Short- and long-term treatments with iloprost in diabetic patients with peripheral vascular disease: effects on the cardiovascular risk factor plasminogen activator inhibitor type-1

Abstract Objectives: Iloprost, an analogue of prostacy- clin, is often utilised in subjects with diabetes mellitus complicated by macroangiopathy. Methods: The eects of iloprost infusion on plasminogen activator inhibitor type-1 (PAI-1), glucometabolic con- trol and cardiovascular equilibrium in patients with type-2 diabetes mellitus and peripheral arterial occlusive disease were investigated. Thirteen (7 men/6 women) normal-weight, normotensive and non-smoker type-2 diabetic patients (63.8 3.4 years, mean SD) with peripheral arterial occlusive disease, stage-II according to Fontaine classi®cation, were enrolled. Eight (four men/four women) patients underwent three study de- signs, each separated by a 1-week interval: study I, in- fusion of iloprost (3 ng kgA1 minA1 for 5 h) for 1 day alone (short-term treatment); study II, infusion of saline (for 5 h) for 1 day (control treatment); study III, infu- sion of iloprost (3 ng kgA1 minA1 for 5 h) over a period of 28 days (long-term treatment). The remaining ®ve (three men/two women) patients underwent study IV only, infusion of saline over a period of 28 days (placebo treatment). Plasma levels of glucose, plasminogen, PAI-1 activity and ®brinogen, blood pressure and heart rate were determined in all studies, while plasma insulin levels, blood HbA1c, walking distance and Winsor index only in studies III and IV. Results: Both short- and long-term treatments with ilo- prost signi®cantly reduced PAI-1 activity (baseline vs end: 17.4 1.9 AU/ml vs 15.0 1.6 AU/ml, P < 0.02; 20.5 7.6 AU/ml vs 7.9 2.1 AU/ml, P < 0.002,respectively). Long-term treatment with iloprost signi®- cantly increased walking distance (baseline vs end: 32541m vs 49652m, P<0.0001), but not Winsor index. Neither glucometabolic control nor car- diovascular equilibrium were aected by short- and long-term treatments with iloprost. Control and placebo treatments did not cause any signi®cant modi®cations in the parameters evaluated. Conclusion: If con®rmed by further investigations, the results of this pilot study suggest that iloprost, infused for both brief and long periods, is able to reduce the cardiovascular risk factor PAI-1, increases free walking capacity and does not aect glucometabolic control and blood pressure in type-2 diabetic patients complicated by macroangiopathy.