LOW-DOSE ILOPROST INFUSIONS COMPARED TO THE STANDARD-DOSE IN PATIENTSWITH PERIPHERAL ARTERIAL OCCLUSIVE DISEASE FONTAINE STAGE-IV

Background: Intravenous iloprost, titrated from 0.5 up to 2.0 ng/kg/mi n has been shown inpatients with PAOD III/IV to significantly improve healing of trophic lesions, relief of rest pain, and reduce the rate o f major amputation or death at 6 months as compared to placebo. The ef fect is considered related to improvement of the microcirculation. The aim of the present trial was to identify an optimum dose regarding tr eatment response and tolerability, by studying 4 doses of 25, 50, 75 a nd 100 mu g iloprost daily. Patients and Methods: 302 patients with PA OD IV were randomised via a double-blind fashion to one of the 4 doses . The primary endpoint was the responder rate at end of treatment. Res ponders were defined as patients with very good or good global efficac y, as judged by lesion healing and pain relief. Side effects were docu mented and a pre-defined benefit/risk index was calculated. Results: N o dose-dependency of iloprost regarding primary or secondary endpoints was observed. The rate of responders ranged between 48.7-53.5%. Side effects, mainly related to vasodilation, increased dose-dependently (p < 0.001, chi(2)-test), with a significant decrease of the benefit/ris k index from 2.19 +/- 1.19 to 1.64 +/- 0.97 (p = 0.012, ANOVA). Respon ders had a better outcome at 6 months than non-responders (2.6 fold hi gher rate of major amputation or death; life table analysis). Conclusi ons: It is concluded that iloprost should be titrated to the optimum r ather than maximum tolerated dose, since a higher incidence of side ef fects not associated with an increased treatment response was observed at higher doses.