title: Sildenafil add-on therapy in paediatric pulmonary arterial hypertension, experiences of a national referral centre.
abstract: OBJECTIVE
  In paediatric pulmonary arterial hypertension (PAH), the effectiveness of add-on combination PAH-therapy has not yet been systematically studied. The purpose of this study was to determine the effect of sildenafil add-on therapy in paediatric PAH patients treated with bosentan.
  
  
  METHODS
  In this observational study within a national paediatric patient cohort, follow-up data of 24 consecutive paediatric PAH patients initially treated with bosentan monotherapy and prospectively followed at the Dutch national referral centre for paediatric PAH in 2007-2013, were reviewed. Patients received add-on sildenafil therapy in case of clinical worsening.
  
  
  RESULTS
  Fifteen children received add-on sildenafil therapy; nine remained on bosentan monotherapy. Patient characteristics, 6-minute walk distance (6MWD), WHO functional class (WHO-FC), N-terminal pro-Brain Natriuretic Peptide (NT-proBNP), and haemodynamic measurements at bosentan start were similar in both patient groups. In children with clinical worsening, sildenafil add-on therapy improved 6MWD at 5, 10, 15 and 21 months of follow-up, improved WHO-FC at 10, 15 and 21 months and stabilised NT-proBNP. Patients who received add-on sildenafil therapy had more advanced disease progression during bosentan monotherapy. Despite that, they had better or, at least, no worse survival compared to patients who remained on bosentan monotherapy.
  
  
  CONCLUSIONS
  In children with PAH, sildenafil add-on therapy indicated by clinical deterioration on bosentan monotherapy, was associated with a significant improvement of WHO-functional class and 6MWD. Despite clinical deterioration on bosentan monotherapy, patients receiving sildenafil add-on therapy, had either better or, at least, no worse survival than patients remaining on bosentan monotherapy.
authors.affiliation: Department of Paediatric Cardiology, Centre for Congenital Heart Diseases, Beatrix Children's Hospital, University Medical Centre Groningen, , Groningen, The Netherlands.
authors.forename: Johannes M
authors.initials: JM
authors.lastname: Douwes
authors.forename: Marcus T R
authors.initials: MT
authors.lastname: Roofthooft
authors.forename: Rosa L E
authors.initials: RL
authors.lastname: Van Loon
authors.forename: Mark-Jan
authors.initials: MJ
authors.lastname: Ploegstra
authors.forename: Beatrijs
authors.initials: B
authors.lastname: Bartelds
authors.forename: Hans L
authors.initials: HL
authors.lastname: Hillege
authors.forename: Rolf M F
authors.initials: RM
authors.lastname: Berger
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D000077300:Bosentan; D002648:Child; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D065627:Familial Primary Pulmonary Hypertension; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D009426:Netherlands; D010879:Piperazines / Q000008:administration & dosage*; D011687:Purines / Q000008:administration & dosage; D063728:Secondary Care Centers; D000068677:Sildenafil Citrate; D013449:Sulfonamides / Q000008:administration & dosage*; D013450:Sulfones / Q000008:administration & dosage*; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage*
chemical_list: D000959:Antihypertensive Agents; D010879:Piperazines; D011687:Purines; D013449:Sulfonamides; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate; D000077300:Bosentan