PMID- 24390161
OWN - NLM
STAT- MEDLINE
DCOM- 20140326
LR  - 20181202
IS  - 1468-201X (Electronic)
IS  - 1355-6037 (Linking)
VI  - 100
IP  - 3
DP  - 2014 Feb
TI  - Sildenafil add-on therapy in paediatric pulmonary arterial hypertension, 
      experiences of a national referral centre.
PG  - 224-30
LID - 10.1136/heartjnl-2013-304895 [doi]
AB  - 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.
FAU - Douwes, Johannes M
AU  - Douwes JM
AD  - Department of Paediatric Cardiology, Centre for Congenital Heart Diseases, 
      Beatrix Children's Hospital, University Medical Centre Groningen, , Groningen, 
      The Netherlands.
FAU - Roofthooft, Marcus T R
AU  - Roofthooft MT
FAU - Van Loon, Rosa L E
AU  - Van Loon RL
FAU - Ploegstra, Mark-Jan
AU  - Ploegstra MJ
FAU - Bartelds, Beatrijs
AU  - Bartelds B
FAU - Hillege, Hans L
AU  - Hillege HL
FAU - Berger, Rolf M F
AU  - Berger RM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Heart
JT  - Heart (British Cardiac Society)
JID - 9602087
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Piperazines)
RN  - 0 (Purines)
RN  - 0 (Sulfonamides)
RN  - 0 (Sulfones)
RN  - 0 (Vasodilator Agents)
RN  - BW9B0ZE037 (Sildenafil Citrate)
RN  - Q326023R30 (Bosentan)
SB  - IM
MH  - Adolescent
MH  - Age Factors
MH  - Antihypertensive Agents/*administration & dosage
MH  - Bosentan
MH  - Child
MH  - Cohort Studies
MH  - Drug Therapy, Combination
MH  - Familial Primary Pulmonary Hypertension
MH  - Female
MH  - Humans
MH  - Hypertension, Pulmonary/diagnosis/*drug therapy/mortality
MH  - Male
MH  - Netherlands
MH  - Piperazines/*administration & dosage
MH  - Purines/administration & dosage
MH  - Secondary Care Centers
MH  - Sildenafil Citrate
MH  - Sulfonamides/*administration & dosage
MH  - Sulfones/*administration & dosage
MH  - Treatment Outcome
MH  - Vasodilator Agents/*administration & dosage
EDAT- 2014/01/07 06:00
MHDA- 2014/03/29 06:00
CRDT- 2014/01/07 06:00
PHST- 2014/01/07 06:00 [entrez]
PHST- 2014/01/07 06:00 [pubmed]
PHST- 2014/03/29 06:00 [medline]
AID - heartjnl-2013-304895 [pii]
AID - 10.1136/heartjnl-2013-304895 [doi]
PST - ppublish
SO  - Heart. 2014 Feb;100(3):224-30. doi: 10.1136/heartjnl-2013-304895.