Clinical and hemodynamic effects of bosentan dose optimization in symptomatic heart failure patients with severe systolic dysfunction, associated with secondary pulmonary hypertension--a multi-center randomized study.
OBJECTIVE
To evaluate the effects of bosentan on echo-derived hemodynamic measurements, and clinical variables in symptomatic heart failure (HF) patients.


METHODS
Multi- center, double-blind, randomized (2:1), placebo-controlled study comparing bosentan (8-125 mg b.i.d.) to placebo in patients with New York Heart Association class IIIb-IV HF, left ventricular ejection fraction <35% and systolic pulmonary artery pressure (SPAP) >40 mm Hg. Primary and secondary endpoints were change from baseline to 20 weeks in SPAP and cardiac index, respectively. Safety endpoints were treatment emergent adverse events (AEs), change in body weight, hemoglobin, hematocrit, systolic blood pressure and diuretic use.


RESULTS
Ninety-four patients enrolled: 60 to bosentan, 34 to placebo. There was no significant difference between the 2 arms in SPAP change (0.1 +/- 11.5 mm Hg , 95% confidence limit (CL) -5.4 to 5.2, p = 0.97), cardiac index shift (0.12 +/- 0.45, 95% CL -0.09 to 0.33 , p = 0.24 ) or any of the other 22 echocardiographic measurements obtained. Therapy-duration was longer in the placebo arm, while more patients in the bosentan arm experienced adverse and serious AEs.


CONCLUSIONS
In HF patients with left ventricular dysfunction and secondary pulmonary hypertension, bosentan did not provide any measurable hemodynamic benefit, and was associated with more frequent AEs, requiring drug discontinuation.
Kaluski
Edo
E
Department of Cardiology, University of Medicine and Dentistry, Newark, NJ 07101, USA. ekaluski@gmail.com
Cotter
Gad
G
Leitman
Marina
M
Milo-Cotter
Olga
O
Krakover
Ricardo
R
Kobrin
Isaac
I
Moriconi
Tina
T
Rainisio
Maurizio
M
Caspi
Avraham
A
Reizin
Leonardo
L
Zimlichman
Reuven
R
Vered
Zvi
Z
D000959:Antihypertensive Agents / Q000008:administration & dosage*; D000077300:Bosentan; D004311:Double-Blind Method; D005260:Female; D054143:Heart Failure, Systolic / Q000150:complications* / Q000000981:diagnostic imaging / Q000188:drug therapy*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000150:complications* / Q000188:drug therapy; D008297:Male; D012720:Severity of Illness Index; D013449:Sulfonamides / Q000008:administration & dosage*; D016896:Treatment Outcome; D014463:Ultrasonography; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy
D000959:Antihypertensive Agents; D013449:Sulfonamides; D000077300:Bosentan