The Phenomenon of Clopidogrel High On-Treatment Platelet Reactivity in Ischemic Stroke Subjects: A Comprehensive Review

Abstract

Clopidogrel is increasingly being used for the secondary prevention of ischemic stroke according to the updated guidelines on acute stroke management. Failure to achieve a drug response is referred to as clopidogrel resistance. Similarly, a higher activation of platelets during clopidogrel therapy—high on-treatment platelet reactivity—is equivalent to a reduced effectiveness of a therapy. Clopidogrel resistance is considered to be a common and multifactorial phenomenon that significantly limits the efficacy of antiplatelet agents. The aim of the current study is to review the latest literature data to identify the prevalance and predictors of clopidogrel high on-treatment platelet reactivity among stroke subjects and to establish the potential impact on clinical outcomes and prognosis. Clinical databases were searched by two independent researchers to select relevant papers on the topic, including all types of articles. Several important predictors contributing to clopidogrel resistance were identified, including genetic polymorphisms, the concomitant use of other drugs, or vascular risk factors, in particular nonsmoking and diabetes. Clopidogrel high on-treatment platelet reactivity has a negative impact on the clinical course of stroke, worsens the early- and long-term prognoses, and increases the risk of recurrent vascular events. Platelet function testing should be considered in selected stroke individuals, especially those predisposed to clopidogrel resistance, for whom an improvement in the efficacy of antiplatelet therapy is essential. This particular group may become the greatest beneficiaries of the modification of existing therapy based on platelet function monitoring.

A Pharmacogenetic Study of CYP2C19 in Acute Coronary Syndrome Patients of Colombian Origin Reveals New Polymorphisms Potentially Related to Clopidogrel Therapy

“…To date, association studies between genetic variants, cardiovascular events, HPR and LPR have focused on polymorphisms on PON1 (p.Q192R), ABCB1 (C.3435C>T) polymorphisms, and particularly the CYP2C19 gene [ 12 , 13 , 14 , 15 ]. CYP2C19, an enzyme of the cytochrome P450 (CYP450) superfamily, is considered the key enzyme related to the bioactivation of clopidogrel through the two-step oxidative process that leads to the formation of 2-oxo-clopidogrel and the active metabolite clopi-H4 [ 16 , 17 ]. Only some genetic variants of CYP2C19 have been widely explored and their relation to the therapeutic response to clopidogrel has been established.…”

Hypercoagulability as Measured by Thrombelastography May Be Associated with the Size of Acute Ischemic Infarct—A Pilot Study

“…Hypercoagulability still remains the baseline background of a higher risk of cerebrovascular events, incluing ischemic stroke [ 3 , 4 ]. Many studies have shown that high platelet reactivity, higher levels of fibrinogen or hyperactivated properties of the coagulation system may correspond to the increased incidence of recurrent vascular events [ 5 , 6 ]. Therefore, TEG ® is widely applicated in the evaluation of clot transformation and monitoring the coagulation properties of blood in different branches of medicine [ 7 , 8 , 9 , 10 , 11 ].…”

Unfavorable Dynamics of Platelet Reactivity during Clopidogrel Treatment Predict Severe Course and Poor Clinical Outcome of Ischemic Stroke

“…The clinical significance of a similar phenomenon in relation to clopidogrel is also increasingly being raised. Considering that the mechanisms and background of the low responsiveness to clopidogrel are similar to those of aspirin, analogous and comparable clinical consequences should also be expected [ 12 ]. Other authors investigated the impact of clopidogrel resistance on the clinical course of stroke and reported that it is associated with worse clinical conditions and poor early and late prognosis [ 13 , 14 , 15 , 16 , 17 ].…”