Matching the Evaluation of the Clinical Efficacy of Clopidogrel to Platelet Function Tests Relevant to the Biological Properties of the Drug
Benoît Labarthe, PharmD*,
Pierre Théroux, MD, FACC*,*,
Michaël Angioï, MD, PhD and
Marta Ghitescu*
* Department of Medicine, Montreal Heart Institute and University of Montreal, Montreal, Quebec, Canada
Département de Cardiologie, Hôpitaux de Brabois, Centre Hospitalier Universitaire de Nancy, Nancy, France
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Figure 1 Design of the double-blind placebo-controlled randomized study performed in normal volunteers (Study 2).
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Figure 2 Aggregation curves from a normal individual, obtained after the addition of adenosine 5'-diphosphate (ADP) 2.5 µM and thrombin receptor agonist peptide (TRAP) 2.5 µM in platelet-rich plasma at baseline (left); 24 h after a loading dose of clopidogrel (middle); and 24 h later, after a dose of clopidogrel 75 mg and aspirin (ASA) 300 mg (right). Disintegration is minimal at baseline and nearly complete after clopidogrel in the presence of ADP and significant in the presence of TRAP. Aspirin added no additional disintegration.
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Figure 3 Inhibition of platelet functions in platelet-rich plasma prepared in sodium citrate (open boxes) versus r-hirudin and D-phenylalanyl-prolyl-arginine chloromethyl ketone (hirudin/PPACK) (boxes with vertical lines) (*p < 0.05). (a) Peak aggregation, (b) late aggregation, (c) P-selectin expression, (d) glycoprotein (GP) IIb/IIIa activation by monoclonal antibody binding activated GP IIb/IIIa receptors (PAC-1) measure after agonist stimulation with either a thrombin receptor activating peptide-6 (left panels) or adenosine 5'diphosphate (ADP) (right panels). Horizontal lines are medians, boxes are the interquartile range, whiskers are the 5th and 95th percentiles, and p values were obtained using the Wilcoxon signed-rank test; *p < 0.05.
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Figure 4 Percent disaggregation from peak aggregation to six min after the addition of adenosine 5'-diphosphate (ADP) (top) and thrombin receptor agonist peptide (TRAP) (bottom) in healthy volunteers, at baseline on Day 1, 24 h after the first drug administration on Day 2, and 24 h after the last drug administration on Day 3. Open boxes are either at baseline or after placebo, boxes with diagonal lines are after aspirin, boxes with vertical lines are after clopidogrel (doses shown in Fig. 1, and an actual tracing in Fig. 2). The horizontal lines are medians, the boxes are the interquartile range, whiskers are the 5th and 95th percentiles, and p values were obtained by the Wilcoxon signed-rank test; *p < 0.05.
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