Anti-platelet therapy in (cardio)vascular disease

C. M. Hackeng*, J. M. Ten Berg, V. H.M. Deneer, H. J.T. Ruven, J. W. Van Werkum

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Recent years have witnessed significant advances in the treatment of patients with atherosclerotic (cardio) vascular disease and dual anti-platelet therapy with aspirin and clopidogrel (an ADP P2Y12 receptor antagonist) has become the cornerstone in the acute and long-term management of patients with coronary, cerebral and peripheral artery disease. Aspirin and clopidogrel interfere with platelet activation in complementary, but separate pathways. The result is an even stronger anti-platelet effect translating into superior antithrombotic protection without an increase in bleeding complications. A number of clinical trials have demonstrated the incremental benefit and efficacy of the combination of clopidogrel and aspirin therapy above and beyond that of aspirin alone. However, it has been demonstrated that the pharmacological response to clopidogrel is not uniform in all individuals and that low-response and/or non-response is associated with an increased risk of adverse outcomes, of which stent thrombosis is the most feared. Consequently, evaluation of the pharmacological response to antiplatelet therapy by monitoring platelet function inhibition has become an new field of interest and probably improves patients outcome. However, the road to platelet inhibition by clopidogrel is bumpy and the determination of the best measurement of clopidogrel response is a challenge. Clopidogrel is absorbed as a prodrug in the intestine by P-glycoprotein, after which 85% is inactivated and only 15% is metabolized through the intermediate 2-oxo-clopidogrel to it's active metabolite. This twostep metabolization process has been proposed to be mediated by CYP's 2C19, 2C9, 3A4, 3A5. The active metabolite irreversibly binds to the P2Y12 receptor, in which several Single Nucleotide Polymorphisms (SNP's) that possibly contribute to a decreased affinity for clopidogrel, are known. Finally, this blockade of the P2Y12 receptor leads to decreased platelet response to ADP. As the response of normal subjects to ADP has a wide variety, one might expect a large degree of variation in on-clopidogrel platelet function as well. We hypothesized that the only way to take all these variables into account is the endpoint of the mentioned process, platelet function measurement. To link this marker for clopidogrel response to adverse clinical outcome we designed the POPular study.

Original languageEnglish
Pages (from-to)22-24
Number of pages3
JournalNederlands Tijdschrift voor Klinische Chemie en Laboratoriumgeneeskunde
Volume37
Issue number1
Publication statusPublished - 1 Jan 2012

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