Effects of long-term bosentan in children with pulmonary arterial hypertension

J Am Coll Cardiol. 2005 Aug 16;46(4):697-704. doi: 10.1016/j.jacc.2005.01.066.

Abstract

Objectives: This study investigated the long-term outcome of children with pulmonary arterial hypertension (PAH) treated with bosentan therapy, with or without concomitant prostanoid therapy.

Background: Bosentan, an oral endothelin ET(A)/ET(B) receptor antagonist, improves hemodynamics and exercise capacity in adults with PAH; however, limited data are available on its long-term effects in children.

Methods: In this retrospective study, 86 children with PAH (idiopathic, associated with congenital heart or connective tissue disease) started bosentan with or without concomitant intravenous epoprostenol or subcutaneous treprostinil therapy. Hemodynamics, World Health Organization (WHO) functional class, and safety data were collected.

Results: At the cutoff date, 68 patients (79%) were still treated with bosentan, 13 (15%) were discontinued, and 5 (6%) had died. Median exposure to bosentan was 14 months. In 90% of the patients (n = 78), WHO functional class improved (46%) or was unchanged (44%) with bosentan treatment. Mean pulmonary artery pressure and pulmonary vascular resistance decreased (64 +/- 3 mm Hg to 57 +/- 3 mm Hg, p = 0.005 and 20 +/- 2 U x m2 to 15 +/- 2 U x m2, p = 0.01, respectively; n = 49). Kaplan-Meier survival estimates at one and two years were 98% and 91%, respectively. The risk for worsening PAH was lower in patients in WHO functional class I/II at bosentan initiation than in patients in WHO class III/IV at bosentan initiation.

Conclusions: These data suggest that bosentan, an oral endothelin ET(A)/ET(B) receptor antagonist, with or without concomitant prostanoid therapy, is safe and efficacious for the treatment of PAH in children.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Antihypertensive Agents / adverse effects
  • Antihypertensive Agents / therapeutic use*
  • Bosentan
  • Child
  • Child, Preschool
  • Drug Therapy, Combination
  • Endothelin A Receptor Antagonists*
  • Endothelin B Receptor Antagonists*
  • Female
  • Humans
  • Hypertension, Pulmonary / drug therapy*
  • Hypertension, Pulmonary / mortality
  • Male
  • Prostaglandins / administration & dosage
  • Prostaglandins / therapeutic use
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Safety
  • Sulfonamides / adverse effects
  • Sulfonamides / therapeutic use*
  • Survival Analysis
  • Time
  • Treatment Outcome*

Substances

  • Antihypertensive Agents
  • Endothelin A Receptor Antagonists
  • Endothelin B Receptor Antagonists
  • Prostaglandins
  • Sulfonamides
  • Bosentan