The Efficacy and Safety of Short-Term Tolvaptan Usage in Patients with Acute Decompensated Heart Failure

Abstract

Background: Patients admitted with acute decompensated heart failure (ADHF) have a poor prognosis and poor quality of life due to dyspnea and edema. Tolvaptan, a vasopressin V2 receptor antagonist, is an effective water diuretic. This study aimed to evaluate the efficacy and safety of a short course of tolvaptan to treat volume overload in patients with ADHF.

Methods: We conducted a phase III, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of a short course of tolvaptan (15 mg/day for 4 days) in hospitalized ADHF patients with volume overload despite the use of conventional diuretics. The primary end-point was the change in body weight after 4 days of treatment. The secondary end-points were the change in intake/output balance, change in serum sodium/potassium concentrations, physician/patient assessed signs and symptoms of heart failure after 4 days of treatment, and all-cause mortality in 1 month.

Results: A total of 110 patients were screened, and 91 were randomized to receive 15 mg/day of tolvaptan for 4 days (n = 46) or matching placebo (n = 45). Compared to the placebo-treated patients, tolvaptan significantly reduced body weight (-1.36 ± 2.13 kg in the tolvaptan group vs. -0.59 ± 1.27 kg in the placebo group, p = 0.0394). The tolvaptan group also had a negative intake/urine volume balance compared to the placebo group (-509.3 ± 2788.2 ml vs. 975.5 ± 1903.1 ml, p = 0.0059). The safety profile of tolvaptan was acceptable.

Conclusions: Tolvaptan significantly reduced volume overload in hospitalized ADHF patients with volume overload despite the use of conventional diuretics.

Keywords: ADHF; Diuretic; Heart failure; Tolvaptan.

Figure 1

The flow chart of the study. * DV: protocol deviation. Only for patients who were withdrawn early from study treatment prior to day 4. Examinations were performed at any time but no later than 3 days after the last dose of the investigational drug. ** Follow-up for the occurrence of serious adverse events 14 (±3) days and 28 (±3) days after receiving the final study drug dose by telephone contact. HF, heart failure.

Figure 2

The efficacy of tolvaptan for fluid management. (A) Body weight change. (B) Serum sodium concentration change in the two groups. Data are expressed as means with 95% confidence intervals. EOS, end of study, the data represented with the result after 4-day tolvaptan treatment analyzed with the last observation carried forward (LOCF) method.