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

Cardiology. 2008;109(4):273-80. doi: 10.1159/000107791. Epub 2007 Sep 17.


Objective: To evaluate the effects of bosentan on echo-derived hemodynamic measurements, and clinical variables in symptomatic heart failure (HF) patients.

Method: 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.

Conclusion: 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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Antihypertensive Agents / administration & dosage*
  • Bosentan
  • Double-Blind Method
  • Female
  • Heart Failure, Systolic / complications*
  • Heart Failure, Systolic / diagnostic imaging
  • Heart Failure, Systolic / drug therapy*
  • Humans
  • Hypertension, Pulmonary / complications*
  • Hypertension, Pulmonary / drug therapy
  • Male
  • Severity of Illness Index
  • Sulfonamides / administration & dosage*
  • Treatment Outcome
  • Ultrasonography
  • Ventricular Dysfunction, Left / drug therapy


  • Antihypertensive Agents
  • Sulfonamides
  • Bosentan