LONG TERM EFFECTS OF TICLOPIDINE ON FIBRINOGEN AND HAEMORHEOLOGY IN PATIENTS WITH PERIPHERAL ARTERIAL DISEASES

Fibrinogen (Fgn) and haemorheologic parameters were serially measured in 44 pts (38 males, age 59+/−7) with claudicatio intermittens due to peripheral arterial obliterative disease (PAOD) treated for 24 months with Ticlopidine (T group, 250 mg b.i.d. p.os), or placebo (P group), in a double blind randomized controlled study, part of a larger clinical trial. Fgn (immunodiffusion), haematocrit (Ht, micromethod), whole blood viscosity (BV, Contraves LS 30, at 37 C) at high (94.5) and low (0.2 sec-1) shear rates (s.r.) and plasma viscosity (PV, Contraves LS 30) were measured three-monthly. The data were evaluated by means of ANOVA and Student's t test. The values in groups T and P did not differ at baseline except for greater BV at high s.r. in group P (p< 0.05). During the observation period circannual variations appeared especially in group T, where summer-time values for most parameters (Fgn, Ht, PV, low s.r. BV) were lower (significance from p<0.05 to <0.01) than the correspondent winter-time values, while a similar pattern was observed in group P only for PV (p<0.01). Fgn (p<0.05), Ht (p<0.01), and low s.r. BV (p<0.001) were significantly lowered in group T versus group P but only in the summer months (after about 1 year of treatment). In conclusion, this study proves that long-term Ticlopidine treatment in PAOD is associated with significant lowering of fibrinogen and “improvement” in haemoreologic tests although limited to the summer observations. Ticlopidine while positively interfering with haemorheology in PAOD may not counteract other mechanisms of rheologic deterioration probably occurring during winter. Long-term evaluation of drug effects should therefore take into account spontaneous or drug-enhanced seasonal changes of the investigated values.