Outpatient treatment of severe peripheral ischemia with intravenous intermittent low-dose iloprost. An open pilot study.

BACKGROUND

Iloprost given in a standard dose regimen (0.5-2 ng/kg/min for 6 hours daily over 21-28 days) has proven to be effective and safe in hospitalized patients with critical limb ischemia. Major drawbacks of the standard regimen are the high frequency of side effects, the long duration of the daily infusion, and a hospital stay of 3 to 4 weeks. Recently, the efficacy of low doses of iloprost (25 mg/day) was demonstrated. This open pilot study was undertaken to identify a more practical and cost-effective regimen with less side effects. The feasibility, efficacy and safety of an individually adapted, intermittently applied low-dose iloprost regimen in an outpatient setting were evaluated.

METHODS

Twenty-seven patients with severe peripheral ischemia in the limbs or part of the limb due to various etiologies, who were eligible for outpatient treatment, were enrolled into the study. The infusion of iloprost (50 microg in 250 ml 0.9% saline) was started at 0.5 ng/kg BW/min and titrated to the individual optimum dose, which was defined as the maximum dose at which the patient felt entirely comfortable. The frequency of the iloprost infusions and the duration of the treatment were individually determined in each patient according to the severity of the clinical condition. Outcome endpoints were the response rates achieved by day 28, defined as substantial relief from rest pain and evidence of ulcer healing. The patients were followed up for a minimum of 6 months.

RESULTS

A total of 27 patients (15 male, 12 female, mean age 65 years) were treated. Twenty-four patients received daily infusions with a break at weekends (5 times/week); 3 patients were treated every second day (3 times a week). The mean daily iloprost dose actually given was 20+/-5 microg, the mean duration of treatment was 3.6+/-0.8 weeks, i.e. a mean of 17+/-4 infusions were administered. Six patients with one-vessel run-off underwent percutaneous transluminal angioplasty (PTA) of their single calf vessel. Twenty-six patients showed clinical improvement by day 28; excluding those who had had PTA, the response rate to iloprost was 74% (20/27). No patient required admission to hospital while receiving outpatient treatment; no side effects occurred after adjustment to the optimum dose. At long-term follow-up (11+/-3 months), 76% of patients were alive and had a viable limb.

CONCLUSIONS

In a limited number of patients with severe peripheral ischemia of various etiologies, long-term outpatient treatment with an individually adapted low-dose iloprost regimen was feasible and safe. Our data suggest that flexible treatment modalities might be as effective as rigid standard treatment regimens, the former being more advantageous in terms of greater practicability and cost-effectiveness due to outpatient management. Further studies are needed to confirm the efficacy of this individually adapted, low-dose outpatient iloprost treatment regimen in a larger number of patients.