Efficacy and Safety of Tolvaptan in Heart Failure Patients with Sustained Volume Overload despite the Use of Conventional Diuretics: A Phase III Open-Label Study

Abstract

Purpose

Volume overload is a common complication associated with heart failure (HF) and is recommended to be treated with loop or thiazide diuretics. However, use of diuretics can cause serum electrolyte imbalances and diuretic resistance. Tolvaptan, a selective, oral, non-peptide vasopressin V2-receptor antagonist, offers a new option for treating volume overload in HF patients. The aim of this study was to investigate the efficacy and safety of tolvaptan in Japanese HF patients with volume overload.

Methods

Fifty-one HF patients with volume overload, despite using conventional diuretics, were treated with 15 mg/day tolvaptan for 7 days. If the response was insufficient at Day 7, tolvaptan was continued for a further 7 days at either 15 mg/day or 30 mg/day. Outcomes included changes in body weight, symptoms and safety parameters.

Results

Thirty-six patients discontinued treatment within 7 days, therefore 15 patients entered the second phase of treatment. In two patients, tolvaptan was increased to 30 mg/day after 7 days. Body weight was reduced on Day 7 (−1.95 ± 1.98 kg; n = 41) and Day 14 (−2.35 ± 1.44 kg; n = 11, 15 mg/day). Symptoms of volume overload, including lower limb edema, pulmonary congestion, jugular venous distention and hepatomegaly, were improved by tolvaptan treatment for 7 or 14 days. Neither tolvaptan increased the incidence of severe or serious adverse events when administered for 7–14 days.

Conclusions

This study confirms the efficacy and safety of 15 mg/day tolvaptan for 7–14 days in Japanese HF patients with volume overload despite conventional diuretics.

Appendix

The present study was conducted at the following institutions in Japan: National Hospital Organization Hakodate National Hospital, Hokkaido Prefectural Welfare Federation of Agricultural Cooperatives Sapporo Kosei General Hospital, National Hospital Organization Nishi Sapporo National Hospital, National Hospital Organization Tokyo Medical Center, Tokyo Medical University Hospital, Nihon University Itabashi Hospital, National Hospital Organization Takasaki General Medical Center, National Hospital Organization Saitama National Hospital, University of Yamanashi Hospital, Nagano Prefectural Federation of Agricultural Cooperatives for Health and Welfare Saku Central Hospital, Seirei Hamamatsu General Hospital, Mie University Hospital, Mie Prefectural General Medical Center, National Cerebral and Cardiovascular Center, Osaka Police Hospital, Osaka City General Hospital, Kansai Rosai Hospital, Nara Medical University Hospital, Hospital of Hyogo College of Medicine, Hyogo Prefectural Amagasaki Hospital, Tokushima University Hospital, National Hospital Organization Ureshino Medical Center, and Saiseikai Kumamoto Hospital.