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Updated: Jun 19, 2026

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
Published on: December 9, 2015
Clopidogrel resistance: fact and fiction
J W van Werkum1, A A C M Heestermans, V H M Deneer
1Department of Cardiology, St. Antonius Hospital, Nieuwegein, The Netherlands.
Insights
Clopidogrel with aspirin reduces thrombotic events, but response varies greatly. Understanding factors like absorption and drug interactions is key to managing clopidogrel resistance.
Area of Science:
- Pharmacology
- Cardiology
- Thrombosis Research
Background:
- Clopidogrel and aspirin combination therapy is vital for preventing thrombotic events in acute coronary syndromes and after percutaneous coronary intervention.
- Significant interindividual variability in patient response to clopidogrel necessitates further investigation.
Purpose of the Study:
- To explore the factors contributing to variable patient responses to clopidogrel.
- To highlight the clinical relevance and prevalence of inadequate clopidogrel response.
- To recommend future research directions for assessing clopidogrel resistance.
Main Methods:
- Review of existing literature on clopidogrel response variability.
- Identification of factors influencing clopidogrel efficacy, including dosing, absorption, drug metabolism (CYP450 3A4/5), drug interactions, and genetic polymorphisms.
- Discussion of various platelet function assays used to measure clopidogrel response.
Main Results:
- Inadequate clopidogrel response rates vary widely based on measurement methods and definitions.
- Factors such as dosing, intestinal absorption, CYP450 activity, drug-drug interactions, and genetic variations impact clopidogrel response.
- Clinical relevance of inadequate clopidogrel response has been demonstrated in recent studies.
Conclusions:
- Accurate assessment of clopidogrel resistance requires standardized, sensitive assays focusing on P2Y12 receptor inhibition.
- Future research should utilize rapid, simple tests like vasodilator-stimulated phosphoprotein (VASP) assay or platelet aggregate stabilization measurements.
- Understanding and addressing clopidogrel resistance is crucial for optimizing antiplatelet therapy outcomes.
Abstract:
The antiplatelet agent clopidogrel in combination with aspirin has been shown to reduce thrombotic events in patients with acute coronary syndromes and/or who are undergoing percutaneous coronary intervention. However, a large interindividual response variability to clopidogrel has been described. The reported rates of inadequate clopidogrel response vary considerably depending on the definition and methodologies used to measure the inhibition of platelet function. Recently, several (small) studies have demonstrated the clinical relevance of an inadequate response to clopidogrel. Moreover, several factors have been associated with a high interindividual variability in response to clopidogrel. These are: dosing, impaired intestinal absorption, cytochrome P450 3A4 and 3A5 activity, drug-drug interactions, polymorphisms of the receptors involved in the process of arterial thrombosis and hemostasis, and the method of measurement of platelet function. Future research for the evaluation of clopidogrel resistance should be based on the assessment of selective P2Y12 receptor inhibition (e.g., the vasodilator-stimulated phosphoprotein-assay or the measurement of stabilization of platelet aggregates) with quick and simple tests. Only then can we reveal the true prevalence and impact of clopidogrel resistance.
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