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J Am Coll Cardiol. 2014 Jul 29;64(4):361-8. doi: 10.1016/j.jacc.2014.03.051.

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

Author information

1
Universitaets Herzzentrum Freiburg, Klinik für Kardiologie und Angiologie II, Bad Krozingen, Germany.
2
TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
3
Harvard Clinical Research Institute, Boston, Massachusetts.
4
Center for Platelet Research Studies, Boston Children's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
5
University of Florida College of Medicine-Jacksonville, Jacksonville, Florida.
6
TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. Electronic address: jmega@partners.org.

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).

KEYWORDS:

clopidogrel; nonresponder; platelet reactivity; variability

PMID:
25060370
DOI:
10.1016/j.jacc.2014.03.051
[Indexed for MEDLINE]
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