NEW ORLEANS, La. (March 25, 2007) -- A diagnosis of worsening acute decompensated heart failure (ADHF) is characterized by the development of dyspnea (shortness of breath) associated with the rapid accumulation of fluid in the lungs. Patients who are hospitalized with ADFA need rapid and sustained improvements in fluid retention without risking renal dysfunction or depletion of electrolytes caused by dehydration. Tolvaptan, an oral nonpeptide vasopressin V2-receptor blocker, has been shown to achieve rapid and sustained results in this patient population, according to a study presented today at the American College of Cardiology’s 56th Annual Scientific Session. ACC.07 is the premier cardiovascular medical meeting, bringing together cardiologists and cardiovascular specialists to further breakthroughs in cardiovascular medicine. The study will be simultaneously published in the Journal of the American Medical Association (JAMA) and will appear in the March 28 print issue.
The vasopressin V2-receptor, a neural hormone in the body, is responsible for increased fluid retention. Fluid retention is the primary cause of hospitalization among ADHF patients over the age of 65, with more than one million hospitalizations reported each year. Previous research indicates that current treatments for these patients have significant safety concerns and are often inadequate in managing fluid retention, with common reports of electrolyte abnormalities and impaired kidney function.
The vasopressin V2-receptor blocker, tolvaptan, was used in this program of investigations, known as EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study with Tolvaptan). The international, multi-center study conducted at 359 centers in 20 countries was designed to evaluate tolvaptan's impact on short-term clinical status and long-term clinical outcomes, as well as safety profile, in patients hospitalized with ADHF.
The 4,133 patients enrolled in the trial within 48 hours of hospitalization were randomized to oral tolvaptan at 30 mg/day (n=2,072) or placebo (n= 2,061). Sites were assigned into one of two identical trials of 2,048 and 2,085 patients, respectively, to measure changes in patient-assessed global clinical status from baseline (using a visual analog scale to determine the degree of stimuli a patient is experiencing) and in body weight at day seven or at discharge (whichever came first). Additionally, the team measured changes in patient-assessed dyspnea at day one and physician-assessed edema (fluid build-up) at day seven or discharge if earlier. All 4,133 patients were combined into a long-term outcome trial, examining the long-term effects of tolvaptan on the endpoints of all-cause mortality and the combination of cardiovascular mortality or heart failure hospitalization. Final data and results from the EVEREST trial will be presented at the meeting.
"There is great interest in evidence-based treatments for patients hospitalized with worsening heart failure, as existing data with currently available treatments leave doubt regarding both efficacy and safety," said Marvin A. Konstam, M.D., of Tufts-New England Medical Center and lead author of the study.
"The EVEREST trial supports an important role for tolvaptan in managing patients with heart failure and volume overload."
Dr. Konstam will present this, "Effects of Vasopressin Receptor Antagonism With Tolvaptan on Clinical Status, Morbidity and Mortality in Patients Hospitalized With Acute Decompensated Heart Failure: Results of the EVEREST Trial," study on Sunday, March 25 at 8:50 a.m. in Hall A.
The American College of Cardiology (www.acc.org) represents the majority of board certified cardiovascular physicians in the United States. Its mission is to advocate for quality cardiovascular care through education, research, promotion, development and application of standards and guidelines- and to influence health care policy. ACC.07 and the i2 Summit is the largest cardiovascular meeting, bringing together cardiologists and cardiovascular specialists to share the newest discoveries in the treatment and prevention, while helping the ACC achieve its mission to address and improve issues in cardiovascular medicine.
Journal
JAMA