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Clopidogrel resistance and clopidogrel treatment failure

Udaya S Tantry, PhD
Charles H Hennekens, MD, DrPH
James L Zehnder, MD
Paul A Gurbel, MD
Section Editors
Lawrence LK Leung, MD
Donald Cutlip, MD
Deputy Editor
Gordon M Saperia, MD, FACC


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 ST elevation myocardial infarction", section on 'With primary PCI' and "Antithrombotic therapy for elective percutaneous coronary intervention: General use", section on 'P2Y12 receptor blockers' and "Antiplatelet agents in acute non-ST elevation acute coronary syndromes" and "Long-term antiplatelet therapy after coronary artery stenting in stable patients", section on 'Information for patients'.)

Nonetheless, as is the case for any intervention of life-saving benefit, adverse cardiovascular events occur despite recommended dual antiplatelet therapy. This has been hypothesized to be attributable, 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]. The totality of evidence to support prospective evaluation of personalized antiplatelet therapy based on platelet function is neither consistent nor complete.

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".)

The role of screening for HPR in patients treated with either prasugrel or ticagrelor has not been adequately evaluated. Relevant studies will be presented.


"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 inappropriately 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).

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Literature review current through: Nov 2017. | This topic last updated: Nov 02, 2016.
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