Combination Pharmacotherapy in the Treatment of Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a disorder of the small pulmonary arteries characterized by progressive fibrotic and proliferative changes that result in an increased pulmonary vascular resistance. It is a progressive and debilitating disease that leads to right ventricular dysfunction, impairment in activity tolerance and eventually right-sided heart failure, and premature death. The treatment goals for PAH include improvement in symptoms, improvement in functional class and exercise class, decreased morbidity, and preventing mortality. Combination therapy in the treatment of PAH is an emerging therapeutic option. Combining therapies with differing mechanisms of action will maximize therapeutic benefits such as symptom control and increased rate of survival. The updated 2007 American College of Chest Physicians evidence-based clinical practice guidelines recommend combination therapy in functional classes III and IV if there is no improvement with current therapy or if there is deterioration in class. PAH monotherapy has been shown to improve symptoms, but the patients' hemodynamic parameters may not be normalized, leading to further pulmonary vascular remodeling. Combination therapy offers an additional option for those patients who are unable to stabilize on monotherapy.