PMID- 16919008
OWN - NLM
STAT- MEDLINE
DCOM- 20070222
LR  - 20181201
IS  - 0014-2972 (Print)
IS  - 0014-2972 (Linking)
VI  - 36 Suppl 3
DP  - 2006 Sep
TI  - First experience with an oral combination therapy using bosentan and sildenafil 
      for pulmonary arterial hypertension.
PG  - 32-8
AB  - BACKGROUND: New oral substances such as beraprost, bosentan and sildenafil have 
      proven effective in different forms of pulmonary arterial hypertension (PAH), 
      both alone and in combination with standard treatment such as intravenous and 
      inhaled prostacyclins. However, there are few reports so far on the effect of a 
      combination of exclusively oral substances. In this paper, we present our initial 
      findings of treatment using a combination of these oral substances in a 
      heterogeneous group of patients with different forms of PAH. MATERIALS AND 
      METHODS: Eleven patients with a median age of 12.9 years (5.5-54.7 years) with 
      both idiopathic PAH and forms associated with congenital cardiac defects 
      (PAH-CHD) with a mean pulmonary arterial pressure > 25 mmHg were enrolled in an 
      observational, open-label, prospective, single-centre study. Either combination 
      treatment with bosentan and sildenafil was started initially, or an existing 
      bosentan treatment was complemented with sildenafil given as an add-on therapy. 
      Mean doses given were 2.3 +/- 0.6 mg kg(-1) for bosentan and 2.1 +/- 0.9 mg 
      kg(-1) for sildenafil. Clinical status, exercise capacity, and haemodynamics were 
      assessed at baseline and at the end of the observation period after a mean 
      follow-up time of 1.1 years (0.5-2.5 years). RESULTS: No major side effects 
      regarding liver function and blood pressure regulation were noted. One patient 
      died of sudden death elsewhere. Most patients were in New York Heart Association 
      (NYHA) functional class III. Clinical improvement was about one NYHA class (mean 
      2.8 +/- 0.4-1.6 +/- 0.8, P = 0.001), which was associated with an increase of 
      transcutaneous oxygen saturation (89.9 +/- 9.9-92.3 +/- 7.1%; P = 0.037), maximum 
      oxygen uptake (18.1 +/- 6.8-22.8 +/- 10.4 mL kg(-1) x min; P = 0.043), and 
      6-minute walking distance (351 +/- 58-451 +/- 119 m; P = 0.039). Mean pulmonary 
      arterial pressure measured invasively decreased (62 +/- 12-46 +/- 18 mmHg; P = 
      0.041). CONCLUSIONS: In our patient group, a combination of oral bosentan and 
      sildenafil proved to be safe and effective. Clearly, randomized, double-blind, 
      placebo-controlled studies are warranted to define the role and type of 
      combination therapies in PAH.
FAU - Lunze, K
AU  - Lunze K
AD  - Klinik fur angeborene Herzfehler/Kinderkardiologie, Deutsches Herzzentrum Berlin, 
      Berlin, Germany.
FAU - Gilbert, N
AU  - Gilbert N
FAU - Mebus, S
AU  - Mebus S
FAU - Miera, O
AU  - Miera O
FAU - Fehske, W
AU  - Fehske W
FAU - Uhlemann, F
AU  - Uhlemann F
FAU - Muhler, E G
AU  - Muhler EG
FAU - Ewert, P
AU  - Ewert P
FAU - Lange, P E
AU  - Lange PE
FAU - Berger, F
AU  - Berger F
FAU - Schulze-Neick, I
AU  - Schulze-Neick I
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Eur J Clin Invest
JT  - European journal of clinical investigation
JID - 0245331
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Endothelin Receptor Antagonists)
RN  - 0 (Phosphodiesterase Inhibitors)
RN  - 0 (Piperazines)
RN  - 0 (Purines)
RN  - 0 (Sulfonamides)
RN  - 0 (Sulfones)
RN  - BW9B0ZE037 (Sildenafil Citrate)
RN  - Q326023R30 (Bosentan)
SB  - IM
MH  - Administration, Oral
MH  - Adolescent
MH  - Adult
MH  - Antihypertensive Agents/*administration & dosage
MH  - Bosentan
MH  - Child
MH  - Child, Preschool
MH  - Drug Therapy, Combination
MH  - Endothelin Receptor Antagonists
MH  - Exercise Test/methods
MH  - Heart Defects, Congenital/complications/physiopathology
MH  - Humans
MH  - Hypertension, Pulmonary/complications/*drug therapy/physiopathology
MH  - Middle Aged
MH  - Phosphodiesterase Inhibitors/*administration & dosage
MH  - Piperazines/*administration & dosage
MH  - Prospective Studies
MH  - Purines
MH  - Sildenafil Citrate
MH  - Sulfonamides/*administration & dosage
MH  - Sulfones
MH  - Treatment Outcome
EDAT- 2006/08/22 09:00
MHDA- 2007/02/23 09:00
CRDT- 2006/08/22 09:00
PHST- 2006/08/22 09:00 [pubmed]
PHST- 2007/02/23 09:00 [medline]
PHST- 2006/08/22 09:00 [entrez]
AID - ECI1692 [pii]
AID - 10.1111/j.1365-2362.2006.01692.x [doi]
PST - ppublish
SO  - Eur J Clin Invest. 2006 Sep;36 Suppl 3:32-8. doi: 
      10.1111/j.1365-2362.2006.01692.x.