Acute Hemodynamic Effects of Tolvaptan, a Vasopressin V2 Receptor Blocker, in Patients With Symptomatic Heart Failure and Systolic DysfunctionAn International, Multicenter, Randomized, Placebo-Controlled Trial
James E. Udelson, MD*,*,
Cesare Orlandi, MD ,
John Ouyang, PhD,
Holly Krasa, MS,
Christopher A. Zimmer, MD,
Geir Frivold, MD ,
W. Herbert Haught, MD ,
Sheiba Meymandi, MD||,
Cezar Macarie, MD¶,
Dimitar Raef, MD#,
Patricia Wedge, RN, CCRC**,
Marvin A. Konstam, MD* and
Mihai Gheorghiade, MD
* Division of Cardiology, Tufts Medical Center, Boston, Massachusetts
Otsuka Pharmaceuticals Development and Commercialization, Rockville, Maryland
VA Loma Linda Healthcare System, Loma Linda, California
Oracle Research, Huntsville, Alabama
|| UCLA Medical Center, Los Angeles, California
¶ Institutul de Boli Cardiovasculare si Transplant Professor Iliescu, Bucharest, Romania
# Medical Institute-Ministry of Interior, Sofia, Bulgaria
** Cardiovascular Clinical Studies, Boston, Massachusetts
Division of Cardiology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois
View larger version (16K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 1 Mean Change from Baseline in PCWP and RAPs
(Top) Mean change from baseline in pulmonary capillary wedge pressure (PCWP) out to 8 h after treatment administration. The pairwise comparisons of 15, 30, and 60 mg tolvaptan versus placebo each showed a statistically significant decrease in peak change in PCWP from 3 to 8 h post-dose, the pre-specified time period for assessment. (Bottom) Mean change from baseline in right atrial pressure (RAP) in the 4 treatment groups. The tolvaptan 15- and 30-mg doses resulted in statistically significant reductions in peak change in RAP as compared with placebo.
|
|
View larger version (17K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 2 Mean Change From Baseline in Urine Volume and Osmolality
(Top) Mean change from baseline in urine volume in the first 8 h after treatment administration. A dose-dependent increase in urine output was observed among the tolvaptan-treated groups. (Bottom) Mean change from baseline in urine osmolality in the first 8 h after dosing. Urine osmolality was significantly reduced by all doses of tolvaptan relative to placebo (p < 0.0001 for all tolvaptan groups vs. placebo).
|
|
View larger version (16K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 3 Changes in Plasma Osmolality
Mean change from baseline in plasma osmolality (OSM) in the 4 treatment groups. A significant increase was observed in all of the tolvaptan dosing groups (p < 0.0005 for all tolvaptan groups vs. placebo at 4 h and later).
|
|
|
