The Relation of Dosing to Clopidogrel Responsiveness and the Incidence of High Post-Treatment Platelet Aggregation in Patients Undergoing Coronary Stenting

• Published in: Journal of the American College of Cardiology Vol. 45; no. 9; pp. 1392 - 1396
• Main Authors: Gurbel, Paul A., Bliden, Kevin P., Hayes, Kevin M., Yoho, Jason A., Herzog, William R., Tantry, Udaya S.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 03.05.2005; Elsevier Science; Elsevier Limited
• Subjects: Adenosine Diphosphate; Aged; Biological and medical sciences; Blood platelets; Cardiology; Cardiology. Vascular system; Cardiovascular disease; Coronary heart disease; Coronary Stenosis - therapy; Coronary vessels; Dose-Response Relationship, Drug; Drug dosages; Drug therapy; Family medical history; Female; Heart; Humans; Incidence; Male; Medical sciences; Middle Aged; Patients; Platelet Aggregation - drug effects; Platelet Aggregation Inhibitors - administration & dosage; Postoperative Complications - prevention & control; Stents; Thrombosis; Ticlopidine - administration & dosage; Ticlopidine - analogs & derivatives; Treatment Outcome; PPP; post-PA; NR; GP; IR; ADP; ΔA; High; Human; Coronary artery; Instrumentation therapy; Cardiovascular disease; Instrumental dilatation; Epidemiology; Coronary heart disease; Phlebology; Stent; Incidence; Aggregation; Platelet; Clopidogrel; Circulatory system; Cardiology
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/j.jacc.2005.01.030

We determined the effect of clopidogrel dosing on the incidence of nonresponsiveness (NR) and high post-treatment platelet aggregation (post-PA). We have reported NR after a 300-mg loading dose. Limited information is available on the comparative effect of a 600-mg loading dose on the incidence of NR and high post-PA. Clopidogrel responsiveness and post-PA were measured in patients undergoing stenting (n = 190) randomly treated with either a 300-mg or a 600-mg clopidogrel load. Nonresponsiveness was defined as <10% absolute change in platelet aggregation, and high post-PA was defined as >75th percentile aggregation after 300 mg clopidogrel. Nonresponsiveness was lower after 600 mg compared to the 300-mg dose (8% vs. 28% and 8% vs. 32% with 5 and 20 μM ADP, respectively, p < 0.001). Among the patients with high post-PA after 300 mg clopidogrel, 62% to 65% had NR, whereas after the 600-mg dose, all of the patients with high post-PA had NR. A 600-mg clopidogrel loading dose reduces the incidence of NR and high post-PA as compared to a 300-mg dose. Higher dosing strategies and methods to confirm platelet inhibition should be further investigated in order to optimally use clopidogrel in patients undergoing stenting.