Short-Term Effects of Tolvaptan in Patients With Acute Heart Failure and Volume Overload
Marvin A Konstam, Michael Kiernan, Arthur Chandler, Ravi Dhingra, Freny Vaghaiwalla Mody, Howard Eisen, W Herbert Haught, Lynne Wagoner, Divya Gupta, Richard Patten, Paul Gordon, Kenneth Korr, Russell Fileccia, Susan J Pressler, Douglas Gregory, Patricia Wedge, Douglas Dowling, Matthew Romeling, Jeremy M Konstam, Joseph M Massaro, James E Udelson, SECRET of CHF Investigators, Coordinators, and Committee Members, Marvin A Konstam, Michael Kiernan, Arthur Chandler, Ravi Dhingra, Freny Vaghaiwalla Mody, Howard Eisen, W Herbert Haught, Lynne Wagoner, Divya Gupta, Richard Patten, Paul Gordon, Kenneth Korr, Russell Fileccia, Susan J Pressler, Douglas Gregory, Patricia Wedge, Douglas Dowling, Matthew Romeling, Jeremy M Konstam, Joseph M Massaro, James E Udelson, SECRET of CHF Investigators, Coordinators, and Committee Members
Abstract
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 m2; 2) hyponatremia; or 3) diuretic resistance (urine output ≤125 ml/h following intravenous furosemide ≥40 mg). The primary endpoint was a 7-point change in self-assessed dyspnea at 8 and 16 h, using a novel standardized approach.
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).
Keywords: clinical trials; diuresis; dyspnea; jugular venous pressure; vasopressin antagonism.
Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Source: PubMed