Sitaxsentan for Treatment of Pulmonary Hypertension

Pulmonary arterial hypertension (PAH)is defined by persistently elevated pressures in the pulmonary vasculature as evidenced by mean pulmonary artery pressure greater than 25 mm Hg at rest or greater than 30 mm Hg during exercise.1 If an associated cause for PAH is identi-fied, it may be managed by treatment of the causative factor. Idiopathic PAH (IPAH) has no known cause and has been referred to in past practice as pri-mary pulmonary hypertension.2 Much of the focus of therapeutic investigations in PAH has involved patients with IPAH due to their limited survival time after di-agnosis (usually not exceeding 3–5 y). Current pharmacotherapy of PAH in-cludes vasoactive drugs such as calcium-channel blockers (nifedipine and dilti-azem), prostaglandin analogs (epopros-tenol, iloprost, and treprostinil), endothelin (ET) receptor antagonists (bosentan), and phosphodiesterase inhibitors (silden-afil). Drugs may be combined in patients whose disease is refractory to single agents. Surgical interventions such as balloon atrial septostomy or lung trans-plantation are reserved for patients whose PAH does not respond to combination pharmacotherapy. Right heart failure may arise from excess right ventricular afterload in the pulmonary system dur-ing PAH. Symptomatic patients may be treated for venous congestion with di-uretics and inotropes such as digoxin, and hypoxia is treat-ed with supplemental oxygen. Altered pulmonary micro-circulation and venous stasis predispose patients with IPAH to an increased risk of pulmonary embolism. Chron-ic anticoagulation is recommended for these patients since prolonged survival has been documented in this group when warfarin therapy was given.