Pulmonary Artery Remodelling With Bosentan

Exclusion Criteria1

• PAH other than iPAH or PAH-SScSignificant vasoreactivity during right heart catheterization defined as a fall in mPAP to < 40 mmHg with a decrease = 10 mmHg and with a normal cardiac index (= 2.5 l/min.m2)Severe obstructive lung disease: Forced Expiratory Volume in 1 second (FEV1)/ Forced Vital Vapacity (FVC) < 0.5Severe restrictive lung disease: Total Lung Capacity (TLC) < 0.7 of normal predicted valueHemoglobin <75% of the lower limit of the normal rangeSystolic blood pressure < 85 mmHgBody weight < 40 kgPregnancy or breast-feedingModerate to severe hepatic impairment, i.e., Child-Pugh Class B or C.Baseline aminotransferases, i.e., aspartate aminotransferases (AST) and/or alanine aminotransferases (ALT) > 3 times the upper limit of the normal (ULN) range.Treatment for iPAH or PAH-SSc within 1 month before start of study treatment, excluding warfarin and acute administration of vasodilators for vascular reactivity testing during heart catheterization.Treatment with epoprostenol or other prostacyclin analogs for iPAH or PAH-SSc within 1 month before start of study treatmentTreatment with glibenclamide (glyburide), fluconazole ketoconazole or ritonavir within 1 week before start of study treatment.Current treatment with cyclosporine A or tacrolimusHypersensitivity to bosentan or any of the excipients of its formulation.Patient who received an investigational drug (such as sildenafil) within 3 months before start of study treatmentConditions that prevent compliance with the protocol or adherence to therapy.