ORLANDO, Fla. — The addition of tolvaptan to a standard furosemide regimen did not improve congestion at 24 hours in patients hospitalized with acute HF, according to a late-breaking presentation at the Heart Failure Society of America Scientific Assembly.
According to the results of the TACTICS-HF trial, presented by Robert Mentz, MD, from Duke Clinical Research Institute, while treatment of patients with tolvaptan (Samsca, Otsuka Pharmaceuticals) conferred greater weight loss and net fluid loss compared with placebo, patients assigned tolvaptan were also more likely to experience decline in renal function during treatment.
For the double blind, placebo-controlled TACTICS-HF trial, researchers randomly assigned 257 patients (mean age, 66 years) within 24 hours of acute HF presentation to tolvaptan 30 mg or placebo, which was given at baseline, 24 hours and 48 hours. All patients received a fixed-dose furosemide regimen as background therapy.
All patients had dyspnea at rest with minimal exertion, N-terminal pro-B type natriuretic peptide levels >2000 pg/mL and at least one symptom or sign of congestion.
The primary endpoint was response to therapy at 8 hours and 24 hours as determined by the seven-point Likert dyspnea relief scale without death or the need for rescue therapy at 24 hours.
The primary endpoint occurred in 16% of the tolvaptan group and 20% of the placebo group (P = .32), according to the researchers.
There were also no differences in moderate or marked dyspnea relief according to the Lykert scale at 8 hours (tolvaptan, 25%; placebo, 28%; P = .59) or at 24 hours (tolvaptan, 50%; placebo, 47%; P = .8), Mentz and colleagues found. They also found the need for rescue therapy at 24 hours was 21% in the tolvaptan group and 18% in the placebo group (P = .57).
While the tolvaptan group had greater weight loss and greater net fluid loss than the placebo group, those patients also were more likely to have worsening renal function, defined as change in serum creatinine of at least 0.3 mg/dL in 72 hours (39% vs. 27%; P = .037), according to Mentz and colleagues.
Randall C. Starling
“While addition of tolvaptan to a standardized furosemide regimen did not improve the proportions of patients classified as responders at 24 hours, it did improve weight loss and fluid loss [and] increased worsening renal function during treatment. However, changes were generally modest, and resulted in trends toward improved dyspnea relief and a greater proportion of responders at 48 and 72 hours,” Mentz said during the presentation.
The results were simultaneously published in the Journal of the American College of Cardiology. In a related editorial published there, Randall C. Starling, MD, MPH, FACC, FESC, James B. Young, MD, both medical directors of the Kaufman Center for Heart Failure, Cleveland Clinic, wrote “It may be time to abandon the dyspnea endpoint in acute [HF] trials based on the difficulty of the measure and the uncertainty of its significance.”
James B. Young
The study “provides extremely important data for clinicians and proves clearly that there is no benefit to the use of tolvaptan and its use should be discouraged based upon lack of efficacy and cost. The unmet need to develop better strategies for the treatment of acute heart failure remains a challenge and mandates ongoing investigation,” Starling and Young, editor of the Cardiology Today HF and Transplantation section, wrote. – by Dave Quaile
Mentz R, et al. Late-Breaking Clinical Trials. Presented at: Heart Failure Society of America Scientific Assembly; Sept. 17-20, 2016; Orlando, Fla.
Felker MG, et al. J Am Coll Cardiol. 2016;doi:10.1016/j.jacc. 2016.09.004.
Starling RC, Young JB. J Am Coll Cardiol. 2016;doi:10.1016/j.jacc. 2016.09.005.
TACTICS-HF was an investigator-initiated study funded by Otsuka Pharmaceuticals. Mentz reports receiving research support from Amgen, AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Gilead, Medtronic, Novartis, Otsuka and ResMed; receiving honoraria from HeartWare, Janssen, Luitpold, Novartis, ResMed and Thoratec/St. Jude Medical; and serving on advisory boards for Boehringer Ingelheim and Luitpold. Starling and Young report no relevant financial disclosures.