Variability of Individual Platelet Reactivity Over Time in Patients Treated With Clopidogrel: Insights From the ELEVATE–TIMI 56 Trial

Study Questions:

What is the stability of platelet reactivity measurements over time among patients treated with standard and double doses of clopidogrel?


The ELEVATE–TIMI 56 (Escalating Clopidogrel by Involving a Genetic Strategy–Thrombolysis In Myocardial Infarction 56) investigators genotyped 333 patients with coronary artery disease and randomized them to various clopidogrel regimens. Patients with at least two platelet function results on the same maintenance dose of clopidogrel (75 mg or 150 mg) were analyzed. Platelet aggregation was measured using P2Y12 reaction units (PRU).


In total, the mean platelet reactivity and the total number of nonresponders (PRU ≥230) with clopidogrel did not change between two periods for the 75 mg (22.4% vs. 21.9%; p = 0.86) and 150 mg doses of clopidogrel (11.5% vs. 11.5%; p = 1.00). In contrast, when evaluating each patient individually, 15.7% of patients taking clopidogrel 75 mg and 11.4% of patients taking 150 mg had a change in their responder status when tested at two different time points (p < 0.001). Despite being treated with the same dose of clopidogrel, >40% of patients had a change in PRU >40 on serial sampling, which approximates the average PRU difference caused by increasing the clopidogrel dose from 75 mg to 150 mg.


The authors concluded that measurements of platelet reactivity vary over time in a significant proportion of patients.


The study reports that measurements of platelet reactivity vary over time in a significant proportion of patients, even when higher maintenance doses of clopidogrel are used. Based on these results, treatment adjustment according to platelet function testing at a single time point might not be sufficient for guiding antiplatelet therapy in either clinical or research settings. Future studies that use measurements of platelet inhibition in patients exposed to clopidogrel should consider the value of serial data on platelet inhibition instead of testing at a single time point.

Clinical Topics: Atherosclerotic Disease (CAD/PAD)

Keywords: Coronary Artery Disease, Platelet Aggregation Inhibitors, Platelet Function Tests, Platelet Aggregation, Ticlopidine

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