The effects of tolvaptan dose on cardiac mortality in patients with acute decompensated heart failure after hospital discharge.

Tolvaptan (TLV) is a newly developed oral vasopressin-2 receptor antagonist that is mostly used for patients with acute decompensated heart failure (ADHF) refractory to conventional diuretic therapy. The aim of this study was to investigate the effects of outpatient TLV dose on cardiac mortality in patients discharged after hospitalization for ADHF. One hundred and five patients with ADHF who had been treated with TLV for the first time during hospitalization were retrospectively divided into three groups based on outpatient TLV use and dose. The non-TLV group comprised patients who were not treated with TLV after discharge (n = 36). Patients who continued TLV after discharge were further classified into two groups: low-dose (LD)-TLV (3.75 mg/day, n = 27) and high-dose (HD)-TLV (7.5 or 15 mg/day, n = 42). The primary endpoint was cardiac mortality. Secondary endpoint included the composite of all-cause mortality or re-hospitalization due to worsening of ADHF. There were no significant differences in demographic variables other than body mass index (p = 0.0026), echocardiographic data, laboratory data other than serum chloride before TLV administration (p = 0.041), serum sodium (p = 0.040) and potassium (p = 0.027) at discharge, and concomitant medications among the three groups. The Kaplan-Meier curve showed that the survival rate was lower in HD-TLV than in non-TLV, whereas LD-TLV showed the highest survival rate among the three groups (p = 0.0001). Multivariable Cox regression analysis of the clinical characteristics used for predicting cardiac mortality revealed that LD-TLV (hazard ratio [HR] 0.16, 95% confidence interval [CI] 0.01-0.93, p = 0.040) and HD-TLV (HR 2.43, 95% CI 1.06-6.26, p = 0.035) were significant predictors after adjustment for predictive covariates. In conclusion, the judgement of the continuation of LD-TLV according to patient hemodynamics and severity of congestion may not cause worsened prognosis.