Effectiveness of Reloading to Overcome Clopidogrel Nonresponsiveness in Patients With Acute Myocardial Infarction

Shlomi Matetzky*, Paul Fefer, Boris Shenkman, David Varon, Naphtali Savion, Hanoch Hod

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

37 Scopus citations


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 ≥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 ≥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.

Original languageEnglish
Pages (from-to)524-529
Number of pages6
JournalAmerican Journal of Cardiology
Issue number5
StatePublished - 1 Sep 2008


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