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Pulmonary arterial hypertension (PAH) - a complex and progressive disease that carries significant morbidity and mortality despite optimal medical treatment. Combination therapy for PAH can be more effective than monotherapy. The present randomized trial compared the safety and efficacy of sildenafil ambrisentan combination therapy with sildenafil monotherapy. Twenty-two patients of Eisenmenger syndrome and five patients of idiopathic PAH were randomized to two arms. There was a significant improvement in NYHA functional class and mean pulmonary artery pressure, while an insignificant improving trend was observed for 6-min walk distance and oxygen saturation, following the 12 weeks of combination therapy. An upfront combination therapy was found to be safe and effective in the management of PAH patients.