Clopidogrel resistance: myth or reality

The efficacy of clopidogrel, as an established anti-platelet agent for the acute coronary syndrome treatment and for the thrombotic complications prevention after percutaneous coronary angioplasty and coronary artery stenting has been supported by the evidence of several major randomized clinical trials. However, some patients treated with clopidogrel have a minor, but still a risk of coronary artery thrombosis and sudden death. Moreover, clopidogrel was not effective in patients after ischemic stroke, as well as it was not effective for the primary prevention of vascular events. Several authors proposed the theory of " clopidogrel-resistance " . However, this theory is based on a limited number of laboratory findings, and was not supported by the evidence of clinical studies. The phenomena of " clopidogrel-resistance " could be masked by the low patient compliance, while the rate of such patients could exceed 30% after one year of treatment. The offered methods for overcoming clopidogrel-resistance include doubling or tripling of the loading dose (600-900 mg vs. 300mg) or administration one or two more potent antiplatelet agents. However, such approach could not only increase the risk of major and fatal bleedings, but could have a potential to reduce patients compliance, and consequently increase the risk of thrombosis. Only multicenter randomized study with hard outcome or ideally survival endpoint, supported by comprehensive serial platelet assessment, strict compliance rules including measurement of clopidogrel metabolite(s) will determine whether " clopidogrel resistance " is a real danger (as suggested by the platelet biomarkers), or an artificial tool (as suggested by the randomized clinical evidence) introduced to help novel antiplatelet agents to gain the vascular market share.


Kardiologiia. 2007;47(10):69-72

[Article in Russian]


Serebriany VL, Malinin AI, Makarov LM.
D. Hopkins University, Baltimore, USA.