Bosentan improves exercise tolerance and Tei index in patients with pulmonary hypertension and prostanoid therapy

Chest. 2005 Aug;128(2):709-13. doi: 10.1378/chest.128.2.709.


Study objective: Pulmonary arterial hypertension (PAH) is a progressive disease with a bad prognosis. Prostanoids are well established in the medical treatment of this disease. Treatment of patients with progressive disease despite prostanoids remains a therapeutic challenge. In this study, we examined the effect of adding bosentan, an endothelin antagonist, to existing prostanoid therapy on exercise capacity (6-min walking distance [6MWD]) and right ventricular (RV) function (Tei index) in patients with progressive pulmonary hypertension.

Design: Prospective, nonrandomized, open-label study.

Setting: University hospital.

Patients: Sixteen patients with pulmonary hypertension (PAH, n = 10; pulmonary hypertension due to other cause, n = 6) with progressive disease receiving either beraprost (n = 3), inhaled iloprost (n = 10), or iloprost IV (n = 3).

Interventions: Combination therapy with bosentan (final dosage, 125 mg bid) was initiated following an interval of 3-months minimum of unchanged prostanoid therapy.

Measurements and results: Tei index, 6MWD, and New York Heart Association (NYHA) functional class were assessed prior to the initiation of combination therapy (baseline), at 6 months after initiation of combination therapy, and every 3 months thereafter. Two patients were followed up for 6 months only; all remaining patients reached a mean follow-up period (+/- SD) of 13.5 +/- 5.0 months (range, 9 to 22 months). 6MWD increased by 42.5 +/- 66 m at 6 months and 44.6 +/- 66 m at the last follow-up (both time points vs baseline, p < 0.001), and Tei index improved by -0.13 +/- 0.08 at 6 months and - 0.13 +/- 0.11 at the last follow-up (both time points vs baseline, p < 0.001). All patients reported subjective improvements. Nine of 16 patients exhibited improvement in NYHA functional class at 6 months. No side effects occurred that required dose adjustment or discontinuation of the study medication.

Conclusion: Bosentan administered to patients with progressive pulmonary hypertension receiving prostanoids resulted in an increased exercise capacity and an improved RV function. Bosentan therefore appears to be well suited for combination therapy with prostanoids in selected patients pending results of ongoing randomized trials.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Antihypertensive Agents / therapeutic use*
  • Bosentan
  • Epoprostenol / analogs & derivatives*
  • Epoprostenol / therapeutic use
  • Exercise Tolerance / drug effects*
  • Female
  • Humans
  • Hypertension, Pulmonary / diagnostic imaging*
  • Hypertension, Pulmonary / drug therapy*
  • Iloprost / therapeutic use*
  • Male
  • Middle Aged
  • Prospective Studies
  • Prostaglandins / therapeutic use*
  • Sulfonamides / therapeutic use*
  • Ultrasonography
  • Vasodilator Agents / therapeutic use*


  • Antihypertensive Agents
  • Prostaglandins
  • Sulfonamides
  • Vasodilator Agents
  • beraprost
  • Epoprostenol
  • Iloprost
  • Bosentan