Combination therapy for the treatment of pulmonary arterial hypertension

Multiple medical therapies have been developed for the treatment of pulmonary arterial hypertension (PAH) over the last decade and a half. Unfortunately, none of these medications is curative and the majority of patients develop disease progression despite treatment. Presently available medications target one of three known pathways that have been implicated in disease pathogenesis. The multiplicity of pulmonary vascular abnormalities identified in PAH provides the rationale for a therapeutic strategy that targets more than one mechanism at a time. Although a handful of studies have demonstrated clinical improvement in PAH patients who have a second medication added to stable background therapy in a randomized, placebo-controlled fashion, it is unclear whether the derived benefit is due to the combination of two therapies or merely the response to the new agent. This review discusses the rationale for combination therapy, critically reviews the findings of presently completed combination studies and outlines the need for new studies that are better designed to determine whether combination therapy is more efficacious than single agent therapies for the treatment of PAH.