title: Effectiveness of reloading to overcome clopidogrel nonresponsiveness in patients with acute myocardial infarction.
abstract: Whether increasing doses of clopidogrel can overcome nonresponsiveness was evaluated. Clopidogrel nonresponsiveness was found in up to 25% of treated patients and was associated with worse prognosis in patients with acute coronary syndrome and patients undergoing coronary intervention. Adenosine diphosphate (ADP)-induced platelet aggregation was prospectively determined on day 4 of acute myocardial infarction in 200 consecutive patients, who received clopidogrel 300 mg as a loading dose and 75 mg/day thereafter. Thirty patients (15%) had ADP-induced platelet aggregation >or=80% using light transmittance aggregometry and were considered clopidogrel nonresponders. Nonresponders were reloaded with clopidogrel 600 mg, followed by 150 mg/day for 4 weeks. A 75-mg/day dose was resumed thereafter. ADP-induced platelet aggregation was reassessed 4 hours after reloading and biweekly for 10 weeks. Flow cytometry was used to determine platelet P-selectin expression and fibrinogen binding before and 4 hours after reloading. ADP-induced platelet aggregation significantly decreased 4 hours after reloading (from 83 +/- 6% to 56 +/- 14%; p <0.01). The decrease in platelet aggregation was maintained throughout the 4-week doubled maintenance dose. After resuming a maintenance dose of 75 mg/day, ADP-induced platelet aggregation returned to 66 +/- 12% (p <0.001), and 5 patients (17%) had ADP-induced platelet aggregation >or=80%. Flow cytometry showed a significant decrease in P-selectin expression (from 37 +/- 16% to 26 +/- 13%; p <0.01) and fibrinogen binding (from 84 +/- 7% to 70 +/- 13%; p <0.01) in ADP-stimulated platelets 4 hours after reloading. In conclusion, clopidogrel reloading and increased maintenance dose may overcome clopidogrel nonresponsiveness in patients with acute myocardial infarction.
authors: Heart Institute, Sheba Medical Center, Tel Hashomer and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. shlomi.matetzky@sheba.health.gov.il
authors: Shlomi
authors: S
authors: Matetzky
authors: Paul
authors: P
authors: Fefer
authors: Boris
authors: B
authors: Shenkman
authors: David
authors: D
authors: Varon
authors: Naphtali
authors: N
authors: Savion
authors: Hanoch
authors: H
authors: Hod
mesh_terms: D001792:Blood Platelets / Q000378:metabolism; D000077144:Clopidogrel; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D005260:Female; D005340:Fibrinogen / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D019007:P-Selectin / Q000096:biosynthesis; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D011446:Prospective Studies; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016896:Treatment Outcome
chemical_list: D019007:P-Selectin; D010975:Platelet Aggregation Inhibitors; D005340:Fibrinogen; D000077144:Clopidogrel; D013988:Ticlopidine