Effects of defibrotide on physical performance and hemorheologic picture in patients with peripheral arteriopathy

In a random double-blind study versus placebo, 60 ambulatory patients with peripheral occlusive disease of the lower limbs and claudicatio intermittens (Leriche's stage 2), were treated for 60 days with defibrotide (400 mg b.i.d., oral, n = 30) or placebo (n = 30). Patients in the defibrotide group received additional treatment with the same drug at the reduced rate of 400 mg once daily for another 120 days for maintenance (total treatment duration 180 days). All patients were assessed at intake and 60 days for relative and absolute walking distance (RWD and AWD) in a standard treadmill test and for the Winsor Index (WI) at rest and after exercise; patients of the defibrotide treatment group were retested in the same way at 90-180 days. In a subgroup of patients (defibrotide = 11, placebo = 12), blood samples were obtained for the assessment of whole blood and plasma viscosity at intake and after 60 days of treatment. These samples could not be collected properly in the remaining cases, for technical reasons. At day 60, we compared the effects of the two treatments on physical performance: mean (SE) values of RWD were for defibrotide 148 (9.7) and 179 (12.4) m in basal and post-treatment conditions, respectively, and 209 (16.2) and 212 (17.1) m for placebo. Similar changes were observed for AWD: for defibrotide 206 (13.4) and 241 (15.2) m and for placebo 270 (22.9) and 272 (23.1) m. The mean changes were significantly larger with defibrotide: for RWD + 33 (7.1) vs. + 0.3 (3.8) m (p < 0.01) and for AWD + 34 (9.2) and -2 (6.6) m (p < 0.01). The overall gain of walking distance after maintenance therapy with the reduced defibrotide dosage amounted to approximately + 50% over basal (after 180 days). Blood and plasma viscosity improved in patients on defibrotide but the change fell short of statistical significance versus placebo. All findings confirm the potential usefulness of defibrotide in the treatment of peripheral arterial disease, at the same time encouraging further studies of the involved mechanisms of action.