AHA: Novel Drug Effective for Hyponatremia in Heart Failure Patients

November 15, 2006

CHICAGO -- Tolvaptan, an investigational selective oral vasopressin V2 -receptor antagonist, restored serum sodium concentrations in heart failure and cirrhosis patients with hyponatremia, researchers reported here.

CHICAGO, Nov. 15 -- Tolvaptan, an investigational selective oral vasopressin V2 -receptor antagonist, restored serum sodium concentrations in heart failure and cirrhosis patients with hyponatremia, researchers reported here.

Compared with placebo patients in randomized, double blind studies of patients with euvolemic or hypervolemic hyponatremia, serum sodium concentrations increased in the tolvaptan arm by day four and the rise was durable at 30 days (P

Among the findings:

  • Serum sodium concentrations were significantly higher in the tolvaptan group within eight hours of first administration and after the full 30 days of therapy (P0.5 mmol per liter per hour; maximum observed rate, 0.61 mmol per liter per hour). In only four patients (1.8%) was the predefined, potentially clinically important serum sodium concentration (>146 mmol per liter) exceeded.

In a NEJM editorial that accompanied the study, Richard M. Hays, M.D., of the Albert Einstein College of Medicine in New York, agreed that the results were encouraging. Yet he cautioned that the safety profile of the drug suggests the need for "careful oversight of the use of this agent is required, not only by means of frequent clinical visits and measurement of serum sodium, but also through daily measurement of body weight by patients."

Dr. Hays added that an important remaining question is the "extent to which added benefits might be realized if the V1A -mediated actions of vasopressin were brought under control with the use of combined V1A/V2-receptor antagonists."

Robert W. Schrier, M.D., of the University of Colorado, the lead author of the NEJM paper, reports having served as a consultant to Otsuka, Astellas, Bayer, and Amgen. Dr. Gheorghiade reports having served as a consultant to Otsuka, PDL, Sigma Tau, Medtronic, and GlaxoSmithKline and having received honoraria from Medtronic, Astra Zeneca, Scios, Glaxo Smith-Kline, Otsuka, PDL, Abbott, and Sigma Tau. Frank S. Czerwiec, M.D., and Cesare Orlandi, M.D., are employees of Otsuka Maryland Research Institute.