Loading With 600 mg Clopidogrel in Patients With Coronary Artery Disease With and Without Chronic Clopidogrel Therapy

Abstract

Background-It is not known whether further suppression of platelet function can be achieved with clopidogrel beyond that provided by currently recommended loading and maintenance doses. We performed a comparative assessment of the antiplatelet effects of a 600-mg loading dose of clopidogrel given to patients with and without chronic clopidogrel therapy. Methods and Results-Those eligible for this prospective study were aspirin-treated patients with suspected or documented coronary artery disease admitted to hospital for coronary angiography. Two series of 20 consecutive patients each were assessed in this study. The first series included patients who had never received clopidogrel (first-use group); the second series included patients on chronic therapy with a daily dose of 75 mg clopidogrel for Ն1 month (chronic therapy group). Blood samples were drawn before and 6 hours after oral administration of 600 mg clopidogrel for aggregometry and flow cytometry studies. In the first-use group, loading with 600 mg clopidogrel inhibited ADP 5 mol/L-induced platelet aggregation from 90Ϯ9% to 51Ϯ19% (PϽ0.001). In the chronic therapy group, loading with 600 mg clopidogrel yielded further inhibition of ADP 5 mol/L-induced platelet aggregation in addition to that achieved by the maintenance dose of 75 mg/d, from 52Ϯ14% to 33Ϯ12% (PϽ0.001). In both groups, 600 mg clopidogrel loading significantly inhibited ADP-induced expression of glycoprotein IIb/IIIa and P-selectin receptors. Conclusions-Further platelet inhibition can be achieved with clopidogrel in addition to that provided by currently recommended loading and maintenance doses. Higher doses may be warranted after assessment of their clinical efficacy and safety.

High Versus Standard Clopidogrel Maintenance Dose After Percutaneous Coronary Intervention and Effects on Platelet Inhibition, Endothelial Function, and Inflammation. Results of the Armyda-150 Mg (Antiplatelet Therapy for Reduction of Myocardial Damage During Angioplasty) Randomized Study

“…Уста-новлено, что у больных, получающих клопидогрел в под-держивающей дозе 75 мг/день, кратковременное усиление ингибирования тромбоцитов может быть достигнуто дополнительной нагрузочной дозой (600 мг) [10], а длительный эффект требует повышения суточ-ной дозы до 150 мг [11]. Ретроспективно показано, что у больных, принимавших клопидогрел в нагрузочной…”

Pharmacokinetics of clopidogrel in patients with stent thrombosis

“…Recently, we assessed platelet aggregation in 20 consecutive patients without a history of stent thrombosis under chronic clopidogrel treatment before and after administration of an additional 600 mg loading dose of clopidogrel [15]. Mean 5 lmol L )1 ADP-induced platelet aggregation was lower in this group of patients [15] (52.0%) compared with the seven stent thrombosis patients investigated here (66.6%). In addition, mean IPA achieved with additional clopidogrel loading was higher in the 20 patients [15] (36.5%) compared with the seven stent thrombosis patients (28.2%).…”

“…Diminished intestinal absorption does not seem to be a major determinant of clopidogrel resistance in our stent thrombosis patients, as demonstrated by similar c max values of unchanged clopidogrel in patients and controls [13]. Recently, we assessed platelet aggregation in 20 consecutive patients without a history of stent thrombosis under chronic clopidogrel treatment before and after administration of an additional 600 mg loading dose of clopidogrel [15]. Mean 5 lmol L )1 ADP-induced platelet aggregation was lower in this group of patients [15] (52.0%) compared with the seven stent thrombosis patients investigated here (66.6%).…”

Clinical Considerations with the Use of Antiplatelet Therapy in Patients Undergoing Percutaneous Coronary Intervention

“…Given the significantly better platelet inhibition demonstrated with a 600 mg loading dose of clopidogrel in patients with coronary artery disease (CAD) already receiving standard 75 mg clopidogrel maintenance dosing, 6 the impact of higher maintenance doses on platelet inhibition was evaluated by von Beckerath and colleagues. 7 That double-blind study randomized 60 patients taking chronic ASA therapy who had undergone PCI and received a 600 mg loading dose to a clopidogrel maintenance dose of 75 or 150 mg/day.…”