Efficacy of oral tolvaptan in acute heart failure patients with hypotension and renal impairment

AIMS: Although congestion is the main reason for admission in patients with worsening acute heart failure syndromes, patients presenting with low SBP and renal impairment often do not respond adequately to and may not tolerate traditional diuretic therapy. We sought to determine the short-term hemodynamic effects of tolvaptan in this high-risk population. METHODS: In a subset analysis of the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan trial, 759 patients (18% of total) had elevated blood urea nitrogen (BUN) (> 20 mg/dl) and low SBP (<105 mmHg) at admission. Of these, 386 were randomized to tolvaptan and 373 to placebo. RESULTS: Demographics and baseline characteristics were similar in both groups. Greater reductions from baseline in body weight were observed for tolvaptan (1.63 ± 2.00 vs. 0.76 ± 1.75 kg, P < 0.0001 at day 1 and 3.23 ± 3.36 vs. 2.10 ± 3.47 kg, P < 0.0001 at day 7 or discharge). Greater increases in serum sodium concentration were also observed in the tolvaptan group as early as day 1 (4.41 ± 3.67 vs. 1.32 ± 3.93 mEq/l, P < 0.0001) and persisted through day 7 or discharge (4.79 ± 4.89 vs. 1.25 ± 5.00 mEq/l, P < 0.0001). Similarly, improvements in patient-reported dyspnea and investigator-assessed orthopnea were significantly greater in the tolvaptan group as early as day 1 of treatment. These changes were not associated with significant differences in heart rate, SBP, DBP or serum creatinine between patients in the two treatment groups during hospitalization. In-hospital mortality rates (total and cause-specific) were comparable to patients who had presented with SBP more than 105 mmHg and BUN less than 20 mg/dl. CONCLUSION: In this subgroup analysis of patients with hypotension and renal impairment, tolvaptan improved symptoms, reduced body weight and increased serum sodium as early as inpatient day 1 without adversely affecting blood pressure or renal function.