Abstract
Background: Increased vasopressin levels may be present in patient with chronic heart failure (HF) and contribute to pathophysiology through effects on the vasopressin V2 receptor. The presence of background diuretic therapy may confound evaluations of vasopressin receptor antagonists (VRA). Methods and Results: Eligible patients had HF (New York Heart Association Class II-III), systolic dysfunction (left ventricular ejection fraction ≤0.40) and signs of congestion (eg, edema, rales). At screening, patients were removed from baseline diuretic therapy and placed on a low-sodium diet (2 g/day). After a 2-day run-in period, 83 patients were randomized to placebo (n = 21), monotherapy with the vasopressin V2 receptor antagonist tolvaptan (TLV) 30 mg (n = 20), monotherapy with furosemide 80 mg (FURO, n = 22) or both TLV 30 mg and FURO 80 mg (n = 20) once daily for 7 days. Patients were on standard background therapy and not fluid-restricted throughout the study. A decrease in body weight of -1.37 ± 1.61, -0.54 ± 1.59, and -1.13 ± 1.49 kg was observed versus baseline for TLV, FURO, and TLV+FURO, respectively, at day 8. At the same point, the placebo group showed a body weight increase of +0.72 ± 2.42 kg versus baseline (P =.0006 for TLV versus placebo). Increases in urine volume from baseline were greater with TLV alone (2646 ± 1503 mL/24 hours) than with FURO (894 ± 853 mL/24 hours, P <.001), or PLC (423 ± 786 mL/24 hours, P <.001), and similar to TLV+FURO (2585 ± 2119 mL/24 hours). An increase in serum sodium within the normal range was also observed in TLV-treated patients (P <.02 versus placebo; P <.01 versus FURO). No changes in serum potassium, other laboratory values, or blood pressure were observed. TLV therapy was well tolerated. Conclusions: In patients with HF and signs of volume overload, TLV monotherapy without concomitant loop diuretic therapy reduced body weight when compared to placebo without adverse changes in serum electrolytes, during a sodium restricted diet while on background medications including angiotensin-converting enzyme inhibitors and β-blockers.
| Original language | English |
|---|---|
| Pages (from-to) | 973-981 |
| Number of pages | 9 |
| Journal | Journal of Cardiac Failure |
| Volume | 17 |
| Issue number | 12 |
| DOIs | |
| State | Published - Dec 1 2011 |
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Keywords
- diuretics
- Heart failure
- vasopressin
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
Cite this
A multicenter, randomized, double-blind, placebo-controlled study of tolvaptan monotherapy compared to furosemide and the combination of tolvaptan and furosemide in patients with heart failure and systolic dysfunction. / Udelson, James E.; Bilsker, Martin S; Hauptman, Paul J.; Sequeira, Rafael; Thomas, Ignatius; O'Brien, Terrence; Zimmer, Christopher; Orlandi, Cesare; Konstam, Marvin A.
In: Journal of Cardiac Failure, Vol. 17, No. 12, 01.12.2011, p. 973-981.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A multicenter, randomized, double-blind, placebo-controlled study of tolvaptan monotherapy compared to furosemide and the combination of tolvaptan and furosemide in patients with heart failure and systolic dysfunction
AU - Udelson, James E.
AU - Bilsker, Martin S
AU - Hauptman, Paul J.
AU - Sequeira, Rafael
AU - Thomas, Ignatius
AU - O'Brien, Terrence
AU - Zimmer, Christopher
AU - Orlandi, Cesare
AU - Konstam, Marvin A.
PY - 2011/12/1
Y1 - 2011/12/1
N2 - Background: Increased vasopressin levels may be present in patient with chronic heart failure (HF) and contribute to pathophysiology through effects on the vasopressin V2 receptor. The presence of background diuretic therapy may confound evaluations of vasopressin receptor antagonists (VRA). Methods and Results: Eligible patients had HF (New York Heart Association Class II-III), systolic dysfunction (left ventricular ejection fraction ≤0.40) and signs of congestion (eg, edema, rales). At screening, patients were removed from baseline diuretic therapy and placed on a low-sodium diet (2 g/day). After a 2-day run-in period, 83 patients were randomized to placebo (n = 21), monotherapy with the vasopressin V2 receptor antagonist tolvaptan (TLV) 30 mg (n = 20), monotherapy with furosemide 80 mg (FURO, n = 22) or both TLV 30 mg and FURO 80 mg (n = 20) once daily for 7 days. Patients were on standard background therapy and not fluid-restricted throughout the study. A decrease in body weight of -1.37 ± 1.61, -0.54 ± 1.59, and -1.13 ± 1.49 kg was observed versus baseline for TLV, FURO, and TLV+FURO, respectively, at day 8. At the same point, the placebo group showed a body weight increase of +0.72 ± 2.42 kg versus baseline (P =.0006 for TLV versus placebo). Increases in urine volume from baseline were greater with TLV alone (2646 ± 1503 mL/24 hours) than with FURO (894 ± 853 mL/24 hours, P <.001), or PLC (423 ± 786 mL/24 hours, P <.001), and similar to TLV+FURO (2585 ± 2119 mL/24 hours). An increase in serum sodium within the normal range was also observed in TLV-treated patients (P <.02 versus placebo; P <.01 versus FURO). No changes in serum potassium, other laboratory values, or blood pressure were observed. TLV therapy was well tolerated. Conclusions: In patients with HF and signs of volume overload, TLV monotherapy without concomitant loop diuretic therapy reduced body weight when compared to placebo without adverse changes in serum electrolytes, during a sodium restricted diet while on background medications including angiotensin-converting enzyme inhibitors and β-blockers.
AB - Background: Increased vasopressin levels may be present in patient with chronic heart failure (HF) and contribute to pathophysiology through effects on the vasopressin V2 receptor. The presence of background diuretic therapy may confound evaluations of vasopressin receptor antagonists (VRA). Methods and Results: Eligible patients had HF (New York Heart Association Class II-III), systolic dysfunction (left ventricular ejection fraction ≤0.40) and signs of congestion (eg, edema, rales). At screening, patients were removed from baseline diuretic therapy and placed on a low-sodium diet (2 g/day). After a 2-day run-in period, 83 patients were randomized to placebo (n = 21), monotherapy with the vasopressin V2 receptor antagonist tolvaptan (TLV) 30 mg (n = 20), monotherapy with furosemide 80 mg (FURO, n = 22) or both TLV 30 mg and FURO 80 mg (n = 20) once daily for 7 days. Patients were on standard background therapy and not fluid-restricted throughout the study. A decrease in body weight of -1.37 ± 1.61, -0.54 ± 1.59, and -1.13 ± 1.49 kg was observed versus baseline for TLV, FURO, and TLV+FURO, respectively, at day 8. At the same point, the placebo group showed a body weight increase of +0.72 ± 2.42 kg versus baseline (P =.0006 for TLV versus placebo). Increases in urine volume from baseline were greater with TLV alone (2646 ± 1503 mL/24 hours) than with FURO (894 ± 853 mL/24 hours, P <.001), or PLC (423 ± 786 mL/24 hours, P <.001), and similar to TLV+FURO (2585 ± 2119 mL/24 hours). An increase in serum sodium within the normal range was also observed in TLV-treated patients (P <.02 versus placebo; P <.01 versus FURO). No changes in serum potassium, other laboratory values, or blood pressure were observed. TLV therapy was well tolerated. Conclusions: In patients with HF and signs of volume overload, TLV monotherapy without concomitant loop diuretic therapy reduced body weight when compared to placebo without adverse changes in serum electrolytes, during a sodium restricted diet while on background medications including angiotensin-converting enzyme inhibitors and β-blockers.
KW - diuretics
KW - Heart failure
KW - vasopressin
UR - http://www.scopus.com/inward/record.url?scp=84855950434&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84855950434&partnerID=8YFLogxK
U2 - 10.1016/j.cardfail.2011.08.005
DO - 10.1016/j.cardfail.2011.08.005
M3 - Article
C2 - 22123358
AN - SCOPUS:84855950434
VL - 17
SP - 973
EP - 981
JO - Journal of Cardiac Failure
JF - Journal of Cardiac Failure
SN - 1071-9164
IS - 12
ER -