medigraphic.com

2000, Number 5

<< Back Next >>

Arch Cardiol Mex 2000; 70 (5)

Efficacy of clopidogrel as inhibitor of adp-induced platelet aggregation. A study in patients with coronary artery disease

Izaguirre ÁR, Peña A, González PH, Ramírez GA, González VH, Quiroz A, Cortina E, Huerta M, Lupi E

Language: Spanish
References: 28
Page: 472-480
PDF size: 229.42 Kb.


ABSTRACT

Acetyl-salicylic acid inhibits thromboxane A2 production and reduces the risk of vascular occlusive events by 20 to 25%. Ticlopidine inhibits ADP-dependent platelet aggregation and reduces the same risk by 30 to 35%, but produces some adverse effects. Clopidogrel is a ticlopidin-derived antiplatelet-drug, with the same mechanism of action; reduces the expression of the glycoprotein IIb/IIIa, the fibrinogen receptor on the platelet surface. Clopidogrel has the same clinical efficacy of ticlopidin and lowers the incidence of adverse effects. In this study, we evaluated the effects of one daily dosis of 75 mg of clopidogrel on platelet function in 33 subjects with coronary artery disease. Before treatment and after the 6th and 12th week, the following parameters were evaluated: 5 µM-ADP and 20 µg/mL collagen-induced platelet aggregation, bleeding time and fibrinogen concentration. In basal and in the 6th and 12th week samples, ADP-induced platelet aggregation was 90.7% ± 13.2, 54.6% ± 23.2 and 49.2% ± 23.7 respectively, that represents a significant reduction of 38.6% and 44.4%. Reduction of collagen-induced platelet aggregation was not significative. Plasmatic fibrinogen did not suffer variation during treatment. Bleeding time was significant prolonged from 4.1 minutes to 15.4 and 14.6 minutes (3.7-3.5 times compared with the test before treatment). There were no haemorrhagic complications, only digestive discomfort in fewer than 3% of patients. We concluded that clopidogrel is a safe and efficacious drug for patients, it efficiently reduces ADP-induced platelet aggregation and prolongs bleeding time.


REFERENCES

  1. Murray CJ, Lopez AD: Mortality by cause for eight regions of the world: Global Burden of Disease Study. Lancet 1997; 1349 (9061): 1269-1276.

  2. Olvera S: Epidemiología de la ateroesclerosis coronaria. En Posadas C. Dislipidemias y Ateroesclerosis. México, Interamericana-McGraw-Hill 1995; 29-41.

  3. Chávez-Domínguez R: Factores de riesgo lipídicos. Epidemiología general de la ateroesclerosis en México. En Alcocer-Díaz-Barreiro L. Pautas en Cardiología Preventiva. México, Ediciones de la Sociedad Mexicana de Cardiología. Grupo MIND 1999: 1-21.

  4. Ware JA, Heistad DD: Platelet-Endothelium interactions. New Engl J Med 1993; 328: 628-35.

  5. Fischer A, Gutstein DE, Fuster V: Thrombosis and coagulation abnormalities in the acute coronary syndromes. Cardiol Clin 1999; 17(2): 283-294.

  6. Antiplatelet Trialists’ Collaboration. Colaborative overview of randomised trials of antiplatelet therapy I. Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. British Medical Journal 1994; 308: 81-106.

  7. Hass WK, Easton JD, Adams JP Jr, Pryse-Philips W, Molony BA, Anderson S, et al: A randomized trial comparing ticlopidine hidrochloride with aspirin for the prevention of stroke in high-risk patients. New Eng J Med 1989; 321: 501-507.

  8. Gent M, Blakely JA, Easton JB: The Canadian American Ticlopidine Study (CATS) in thromboembolic stroke. Lancet 1989; 1: 1215-1220.

  9. Balsano F, Rizzon P, Violi F: Antiplatelet treatment with ticlopidine in unestable angine: a controlled multicenter clinical trial. Circulation 1990; 82: 17-26.

  10. Caprie Steering Commitee: A randomised, blinded trial of clopidogrel versus aspirin in patients at risk of ischemic events (Caprie). Lancet 1996; 348: 1329-1349.

  11. Harker LA, Marzec UM, Kelly AB, Chronos NR, Sundell IB, Hanson SR, et al. Clopidogrel inhibition of stent, graft, and vascular thrombogenesis with antithrombotic enhancement by aspirin in nonhuman primates. Circulation 1998; 22: 2461-2469.

  12. Miller JL: Platelet function testing: an improved approach utilizing lumi-aggregation and interactive computer system. Am J Clin Pathol 1984; 81: 471-476.

  13. Hechler B, Eckly A, Ohlmann P, Cazaneve JP, Gachet C: The PSY1 receptor, necessary but no sufficient to suport full ADP-induced platelet aggregation, is not the target of the drug clopidogrel. Br J Hematol 1998; 103: 858-66.

  14. Weber AA, Reimann S, Schor K: Specific inhibition of ADP-induced platelet aggregation by Clopidogrel in vitro. Br J Pharmacol 1999; 126: 415-420.

  15. Mills DC, Puri R, Hu CJ, Minniti C, Grana G, Freedman MD, et al: Clopidogrel inhibits the binding of ADP analogues to the receptor mediating inhibition of platelet adenylate cyclase. Arterioscler Thromb 1992; 124: 430-436.

  16. Takahashi O: Characteristics of rat platelets and relative contributions of platelets and blood coagulation to hemostasis. Food Chem Toxicol 2000; 38: 203-218.

  17. Schwarz UR, Geiger J, Walter U, Eigenthaler M: Flow citometry analysis of intracellular VASP phosphorylation, the assessment of activating and inhibitory signal transduction patways in human platelets-definition and detection of ticlopidine/clopidogrel effects. Thromb Haemost 1999; 82: 1145-1152.

  18. Thebault JJ, Kieffer G, Lowe GD, Nimmo WS, Cariou R: Repeated-dose pharmacodynamics of clopidogrel in healthy subjects. Semin Thromb Hemost 1999; 25 Suppl 2: 9-14.

  19. Denninger MH, Necciari J, Serre-Lacroix E, Sissmann J: Clopidogrel antiplatelet activity is independent of age and presence of atherosclerosis. Semin Thromb Hemost 1999; 25 Suppl 2: 41-45.

  20. David JL, Limet R: Antiplatelet activity of clopidogrel in coronary artery bypass graft surgery patients. Thromb Haemost 1999; 82: 1417-1421.

  21. Savcic M, Hauert J, Bachmann F, Wyld PJ, Geudelin B, Cariou R: Clopidogrel loading dose regimens: kinetic profile of pharmacodynamic response in healthy subjects. Semin Thromb Hemost 1999; 25 Suppl 2: 15-19.

  22. Herbert JM, Dol F, Bernat A, Falotico R, Lalq A, Savi P: The antiaggregating and antithrombotic activity of clopidogrel is potentiated by aspirin in several experimental models in the rabbit. Thromb Haemost 1998; 80: 512-518.

  23. Berger PB, Bell MR, Rihal CS, Ting H, Barsness G, Garratt K, et al: Clopidogrel versus ticlopidine after intracoronary stent placement. J Am Coll Cardiol 1999; 34: 1891-1894.

  24. Müller C, Büttner HJ, Petersen J, Roskamm H: A randomized comparison of clopidogrel and aspirin versus ticlopidine and aspirin after the placement of coronary artery stents. Circulation 2000; 1101: 590-593.

  25. Mishkel GJ, Aguirre FV, Ligon RW, Rocha-Singh KJ, Lucore CL: Clopidogrel as adjunctive antiplatelet therapy during coronary stenting. J Am Coll Cardiol 1999; 34: 1884-1890.

  26. Uchiyama S, Yamazaki M, Maruyama S, Handa M, Ikeda Y, Fukuyama M: Shear-induced platelet aggregation in cerebral ischemia. Stroke 1994; 25: 1547-1551.

  27. Walters TK, Mitchell DC, Wood RF: Low-dose aspirin fails to inhibit increased platelet reactivity in patients with peripheral vascular disease. Br J Surg 1993; 80: 1266-1268.

  28. Schrör K: Aspirin and platelets: the antiplatelet action of aspirin and its role in thrombosis treatment and prophylaxis. Sem Throm Hemos 1997; 23: 349-356.




2020     |     www.medigraphic.com