This article summarizes recent literature surrounding the use of tolvaptan for acute heart failure.
Elevated ventricular filling pressures (ie, congestion) are the primary reason for hospitalization in patients with acute heart failure (AHF). Despite the use of diuretics and vasodilators targeting decongestion, congestion persists in many AHF patients at hospital discharge and has been associated with increased morbidity and mortality. Furthermore, many patients with AHF are relatively resistant to the effect of loop diuretics, particularly those with chronic kidney disease and hyponatremia.
The oral vasopressin-2 receptor antagonist tolvaptan inhibits the action of antidiuretic hormone and leads to the loss of free water (aquaresis) in patients with HF. The large-scale Efficacy of Vasopressin Antagonist in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial failed to demonstrate the superiority of tolvaptan over placebo in terms of long-term clinical outcomes, yet patients randomized relatively early during their hospitalization were more likely to show improvement in symptoms with tolvaptan. These data suggest the hypothesis that in select AHF patients, early treatment with tolvaptan in addition to loop diuretics may improve congestion and, therefore, may improve the symptoms of AHF. This hypothesis was put to the test in the recently conducted Targeting Acute Congestion with Tolvaptan in Congestive Heart Failure (TACTICS-HF) trial.1
This study randomized 257 patients within 24 hours of acute HF presentation to either 30 mg of tolvaptan or a placebo. The proportion of patients defined as responders (having a significant improvement in dyspnea without the need for rescue therapy or death) at 24 hours was 16% for tolvaptan and 20% for placebo. Dyspnea relief by Likert scale was similar between tolvaptan and placebo at 8 hours and at 24 hours. Need for rescue therapy was also similar at 24 hours.
Results showed that tolvaptan did result in greater weight loss and net fluid loss as well as trends toward greater dyspnea improvement at 48 and 72 hours. However, patients treated with tolvaptan were more likely to experience worsening renal function during treatment. There were no differences in length of stay or post-discharge outcomes out to 30 days between the tolvaptan and placebo groups.
The findings echo earlier data demonstrating a disconnect between short-term fluid and weight loss and improvements in long-term clinical outcomes. However, the authors noted that it’s unclear whether this suggests that short-term decongestion is unrelated to long-term outcomes or that available therapies for decongestion are unable to alter longer-term outcomes. At the current cost of tolvaptan in the United States ( approximately $1200 for the 48-hour treatment tested in the TACTICS trial), the added value of this therapy in the clinical setting of AHF wouldn’t appear justified, nor would the present data seem to support an expansion of the role of tolvaptan in patients with AHF beyond the current FDA indication for hyponatremia.
Authors of an accompanying editorial noted that the TACTICS-HF trial “is an important report and perhaps the final dialogue for the drug tolvaptan and its role in HF.”2 They suggested that there’s no justification for additional study of tolvaptan’s effectiveness in acute or chronic HF. Further, they recommend that the use of tolvaptan be discouraged due to its lack of efficacy and high cost.