Evolving Approaches to Antithrombotics in Stroke Prevention and Treatment

Vijayakumar Javalkar, MD, MCh; Okkes Kuybu, MD; Abdallah Amireh, MD; Roger E. Kelley, MD


South Med J. 2020;113(11):585-592. 

In This Article

Antiplatelet Resistance

Aspirin Resistance

Clinical aspirin resistance is identified when a patient develops ischemic events despite actually taking aspirin.[30] In a meta-analysis, the mean prevalence of aspirin resistance was 24%.[31] Approximately 10% to 20% of aspirin-treated patients experience a recurrent vascular event within 5 years,[32] with various causes identified.[33] Of relevance, in this regard, the only Food and Drug Administration–approved test for evaluating aspirin resistance involves measuring the biomarker 11-dehydro-thromboxane B2 in the urine.[34] In one study, urinary concentration of this biomarker was a strong independent risk factor for all-cause mortality among patients with stable coronary artery disease (CAD) on aspirin therapy;[33] however, it is not established that altering therapy in affected patients would reduce ischemic events.[35]

Clopidogrel Resistance

The reported prevalence of clopidogrel resistance varies from 16% to 50%.[36] Clopidogrel is a pro-drug and requires activation via the cytochrome P450 CYP2C19 pathway for antiplatelet activity. The genome of certain individuals contains CYP2C19 loss of function alleles, which are associated with reduced platelet response to clopidogrel.[37] Various methods, such as light transmission aggregometry, multiple electrode aggregometry, and point-of-care commercially available products, may be used to measure platelet reactivity. Such methodologies have been used to determine clopidogrel responsiveness clinically.[38] The measurement of vasodilator-stimulated phosphoprotein phosphorylation analysis, for example, has been reported to accurately detect biological clopidogrel resistance.[39] There appears to be some potential clinical value with such methods. In the GRAVITAS study,[40] the determination of the achievement of adequate clopidogrel response via an adenosine diphosphate–induced platelet agglutination measurement was associated with a lower risk of cardiovascular events following PCI.

Other potential limitations of clopidogrel include drug–drug interactions with proton pump inhibitor agents which are reported to reduce the efficacy of clopdiogrel.[41] A number of reports have associated the occurrence of post-PCI ischemic events with clopidogrel nonresponsiveness.[42]