Clopidogrel maintenance dose and platelet aggregation - Clopidogrel maintenance dose and platelet aggregation


The goal of the trial was to evaluate the effect of clopidogrel 75 mg versus 150 mg dose on platelet aggregation among patients undergoing elective percutaneous coronary intervention (PCI).

Study Design

Study Design:

Patients Screened: 249
Patients Enrolled: 60
Mean Follow Up: 30 days
Mean Patient Age: Mean age 64 years
Female: 8

Patient Populations:

Chronic aspirin therapy, elective PCI in the prior 12 hours, and administration of a 600 mg loading dose of clopidogrel pre-PCI


PCI due to unstable angina or acute myocardial infarction, hemodynamically unstable, stroke within 3 months, malignancies, active bleeding and bleeding diatheses, oral anticoagulation therapy with a coumarin derivative, recent treatment within 30 days with a glycoprotein IIb/IIIa antagonist or other antiplatelet drugs (particularly clopidogrel) except for aspirin, platelet count <100 x 109/L, serum creatinine >2 mg/dl, or liver disease resulting in bilirubin >2 mg/dl

Primary Endpoints:

Maximal 5 µM ADP-induced platelet aggregation assessed with conventional aggregometry 30 days after PCI

Drug/Procedures Used:

Patients who had been treated pre-PCI with a 600 mg clopidogrel loading dose were randomized in a double-blind manner to a 30-day clopidogrel maintenance dose of 75 mg (n = 29) or 150 mg (n = 31). Platelet function testing was performed at 30 days.

Concomitant Medications:


Principal Findings:

Mean baseline platelet count was 220 x 109/L. Half of the patients in the study had hypercholesterolemia. History of diabetics was present in 22.6% of the 150 mg/day group and 34.5% of the 75 mg/day group. There were two TIMI minor bleeds in each group and no major bleed in either group. One patient in the 150 mg group had a myocardial infarction and one patient in the 75 mg group had target vessel revascularization.

The primary endpoint of maximal 5 µM adenosine diphosphate (ADP)-induced platelet aggregation 30 days after PCI was significantly lower in the 150 mg/day clopidogrel group compared with the 75 mg/day group (mean 45.1% vs. 65.3%, p < 0.001). Platelet-function inhibition using a bedside assay was also higher in the 150 mg group (60.0 vs. 117 P2Y12 Reaction Units [PRU], p = 0.004).


Among patients undergoing elective PCI who were pre-treated with a 600 mg loading dose of clopidogrel, maintenance therapy with a 150 mg/day dose of clopidogrel was associated with a reduction in platelet aggregation at 30 days post-PCI compared with the 75 mg/day group.

Recent studies such as ALBION and ARMYDA-2 have evaluated using a higher loading dose of clopidogrel than the 300 mg recommended dose among patients undergoing elective PCI. However, both studies focused on the loading dose of clopidogrel, not the maintenance dose. In the present study, all patients were pretreated with a 600 mg loading dose. Despite the higher loading dose, a 150 mg/day maintenance dose was associated with a reduction in platelet aggregation at 30 days. The clinical efficacy and bleeding implications of this reduction in platelet aggregation with a higher maintenance dose will need to be further explored in a much larger study. The OASIS-7 trial will evaluate a strategy of high loading dose (600 mg) followed by a high maintenance dose (150 mg/day for 1 week) compared with the standard loading dose (300 mg) followed by the standard maintenance dose (75 mg/day) in patients with acute coronary syndrome.


von Beckerath N, Kastrati A, Wieczorek A, et al. A double-blind, randomized study on platelet aggregation in patients treated with a daily dose of 150 or 75 mg of clopidogrel for 30 days. Eur Heart J 2007 Feb 1; epub before print.

Clinical Topics: Acute Coronary Syndromes, Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Homozygous Familial Hypercholesterolemia, Interventions and ACS

Keywords: Acute Coronary Syndrome, Myocardial Infarction, Platelet Aggregation Inhibitors, Platelet Function Tests, Platelet Count, Coronary Disease, Ticlopidine, Hypercholesterolemia, Percutaneous Coronary Intervention, Platelet Aggregation, Diabetes Mellitus

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