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23-12-2009 | Cardiology | Article

Non-adherence partly explains clopidogrel ‘resistance’ in CAD, stroke


Free abstract

MedWire News: Non-adherence to clopidogrel can be reliably assessed through measurement of its inactive carboxyl metabolite (ICM), say researchers who found this biomarker correlated with inhibition of platelet aggregation (IPA).

The study, reported in the American Heart Journal, found a non-adherence rate of 22% in a large group of patients with coronary artery disease (CAD) and ischemic stroke.

“The data support the concept that it is not clopidogrel ‘resistance’ per se, but rather lack of adherence, at least in some patients may provoke additional acute vascular events including late stent thrombosis,” say Victor Serebruany (Johns Hopkins University, Towson, Maryland, USA) and colleagues.

Clopidogrel in combination with aspirin or as a monotherapy remains a “cornerstone of modern antiplatelet strategies,” say the researchers. But its efficacy has been questioned recently in light of studies showing substantial non-response or resistance.

To assess efficacy properly requires assurance that the drug has been administered, the researchers point out.

In the current study, they attempted to do this by measuring the derivates of clopidogrel metabolism – active thiol metabolite (ATM), ICM, and unchanged clopidogrel – in relation to IPA.

IPA was calculated by dividing post treatment platelet aggregation by baseline aggregation, expressed as a percentage.

Serebruany and team report that IPA was significantly, positively correlated with ATM , unchanged clopidogrel , and ICM.

Clopidogrel noncompliance was then defined as a plasma concentration of ICM <5000 ng/ml, since this was the most abundant marker.

The overall noncompliance rate was 22%, but was significantly higher in ischemic stroke survivors at 38% than in patients with CAD at 14%.

“The concept of routine measurements of clopidogrel metabolites should be applied not only as a useful research tool but also as a potential additional test to monitor compliance and potentially save lives,” Serebruany et al comment.

They also suggest that “future antiplatelet trials should recognize noncompliance as a critical confounding factor, and every attempt should be made to minimize and strictly monitor prescribed antiplatelet regimens.”

MedWire ( is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2009

By Andrew Czyzewski

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