title: Addition of sildenafil in patients with pulmonary arterial hypertension with inadequate response to bosentan monotherapy.
abstract: BACKGROUND
  Pulmonary arterial hypertension (PAH) remains a progressive disease despite improvement when using one of three medication classes: prostanoids, endothelin receptor antagonists or phosphodiesterase-5 inhibitors. Combination therapy has been proposed for patients with unsatisfactory response to monotherapy.
  
  
  OBJECTIVE
  To examine the effect of adding sildenafil to bosentan on 6 min walk distance (6MWD) and New York Heart Association (NYHA) classification in patients with PAH who achieved inadequate improvement with bosentan monotherapy.
  
  
  METHODS
  Patients with idiopathic PAH or connective tissue disease-associated PAH, and who had either self-reported inadequate improvement in exercise tolerance or a decline in 6MWD after initial improvement, were included in the study (n=10). Data on 6MWD and NYHA class at baseline (before initiation of bosentan), three and six months after baseline, second baseline (before initiation of combination therapy with sildenafil), and three and six months after second baseline were analyzed for any changes.
  
  
  RESULTS
  Mean time from initiation of bosentan monotherapy to initiation of combination therapy was 558 days (range 150 to 900 days). Six months after initiation of bosentan, 6MWD increased by 57.2 m above the baseline of 314.4 m. Six months after combination therapy, 6MWD was 62.80 m higher than the baseline before initiation of combination therapy of 339 m (P<0.02). The overall increase in 6MWD six months after combination therapy was higher than the first baseline by 87.4 m (P not significant). NYHA functional class did not improve with combination therapy in all patients.
  
  
  CONCLUSIONS
  Initiating combination therapy in patients who achieve an inadequate improvement in exercise tolerance with monotherapy may result in further improvement in exercise tolerance.
authors.affiliation: University of Manitoba, Winnipeg, Canada. umporho0@cc.umanitoba.ca
authors.forename: Nancy R
authors.initials: NR
authors.lastname: Porhownik
authors.forename: Hassan
authors.initials: H
authors.lastname: Al-Sharif
authors.forename: Zoheir
authors.initials: Z
authors.lastname: Bshouty
mesh_terms: D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D000077300:Bosentan; D004359:Drug Therapy, Combination; D017079:Exercise Tolerance; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage*; D010879:Piperazines / Q000008:administration & dosage*; D011687:Purines / Q000008:administration & dosage; D000068677:Sildenafil Citrate; D013449:Sulfonamides / Q000008:administration & dosage*; D013450:Sulfones / Q000008:administration & dosage*; D017211:Treatment Failure; D055815:Young Adult
chemical_list: D000959:Antihypertensive Agents; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013449:Sulfonamides; D013450:Sulfones; D000068677:Sildenafil Citrate; D000077300:Bosentan