[Indirect comparison of changes of parameters of hemostasis during short-term use of ticlopidine and clopidogrel in patients with non-ST elevation acute coronary syndrome].

UNLABELLED

Effects of thienopyridines ticlopidine (TIC) and clopidogrel (CL) on hemostasis in patients (pts) with non-ST-elevation acute coronary syndromes (NSTEACS) have not been compared.

AIM

To compare changes of some markers of coagulation and platelet activation during short term use of TIC and CL in pts with NSTEACS.

METHODS

Aspirin treated pts with NSTEACS (<48 hours from pain onset, Braunwald class IIIb) were included into 2 consecutive studies: 37 pts receiving unfractionated heparin (UFH) were randomized to open TIC (n=19, 500 mg BID for 2 days and 250 mg BID for subsequent 5 days) or no TIC (n=18); 19 pts receiving enoxaparin were randomized to CL (n=10, 300 mg on day 1 and 75 mg/day for subsequent 6 days) or no CL (n=9). At baseline, on days 1, 3, 7 and 14 (7 days after thienopyridines discontinuation) we measured ADP-induced and spontaneous platelet aggregation (PA), levels of prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT), von Willebrand factor (vWF), fibrinogen, tissue type plasminogen activator antigen (tPA), plasminogen activator inhibitor activity (PAI) and D-dimer (Dd), and counted platelet number.

RESULTS

Maximal suppression of PA was obtained on 7-th and 3-rd days in TIC and CL groups, respectively. Compared with their controls TIC treated pts in 7 days after TIC discontinuation had lower levels of TAT (3.61 and 2.77 ng/ml, respectively, r<0.05) and fibrinogen (3.84 and 3.16 g/l, respectively, r<0.05). There were no significant differences between intervention and control groups in these parameters in study with CL. Level of vWF in TIC treated pts was lower than in controls on days 3 (163 and 186%, respectively, r<0.05) and 14 (144 and 173%, respectively, p<0.01). In CL treated pts vWF level was lower relative to controls on days 3 and 7 (152 and 185%, r<0.05, 141 and 166%, r<0.05, respectively). tPA levels in study with TIC did not differ between intervention and control groups. tPA in CL treated pts exceeded its level in controls on days 3, 7, and 14 (25.7 and 20.2 ng/ml, 26.5 and 12.9 ng/ml, 24.6 and 15.7 ng/ml, respectively). On the same days level of Dd in pts receiving CL was significantly higher than in control group (969 and 702 ng/ml, 970 and 575 ng/ml, 806 and 484 ng/ml on days 3, 7 and 14, respectively). Activity of PAI in TIC group was higher than in controls on day 7 (13.6 and 8.2 U/l, r<0.05), and at this moment level of Dd was lower in TIC treated patient (770 and 515 ng/ml in control and TIC groups, respectively, r<0.05). CL and control groups had similar PAI activity. Mean platelet volume rose relative to initial level and to control group only in CL treated patients (9.0 and 8.4 fl, 9.6 and 8.4 fl, 9.4 and 8.5 fl in CL and control groups on days 0, 7 and 14, respectively; r<0.05 for comparison between groups on days 7 and 14).

CONCLUSION

In pts with NSTEACS both thienopyridines attenuated acute phase elevation of vWF. The use of TIC in UFH treated pts was associated with indirect signs of decreased thrombin activity and some inhibition of fibrinolysis while the use of CL in enoxaparin treated pts was associated with signs of activation of fibrinolysis.