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DOI: 10.1055/s-0038-1650689
Platelet Anti-Aggregating Activity and Tolerance of Clopidogrel in Atherosclerotic Patients
Publication History
Received 29 May 1996
Accepted after revision 25 July 1996
Publication Date:
11 July 2018 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/199606/lookinside/thumbnails/10-1055-s-0038-1650689-1.jpg)
Summary
The anti-aggregating activity of five rising doses of clopidogrel has been compared to that of ticlopidine in atherosclerotic patients. The aim of this study was to determine the dose of clopidogrel which should be tested in a large scale clinical trial of secondary prevention of ischemic events in patients suffering from vascular manifestations of atherosclerosis [CAPRIE (Clopidogrel vs Aspirin in Patients at Risk of Ischemic Events) trial]. A multicenter study involving 9 haematological laboratories and 29 clinical centers was set up. One hundred and fifty ambulatory patients were randomized into one of the seven following groups: clopidogrel at doses of 10, 25, 50,75 or 100 mg OD, ticlopidine 250 mg BID or placebo. ADP and collagen-induced platelet aggregation tests were performed before starting treatment and after 7 and 28 days. Bleeding time was performed on days 0 and 28. Patients were seen on days 0, 7 and 28 to check the clinical and biological tolerability of the treatment. Clopidogrel exerted a dose-related inhibition of ADP-induced platelet aggregation and bleeding time prolongation. In the presence of ADP (5 \lM) this inhibition ranged between 29% and 44% in comparison to pretreatment values. The bleeding times were prolonged by 1.5 to 1.7 times. These effects were non significantly different from those produced by ticlopidine. The clinical tolerability was good or fair in 97.5% of the patients. No haematological adverse events were recorded. These results allowed the selection of 75 mg once a day to evaluate and compare the antithrombotic activity of clopidogrel to that of aspirin in the CAPRIE trial.
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References
- 1 Herbert JM, Frehel D, Vallee E, Kieffer G, Gouy D, Berger Y, Defreyn G, Maffrand JP. Clopidogrel, a novel antiplatelet and antithrombotic agent. Cardiovasc Drug Rev 1993; 2: 180-198
- 2 Mills DCB, Puri R, Hu CJ, Minnity C, Grana G, Freedman MD, Colman RW. Clopidogrel inhibits the binding of ADP analogues to the receptor mediating inhibition of platelet adenylate cyclase. Arterioscler Thromb 1992; 2: 430
- 3 Savi P, Laplace MC, Maffrand JP, Herbert JM. Binding of [3H]-2 me-thylthio ADP to rat platelets. Effect of clopidogrel and ticlopidine. J Pharmacol Exp Ther 1994; 269: 772-777
- 4 Gachet C, Cattaneo M, Ohlmann P, Hechler B, Lecchi A, Chevalier J, Cas-sel D, Mannucci PM, Cazenave JP. Purinoceptors on blood platelets: further pharmacological and clinical evidence to suggest the presence of two ADP receptors. Br J Haematol 1995; 9: 434-444
- 5 Gachet C, Savi P, Ohlmann P, Maffrand JP, Jakobs KH, Cazenave JP. ADP receptor induced activation of guanine nucleotide binding proteins in rat platelet membranes. An effect selectively blocked by the thienopyridine clopidogrel. Thromb Haemost 1992; 68: 79-83
- 6 Dunn FW, Soria J, Soria C, Thomaidis A, Lee H, Coeur JP. In vivo effects of ticlopidine on fibrinogen platelet cofactor activity and binding of fibrinogen on platelets. Agents Actions 1984; 15: 97-103
- 7 Kieffer G, Caplain H, Thiercelin JF, Thebault JJ. Tolerance and pharmacological activity of a new antiplatelet agent clopidogrel (SR 25990 C) in normal healthy volunteers after single increasing administrations. Thromb Haemost 1989; 62: 411 (abst)
- 8 Caplain H, Kieffer G, Thiercelin JF, Thebault JJ. Tolerance and clinical pharmacology of repeated administration of clopidogrel (SR 25990 C) a new antiplatelet agent, at three dose levels in normal healthy volunteers. Thromb Haemost 1989; 62: 410 (abst)
- 9 Beker F. La classification de l’insuffisance arterielle des membres in-ferieurs de Leriche et Fontaine une reactualisation necessaire. Med et Hyg 1991; 49: 143-149
- 10 Ivy AC, Nelson D, Bucher G. The standardization of certain factors in the cutaneous venostasis bleeding time technique. Lab Clin Med 1941; 26: 1812-1822
- 11 Hass WK, Easton JD, Adams HP. A randomized trial comparing ticlopidine hydrochloride with aspirin for the prevention of stroke in high-risk patients. NEJM 1989; 321: 501-507
- 12 Molony B. Analysis of the side effects of ticlopidine in ticlopidine, platelets and vascular disease. Hass WK, Donald Easton J. (eds). New York: Springer Verlag: 1993: 117-139