Efficacy of a novel method of intravenous infusion of the prostaglandin analogue iloprost for the treatment of lower-limb critical ischemia: An open-label, nonrandomized study in two cohorts

Background: Patients with advanced peripheral atherosclerotic occlusive disease who are no longer candidates for either surgical or intravascular treatment or who have undergone unsuccessful surgical revascularization may be treated with IV prostanoids. Objective: The aim of this study was to assess the efficacy, tolerability, compliance, and cost of a new system of prostanoid administration that provides a constant plasma concentration of iloprost and maintains the efficacy of the drug while reducing the risk for adverse effects (AEs) and the overall cost of treatment compared with the actually adopted infusion system. Methods: This open-label, nonrandomized study was conducted at the University Hospital of Catania (Catania, Italy). Patients with chronic critical ischemia. who were not candidates for surgical revascularization were observed. The study population was divided into 2 groups: patients in group A were treated with a continuous 6-hour IV infusion of iloprost 0.5 to 2.0 ng/kg.min once daily for at least 14 consecutive days, and patients in group B were treated with a 20-day iloprost continuous IV infusion at a mean dosage of 25 mug/d by means of a portable elastomeric infusion system. Every 5 days the patient was admitted to the day-hospital setting to replenish the drug. Primary end points were rates of major and minor amputations and death; secondary end points were complete relief or a marked reduction of pain at rest, as reflected by discontinuation. of analgesic therapy and by a decrease in the patients' complaints of pain, as well as by the satisfactory healing of ulcerations. Tolerability, compliance, and cost also were assessed. Results: Fifty-six patients (34 men, 22 women; mean [SD] age, 67 [11] years) entered the study. Group A comprised 25 patients; group B, 31 patients. The rate of major amputation in patients at Fontaine stage IV was higher in group A (33.3%) compared with group B (20.0%). The death rate was higher in group A (4.0%) than in group B (3.2%). Pain at rest completely subsided in 37.5% of patients in group A and 68.8% of patients in group B. Trophic lesions healed in 44.4% and 73.3% of patients in groups A and B, respectively. In group A, 40.0% of patients experienced AEs (ie, hyperemia, headache, flushing) that required a reduction in dose. In group B, 6.5% of patients had hyperemia at the injection site that required a reduction in dose. Total cost was C8745.20 in group A, with a mean hospital stay of 20 days; total cost in group B was C1995.60, with a mean hospital stay of 6 days. Overall, patients' quality of life, assessed as the ability to resume their normal social activities, improved. Conclusions: In this study of patients with chronic lower-limb critical ischemia, due to the consistent blood level achieved with iloprost, 20-day iloprost continuous IV infusion at a mean dosage of 25 mug/d administered by means of a portable elastomeric infusion system was shown to be similarly or more effective than the methods used by the most important European trials (ie, iloprost 0.5-2.0 ng/kg.min once daily for at least 14 consecutive days). Furthermore, the patients were more compliant and the cost of treatment and the length of hospitalization were reduced compared with iloprost 0.5 to 2.0 ng/kg.min once daily for at least 14 consecutive days.