Compelling evidence of long-term outcomes in pulmonary arterial hypertension? A clinical perspective.

Pulmonary arterial hypertension (PAH) is a rare and progressive disease of the pulmonary arterial circulation that is characterized by a progressive rise in pulmonary vascular resistance, eventually leading to right-heart failure and death. There are currently 3 classes of drugs approved for the treatment of PAH: prostacyclin analogues, endothelin receptor antagonists, and phosphodiesterase type 5 inhibitors. All of these therapies have been approved for use on the basis of relatively small, short-term studies, yet it is common for each to be administered (alone or in combination) over the lifetime of a patient with PAH. Very few prospective, well-controlled PAH studies have examined long-term clinical outcomes associated with current medical therapy. Therefore, data that support the long-term therapeutic benefits of these long-term PAH therapies are limited and derived primarily from uncontrolled, observational studies. In this perspective, the authors review the published research to assess the strengths and weaknesses of the data that support the long-term clinical benefit of current PAH therapies. The authors conclude that current medical therapies approved for the treatment of PAH can provide sustained benefits in hemodynamic function and exercise capacity. The cumulative evidence, in the form of meta-analysis and registry data, suggest that patients are living longer compared with untreated patients; the reasons are likely multifactorial. Although definitive evidence will require randomized and properly controlled long-term trials, the current evidence supports the long-term use of these drugs for the treatment of patients with PAH.