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

Objectives: Iloprost, an analogue of prostacyclin, is often utilised in sub jects with diabetes mellitus complicated by macroangiopathy. Methods: The effects of iloprost infusion on plasminogen activator inhibito r type-1 (PAI-1), glucometabolic control and cardiovascular equilibrium in patients with type-2 diabetes mellitus and peripheral arterial occlusive di sease were investigated. Thirteen (7 men/6 women) normal-weight, normotensi ve and non-smoker type-2 diabetic patients (63.8 +/- 3.4 years, mean +/- SD ) with peripheral arterial occlusive disease, stage-II according to Fontain e classification, were enrolled. Eight (four men/four women) patients under went three study designs, each separated by a 1-week interval: study I, inf usion of iloprost (3 ng kg(-1) min(-1) for 5 h) for 1 day alone (short-term treatment); study II, infusion of saline (for 5 h) for 1 day (control trea tment); study III, infusion of iloprost (3 ng kg(-1) min(-1) for 5 h) over a period of 28 days (long-term treatment). The remaining five (three men/tw o 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 fibrinogen, blood pressure and heart rate were determined i n all studies, while plasma insulin levels, blood HbA(1c), walking distance and Winsor index only in studies III and IV. Results: Both short- and long-term treatments with iloprost significantly r educed 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, respec tively). Long-term treatment with iloprost significantly increased walking distance (baseline vs end: 325 +/- 41 m vs 496 +/- 52 m, P < 0.0001), but n ot Winsor index. Neither glucometabolic control nor cardiovascular equilibr ium were affected by short- and long-term treatments with iloprost. Control and placebo treatments did not cause any significant modifications in the parameters evaluated. Conclusion: If confirmed by further investigations, the results of this pil ot study suggest that iloprost, infused for both brief and long periods, is able to reduce the cardiovascular risk factor PAI-1, increases free walkin g capacity and does not affect glucometabolic control and blood pressure in type-2 diabetic patients complicated by macroangiopathy.