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.
