Intravenous iloprost for pulmonary arterial hypertension: still waiting for evidence

Irrespective of its aetiology, pulmonary arterial hypertension (PAH) is a serious disorder that results in right ventricular dysfunction, functional impairment and, ultimately, right heart failure and death. Over the last 20 yrs, significant advances in our understanding of the disease have led to the development of new, specific treatments. In 1996, a placebo-controlled trial demonstrated significant survival benefit with intravenous epoprostenol in severe idiopathic PAH 1. Observational studies also suggested epoprostenol was associated with improved long-term outcomes 2, 3. Subcutaneous treprostinil was subsequently shown to improve exercise capacity in PAH 4. More recently, i.v. treprostinil was approved for use by the US Food and Drug Administration in cases of intolerable subcutaneous infusion site pain based on a bioequivalence study 5 and prospective open-label trials 6, 7. Finally, randomised placebo-controlled trials documented the efficacy of inhaled iloprost either as monotherapy 8, or in addition to bosentan 9. These drugs are now part of the recommended treatment algorithm for PAH 10, together with endothelin receptor antagonists and phosphodiesterase type-5 inhibitors. Conversely, data on clinical efficacy of i.v. iloprost in PAH have been scarce. Iloprost is a stable synthetic analogue of prostacyclin 11. It possesses several pharmacological advantages over epoprostenol including enhanced chemical stability at room temperature and increased half-life, resulting in less frequent reservoir changes and the potential to avoid life-threatening events in case of sudden infusion interruption. Short-term open-label 12 and observational 13 studies suggested i.v. iloprost was effective in improving exercise capacity and pulmonary haemodynamics in PAH. However, these studies were limited in …