What is pulmonary arterial hypertension?

Pulmonary arterial hypertension (PAH) is a term that was coined in 1998 at the World Health Organization Symposium on Pulmonary Hypertension at Evian, France. Because a clinically useful classification for pulmonary hypertension was lacking, the late Alfred Fishman proposed a clinical classification system for pulmonary hypertension which has been widely adopted. Its purpose was to provide a guide to physicians who encounter a patient with pulmonary hypertension of uncertain etiology. The classification system helped direct the clinical evaluation of the patient so that underlying disease(s) that might be causing or contributing to the pulmonary hypertension could be identified. PAH (also known as Category 1) includes patients who have an elevation in pulmonary artery pressure with a normal pulmonary wedge pressure, either alone or in association with many other diseases. In 1995, intravenous epoprostenol became the first treatment approved by the FDA for PPH (now referred to as IPAH). [2] Subsequently, a second epoprostenol trial for patients with pulmonary hypertension associated with scleroderma resulted in FDA approval for that condition. [3] Both studies were initiated prior to the Evian classification system. In 2000, the FDA approved bosentan for pulmonary hypertension, but in this instance the FDA agreed to approve it for the entire category of pulmonary hypertension known as PAH (Category 1) and did not require separate clinical trials to evaluate its efficacy in patients with different associated diseases. The reason behind the FDA's decision to do this has not been disclosed. However, since then, all of the new therapies (prostacyclins, endothelin receptor blockers, and phosphodiesterase-5 inhibitors) that have been approved by the FDA to treat patients with pulmonary hypertension have been approved for the entire category of PAH. As a result, physicians are left with the perception that these therapies are safe and effective for patients with Category 1 PAH irrespective of the associated condition, and are neither safe nor effective for patients with pulmonary hypertension that fall into the other four categories. Whether or not this is true is unknown but it has wide implications for those patients whose pulmonary hypertension falls outside of Category 1. Implicit with the designation of PAH is the notion that the disease originates and/or is confined to the pulmonary arteriolar bed, and that these drugs in some way target that region of the pulmonary circulation. Yet there has never been a human clinical trial that has demonstrated the mechanism or site of action …