Role of Combination Therapy in the Treatment of Pulmonary Arterial Hypertension

As a result of the multimechanistic pathology of pulmonary arterial hypertension (PAH), combination therapy is emerging as a potential treatment option. Recent guidelines from the American College of Chest Physicians and expert consensus from the American College of Cardiology Foundation and American Heart Association do not definitively support or disapprove of combination pharmacotherapy for the treatment of PAH. Published trials have investigated different combinations including endothelin receptor antagonists with prostanoids, prostanoids with phosphodiesterase inhibitors, and phosphodiesterase inhibitors with endothelin receptor antagonists. Pertinent trials on combination pharmacotherapy for PAH were identified through a MEDLINE search of literature from 1967–2009 in addition to a manual search of references from the articles retrieved. Search results identified 12 trials that evaluated combination therapy for PAH; some included an add‐on agent for patients who failed treatment with monotherapy and others were placebo controlled. Even with the published data, the overall consensus is unclear. Well‐designed, larger trials with validated end points are needed to further identify when to initiate combination therapy for the treatment of PAH. Meanwhile, perhaps the most appropriate situation for using combination pharmacotherapy may be in the setting of a lack of clinical improvement or deterioration.