A multicenter study led by Vanderbilt University Medical Center (VUMC) and Lipscomb University College of Pharmacy in Nashville has identified a potential new treatment for acute heart failure, a leading cause of hospitalization and death. The drug, dapagliflozin, which was originally approved for Type 2 diabetes, has demonstrated benefits for patients with heart and chronic kidney disease, and heightened cardiovascular risk. The researchers found that dapagliflozin improves diuresis, the elimination of excess fluid from the lungs, thereby relieving congestion, and reducing hospital stays. This new treatment has the potential for an international impact on acute heart failure treatment.
Every year, 800,000 patients are admitted to U.S. hospitals with acute heart failure, putting them at high risk for prolonged hospital stays and death. The annual cost of treating acute heart failure in the United States is estimated to exceed $34 billion. Diuretic therapy is commonly used to improve symptoms and lung congestion caused by fluid buildup in patients with acute heart failure. However, the optimal approach to diuretic therapy remains poorly defined, contributing to high death and readmission rates. Many patients do not respond well to diuretics, leading to persistent congestion and readmission to the hospital soon after discharge.
Dapagliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor that acts on the kidneys to increase the removal of sodium and glucose from the body. A randomized, clinical trial of dapagliflozin in patients hospitalized with acute heart failure was initiated by VUMC in April 2020. Despite challenges presented by the COVID-19 pandemic, researchers were able to enroll 240 patients and complete the trial, showcasing the collaborative efforts between the CERI research team, emergency medicine, and cardiology departments. The trial demonstrated the safety and efficacy of early administration of dapagliflozin in reducing adverse events and hospital stay durations in patients with acute heart failure.
The trial enrolled patients at multiple sites in addition to VUMC within 24 hours of admission for acute heart failure. Patients were randomized to receive dapagliflozin or conventional diuretic treatment. While early administration of dapagliflozin did not improve diuretic efficiency compared to conventional treatment, patients who received the drug experienced shorter periods of IV diuresis and faster discharge during the five-day study period. This approach allows for the initiation of optimal outpatient therapy at discharge, reducing the risk of readmission. The study also highlighted the unique partnership and infrastructure in emergency medicine at VUMC, allowing for the design and conduct of impactful clinical trials in acute heart failure.
The research team at VUMC, including innovative contributors like JoAnn Lindenfeld, MD, Sean Collins, MD, and Zachary Cox, PharmD, were instrumental in the successful completion of the trial. The collaboration between multiple medical centers enabled the trial to move forward and demonstrate the potential benefits of dapagliflozin in acute heart failure treatment. The study, supported by AstraZeneca, was independently conducted by VUMC investigators and funded in part by the National Heart, Lung, and Blood Institute of the National Institutes of Health. Dapagliflozin, marketed under the brand name FARXIGA, has shown promise in improving outcomes for patients with acute heart failure, providing a potential new treatment option in the management of this serious condition.
