A multicenter study led by Vanderbilt University Medical Center (VUMC) and Lipscomb University School of Pharmacy in Nashville has identified a potential new treatment for acute heart failure, a leading cause of hospitalization and death.
The drug, dapagliflozin, was initially approved for the treatment of type 2 diabetes, but has since been shown to reduce the risk of hospitalization for heart failure and death in patients with serious health problems including chronic heart and kidney disease and a increased cardiovascular risk. .
Reporting this month in the Journal of the American College of Cardiology, researchers found that dapagliflozin also benefits patients after hospital admission for acute heart failure. The drug improves diuresis, the removal of excess fluid from the lungs, thereby relieving congestion and may reduce hospital stays.
“We demonstrated the safety and efficacy of starting dapagliflozin within the first day of hospitalization for acute heart failure,” said the paper’s first author, Zachary Cox, PharmD, professor of Pharmacy Practice at Lipscomb University. This “will have an international impact on the treatment of acute heart failure.”
Each year, 800,000 patients with acute heart failure are admitted to American hospitals from emergency rooms. These patients are 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.
Diuretics are given to most patients with acute heart failure to improve symptoms and lung congestion caused by fluid buildup. However, the optimal approach to diuretic treatment in patients hospitalized for acute heart failure remains poorly defined and contributes to prolonged hospital stays and high rates of death and readmission.
Additionally, many patients do not respond to diuretics and approximately half of patients are discharged with persistent congestion. This can result in patients returning to the hospital shortly after discharge and being readmitted for further heart failure treatment.
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. In April 2020, VUMC began a randomized clinical trial of the drug in hospitalized patients with acute heart failure.
The study was designed by JoAnn Lindenfeld, MD, and Sean Collins, MD, MSc, of VUMC, and by Cox, a member of the VUMC heart failure research team.
Lindenfeld, professor of Medicine in the Division of Cardiology, is known nationally for her innovative contributions to the field of heart failure.
Collins, professor of Emergency Medicine, directs the Center for Emergency Care Research and Innovation (CERI), a national leader in emergency care research, co-directs the Vanderbilt Coordinating Center, which supports VUMC-led clinical research, and is director emergency medicine associate. trial research at the Vanderbilt Institute of Medicine and Public Health.
Cox is a member of the Heart Failure Society of America and has published extensively in this field.
Despite the COVID-19 pandemic, which reached its peak halfway through the study, the researchers were able to enroll 240 patients and complete the trial, “thanks to the diligent effort and collaboration between the CERI research team and… . emergency medicine and cardiology departments,” Cox said.
“This unique partnership allows VUMC to conduct trials in acute heart failure that are only possible at a small number of medical centers around the world,” he said.
The trial “really highlights the novelty of our Emergency Medicine infrastructure and why we are leaders in designing and conducting high-impact clinical trials like this one,” Collins added.
Patients were enrolled at five sites in addition to VUMC: TriStar Centennial Medical Center and Ascension St. Thomas Hospital West in Nashville, the University of North Carolina at Chapel Hill, the University of Mississippi Medical Center in Jackson, and INTEGRIS Medical Center Health Baptist in Oklahoma City.
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 weight-based diuretic efficiency compared with conventional treatment, patients receiving the drug experienced no increase in adverse events, required shorter periods of intravenous diuresis, and were discharged home. fastest over the five-day study period.
The trial demonstrated the safety and effectiveness of initiating a medication during early hospitalization that will continue to be prescribed upon discharge to help achieve optimal outpatient therapy and reduce the likelihood of readmission.
“It’s a way to improve diuresis AND begin to implement guideline-directed medical therapy in patients with acute heart failure,” Lindenfeld said.
Other VUMC co-authors are Cathy Jenkins, MS and Frank Harrell Jr., PhD, Department of Biostatistics, and Christina Kampe, MAcc, Karen Miller, RN, MPA, and William Stubblefield, MD, MPH, Department of Emergency Medicine.
The study was an investigator-initiated trial funded by AstraZeneca but conducted independently by VUMC researchers. Dapagliflozin is marketed under the brand name FARXIGA. Acute heart failure research at VUMC is supported in part by the National Heart, Lung, and Blood Institute of the National Institutes of Health.