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Platelet anti-aggregating activity and tolerance of clopidogrel in atherosclerotic patients
1Laboratoire de Recherche sur l'Hémostase et la Thrombóse, Hôpital Purpan, Toulouse, France.
Insights
Clopidogrel effectively reduced platelet aggregation and bleeding time in atherosclerotic patients, similar to ticlopidine. A dose of 75 mg daily was selected for further trials.
Area of Science:
- Cardiology
- Pharmacology
- Hematology
Background:
- Atherosclerosis poses a significant risk for ischemic events.
- Antiplatelet therapy is crucial for secondary prevention in these patients.
Purpose of the Study:
- To determine the optimal dose of clopidogrel for a large-scale clinical trial.
- To compare the anti-aggregating activity and tolerability of clopidogrel to ticlopidine.
Main Methods:
- Multicenter study with 150 atherosclerotic patients randomized to clopidogrel (10-100 mg OD), ticlopidine (250 mg BID), or placebo.
- Assessed ADP and collagen-induced platelet aggregation, bleeding time, and clinical/biological tolerability over 28 days.
Main Results:
- Clopidogrel demonstrated a dose-related inhibition of platelet aggregation (29-44%) and prolonged bleeding time (1.5-1.7x).
- Effects were comparable to ticlopidine, with good clinical tolerability (97.5%) and no hematological adverse events.
- The 75 mg once-daily dose was identified as suitable for further investigation.
Conclusions:
- Clopidogrel exhibits dose-dependent antiplatelet activity and bleeding time prolongation.
- The 75 mg daily dose is a promising candidate for evaluating clopidogrel's efficacy in secondary prevention of ischemic events.
Abstract:
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 trail 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 microM) 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.