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Clopidogrel resistance and clopidogrel treatment failure

INTRODUCTION

Clopidogrel, a platelet P2Y12 receptor blocker (figure 1), is used with aspirin in patients who undergo coronary artery stenting or who have an acute coronary syndrome (ACS) to reduce the risk of subsequent cardiovascular events such as stent thrombosis or recurrent ACS. (See "Antiplatelet therapy for secondary prevention of stroke", section on 'Clopidogrel' and "Antiplatelet agents in acute non-ST elevation acute coronary syndromes", section on 'Clopidogrel' and "Antiplatelet therapy after coronary artery stenting", section on 'Information for patients' and "Antithrombotic therapy for percutaneous coronary intervention: General use", section on 'P2Y12 receptor blockers' and "Antiplatelet agents in acute ST elevation myocardial infarction", section on 'With primary PCI'.)

However, adverse cardiovascular events occur despite recommended dual antiplatelet therapy and this has been attributed in part to variable pharmacodynamic efficacy of one or both agents. Patients with "high on-treatment platelet reactivity” (HPR) have been labeled as being nonresponsive, hyporesponsive, or resistant. Numerous observational studies have demonstrated a strong link between HPR and recurrent ischemic events in stented patients [1,2]. Prospective evaluating personalized antiplatelet therapy based on platelet function testing has not demonstrated clinical benefit.

This topic will address whether there is a clinical role for screening for HPR as well as the management of patients who have clinical events on clopidogrel (clopidogrel treatment failure). The approach to such patients taking aspirin is presented separately. (See "Nonresponse and resistance to aspirin".)

DEFINITIONS

Resistance” or “nonresponsiveness” to an antiplatelet drug is a pharmacodynamic phenomenon where there is no significant (clinically important) change in platelet function after treatment as compared to the baseline. In studies employing light transmittance aggregometry, a change in maximal aggregation ≤10 percent from baseline, using adenosine diphosphate (ADP) as the agonist, is defined as “resistance.” “Resistance” has also been used interchangeably with “non-responsiveness” or “hypo-responsiveness” [3]. The degree of change from baseline in platelet function (responsiveness) has also been categorized into varies degrees. For example, “non-responsive” (≤10 percent), “hypo-responsive” (10 to 20 percent), and responsive (>20 percent).

Heightened platelet reactivity (HPR), also called high on-treatment platelet reactivity, to ADP during clopidogrel therapy indicates persistent response of the P2Y12 receptor (clopidogrel target). It is based on one measurement of on-treatment platelet reactivity. Usually, the cut points of HPR have been linked to clinical risk for thrombosis based on observational studies in stented patients.

                      

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Literature review current through: Sep 2014. | This topic last updated: Jun 13, 2014.
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