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Variability of individual platelet reactivity over time in patients treated with clopidogrel: insights from the ELEVATE-TIMI 56 trial.

Abstract：

BACKGROUND:The degree of antiplatelet response to clopidogrel has been associated with clinical outcomes. Studies have investigated whether adjustment of antiplatelet therapies based on a single platelet function test is beneficial. OBJECTIVES:The aim of the study was to test the stability of platelet reactivity measurements over time among patients treated with standard and double doses of clopidogrel. METHODS: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 2 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). RESULTS:In total, the mean platelet reactivity and the total number of nonresponders (PRU ≥230) with clopidogrel did not change between 2 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 2 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. CONCLUSIONS:Measurements of platelet reactivity vary over time in a significant proportion of patients. Thus, treatment adjustment according to platelet function testing at a single time point might not be sufficient for guiding antiplatelet therapy in clinical or research settings. (Escalating Clopidogrel by Involving a Genetic Strategy-Thrombolysis In Myocardial Infarction 56 [ELEVATE-TIMI 56]; NCT01235351).

journal_name

J Am Coll Cardiol

journal_title

Journal of the American College of Cardiology

authors

Hochholzer W,Ruff CT,Mesa RA,Mattimore JF,Cyr JF,Lei L,Frelinger AL 3rd,Michelson AD,Berg DD,Angiolillo DJ,O'Donoghue ML,Sabatine MS,Mega JL

doi

10.1016/j.jacc.2014.03.051

subject

Has Abstract

pub_date

2014-07-29 00:00:00

pages

361-8

issue

eissn

0735-1097

issn

1558-3597

pii

S0735-1097(14)02602-3

journal_volume

pub_type

杂志文章,多中心研究,随机对照试验

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Variability of individual platelet reactivity over time in patients treated with clopidogrel: insights from the ELEVATE-TIMI 56 trial.