Trials of inhaled iloprost and other new vasodilating prostaglandins.

Pulmonary hypertension in its many different forms [1] was considered untreatable until the 1990s. With the exception of pulmonary hypertension associated with hypoxic lung disease, where long-term oxygen therapy (LTOT) improves survival in those patients with respiratory failure [2], the various forms of the disease often progress rapidly and lead to premature death. Work carried out in the early 1980s suggested that long-term, continuous intravenous prostacyclin might increase survival in severe primary pulmonary hyper-tension (PPH) [3, 4]. However, these papers reported unrandomized studies. This was also true of a report that showed that long-term anticoagulation improved survival in PPH and chronic thrombo-embolic pulmonary hypertension [5]. Although these ®ndings were encouraging, it remained unusual for PPH patients to receive these therapies. A randomized, controlled trial was undertaken in the USA, comparing long-term prostacyclin therapy plus conventional therapy, with conventional therapy alone, and was a landmark in the study of PPH. It not only applied strict entry criteria for PPH patients in the New York Heart Association (NYHA) grade III and IV, but was suf®ciently "powered" to test whether the treated group might demonstrate improved exercise tolerance as measured by the six-minute walk test. Quality of life was measured using the Nottingham Health pro®le questionnaire. Indeed, the prostacyclin treated patients demonstrated better exercise tolerance and enhanced quality of life after 3 months [6]. Surprisingly, and perhaps fortuitously, survival was also improved in the treated group at 3 months. This study has de®ned how future studies should be undertaken in pulmonary hypertension. It also led to the Food and Drug Administration issuing a license for prostacyclin in the treatment of PPH in the USA. Approval was also subsequently granted in France, Canada, Austria, Italy, and Holland. Indeed, for patients with isolated pulmonary arterial hypertension and scleroderma, a further randomized, controlled study of prostacyclin demonstrated improved quality of life [7]. As a result, prostacyclin can be considered an effective treatment, superior to lung transplantation in enhancing quality of life and improving survival. In addition to intravenous prostacyclin, its analogues, such as oral Beraprost (Toray Industries Inc., Japan) [8] and inhaled Iloprost (Schering AG, Germany) [9] have also been demonstrated to be effective in uncontrolled studies. Encouraged by these, large-scale, randomized, controlled studies are presently being undertaken and are to be applauded. A similar large-scale, randomized, controlled study has recently been completed for another subcutaneously delivered prostacyclin analogue, Uniprost (United Therapeutics Corporation, USA). The negative …