Prostanoids have played a prominent role in the treatment of
pulmonary arterial hypertension (PAH). Several compounds and methods of administration have been studied: chronic intravenously infused
epoprostenol, chronic subcutaneously infused
treprostinil, inhaled
iloprost, and oral
beraprost. Chronic intravenous
epoprostenol therapy has had a substantial impact on the clinical management of patients with severe PAH. It improves exercise capacity, hemodynamics, and survival in patients with
idiopathic pulmonary arterial hypertension (IPAH). It also improves exercise capacity and hemodynamics in patients with PAH occurring in association with scleroderma. The complexity of
epoprostenol therapy (chronic
indwelling catheters, reconstitution of the drug, operation of the
infusion pump, and others) has led to attempts to develop other
prostanoids with simpler modes of delivery.
Treprostinil, a stable
prostacyclin analogue with a half-life of 3 h, has been developed for subcutaneous delivery. It has beneficial effects on exercise and hemodynamics, which depend somewhat on the dose achieved. This, in turn, is determined by the patient's ability to tolerate the drug's side effects, including
pain and
erythema at the infusion site. Inhaled
iloprost therapy may provide selectivity of the hemodynamic effects to the lung vasculature, thus avoiding systemic side effects. In a randomized and controlled trial,
iloprost resulted in improvement in a combined end point incorporating the New York Heart Association functional class, 6-min walk test, and deterioration or death.
Beraprost is the first orally active
prostacyclin analogue. In the first of two randomized controlled trials,
beraprost increased exercise capacity in patients with IPAH, with no significant changes in subjects with associated conditions. Hemodynamics did not change significantly, and no difference in survival was detected between the two treatment groups. The second study showed that
beraprost-treated patients had less
disease progression at six months and confirmed the results of the previous trial. However, this improvement was no longer present at 9 or 12 months. In conclusion, though treatment with
prostanoids is complicated by their generally short half-lives and complicated drug delivery systems, they continue to play an important role in the treatment of PAH.