Tolvaptan 30 mg/day did not improve day 1 dyspnea reduction compared to placebo in acute heart failure, despite significantly greater weight reduction (-2.4 kg vs -0.9 kg; p<0.001).
RCT (n=250)
Double-blind
Does tolvaptan added to background diuretic improve early dyspnea in patients with acute heart failure and volume overload?
In patients with acute heart failure, adding tolvaptan to background diuretics did not improve day 1 dyspnea despite producing significantly greater weight loss.
BACKGROUND: In patients with acute heart failure (AHF), dyspnea relief is the most immediate goal. Renal dysfunction, diuretic resistance, and hyponatremia represent treatment impediments. OBJECTIVES: It was hypothesized that the addition of tolvaptan to a background diuretic improved dyspnea early in patients selected for an enhanced vasopressin antagonism response. METHODS: In a double-blind trial, patients were randomized to tolvaptan 30 mg/day or placebo. Study entry required hospitalization within the previous 36 h, active dyspnea, and any of the following: 1) estimated glomerular filtration rate <60 ml/min/1.73 m RESULTS: We randomized 250 patients. There was no difference in the primary endpoint of day 1 dyspnea reduction, despite significantly greater weight reduction with tolvaptan (-2.4 ± 2.1 kg vs. -0.9 ± 1.8 kg; p < 0.001). At day 3, dyspnea reduction was greater with tolvaptan (p = 0.01). There were 2 significant treatment-by-subgroup interactions: patients without elevated jugular venous pressure and those without ascites showed directional favorability of tolvaptan over placebo for the primary endpoint compared with patients with these findings. CONCLUSIONS: Despite rapid and persistent weight loss with tolvaptan compared with placebo, in patients with AHF who were selected for greater potential benefit from vasopressin receptor inhibition, tolvaptan was not associated with greater early improvement in dyspnea. Apparent subsequent differences in dyspnea warrant further exploration of the temporal relationship between diuresis and dyspnea relief and a possible clinical role for tolvaptan. (Randomized, Double-Blind, Placebo Controlled Study of the Short Term Clinical Effects of Tolvaptan in Patients Hospitalized for Worsening Heart Failure With Challenging Volume Management SECRET of CHF; NCT01584557).
“There seems to be a temporal separation between differential fluid loss and dyspnoea improvement.”
Konstam et al. (Wed,) conducted a rct in Acute heart failure and volume overload (n=250). Tolvaptan vs. Placebo was evaluated on Day 1 dyspnea reduction. Tolvaptan 30 mg/day did not improve day 1 dyspnea reduction compared to placebo in acute heart failure, despite significantly greater weight reduction (-2.4 kg vs -0.9 kg; p<0.001).