[Non ST elevation acute coronary syndrome. Some characteristics of coagulation and von Willebrand factor during short term use of ticlopidine or clopidogrel].
Levels of some markers of coagulation and platelet activation such as prothrombin fragment 1+2 (F1+2) thrombin-antithrombin complex (TAT) and von Willebrand factor (vWF), are related to outcome in non ST-segment elevation acute coronary syndrome (NSTEACS). Effects of thienopyridines ticlopidine and clopidogrel on acute changes of these parameters in patients with NSTEACS are not well investigated.


OBJECTIVE
To study changes of markers of coagulation and platelet activation during short term use of ticlopidine and clopidogrel in NSTEACS patients treated with aspirin and antithrombin.


METHODS
Patients with NSTEACS, treated with aspirin and unfractionated heparin (n=37, <48 hours from pain onset, Braunwald class IIIb) were randomized to open ticlopidine (n=19, 500 mg BID loading dose for 2 days and 250 mg BID for subsequent 5 days) or no ticlopidine (n=18). In another substudy with the same design 19 aspirin and enoxaparin treated patients were randomized to clopidogrel (n=10, 300 mg loading dose and 75 mg/day for subsequent 6 days) or no clopidogrel (n=9). Levels of F1+2, TAT and vWF were measured at baseline, on days 1, 3, 7 and 14 (7 days after discontinuation of thienopyridines).


RESULTS
At baseline values of parameters studied were similar in each pair (thienopyridine - control) of patient groups. Compared with their controls ticlopidine treated patients in 7 days after ticlopidine discontinuation had lower levels of TAT (2.77 and 3.61 ng/ml, r<0.05) and fibrinogen (3.16 and 3.84 g/l, r<0.05). The level of vWF in ticlopidine treated patients was lower relative to control group on days 3 (163 and 186%, r<0.05) and 14 (144 and 173%, p<0.01). In substudy with clopidogrel differences between groups existed only in vWF levels. In clopidogrel treated patients the level vWF was lower relative to controls on days 3 (152 and 185%, r<0.05) and 7 (141 and 166%, r<0.05).


CONCLUSIONS
Short term use of ticlopidine in patients with NSTEACS treated with aspirin and unfractionated heparin was associated with lower levels of TAT and fibrinogen (relative to control group) on day 14. This could be interpreted as delayed effect of ticlopidine on thrombin activity. Both ticlopidine and clopidogrel used in regimes with loading doses in NSTEACS patients treated with aspirin and antithrombin prevented acute phase elevation of vWF.
Research Institute for Physicochemical Medicine, Laboratory of Clinical Cardiology and Center of Atherosclerosis, ul. Malaya Pirogovskaya 1a, 119828 Moscow, Russia.
O V
OV
Averkov
N N
NN
Slavina
N A
NA
Gratsianskiĭ
D000208:Acute Disease; D000328:Adult; D000789:Angina, Unstable / Q000097:blood / Q000188:drug therapy*; D000925:Anticoagulants / Q000008:administration & dosage / Q000627:therapeutic use; D001241:Aspirin / Q000008:administration & dosage / Q000627:therapeutic use; D001777:Blood Coagulation; D000077144:Clopidogrel; D003627:Data Interpretation, Statistical; D004562:Electrocardiography; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D006493:Heparin / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D008297:Male; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D013577:Syndrome; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D014841:von Willebrand Factor / Q000032:analysis*
D000925:Anticoagulants; D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D014841:von Willebrand Factor; D006493:Heparin; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin