glucose co-transporter-2 inhibitors (SGLT-2i), such as dapagliflozin, in patients with heart failure with reduced ejection fraction (HFrEF). Heart failure (HF) is a leading cause of death globally, and HFrEF is especially debilitating. SGLT-2i are medications that are prescribed to treat type 2 diabetes mellitus, and have been supported by previous studies to reduce risk of
hospitalization for HF in patients with diabetes. However, it is unknown whether this class of medications is beneficial for treatment of HF and HFrEF, especially in patients without diabetes. Dr. Rita Jermyn, Director of the Center for Advanced Cardiac Therapeutics at St. Francis Hospital, made significant contributions to this first-of-its-kind, multicenter, randomized, double-blind, placebo-controlled trial. This groundbreaking study found that patients with heart failure with reduced ejection fraction, with or without diabetes, treated with dapagliflozin for 12 weeks, showed improvements in HF-related symptoms, functional status and quality of life, and natriuretic peptides. Thus,
SGLT-2i, such as dapagliflozin, can have an important role in treating heart failure, not only through improving
physiologic function, but also through enhancing quality of life. Patients who suffer from heart failure carry a burden that is likely to affect every aspect of their life, from not being able to enjoy activities that were once vital to their happiness, to frequently having to be hospitalized. This study demonstrates the potential of SGLT-2i to improve, if not transform, the lives of heart failure patients, and shows great promise in this class of medications originally developed to treat diabetes. Looking towards the future, this study can be re-designed to investigate even more population groups across different centers, and assess the effects of SGLT-2i on a long-term scale.