MEDICATION / ANTIPLATELET THERAPY
Resistance to antiplatelet therapy
Created 01/12/2021, last revision 01/10/2022
- the definition ‘resistance to antiplatelet drugs should be limited to situations in which the failure of the drug to hit its pharmacological target has been documented by specific laboratory tests
- identification of patients with high residual platelet reactivity (HRPR) may be useful to predict their risk of atherothrombotic events
- the ideal laboratory test needs to be identified; clinical utility and cost-effectiveness are still unknown ⇒ monitoring of antiplatelet therapy should be considered for investigational purposes, it is not recommended in stroke prevention guidelines
Clinical resistance
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stroke recurrence despite the use of antiplatelet agents and good patient compliance
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laboratory tests may confirm a block of platelet function corresponding to the antiplatelet agent
- in such cases, always reconsider the possibility of different stroke etiology
- e.g., cardioembolism in paroxysmal atrial fibrillation (⇒ order repeated ECG Holter or long-term ECG monitoring)
- extensive atherosclerosis with embolization of calcified plaques
- advanced arteriolopathy
- vasculitis or non-inflammatory vasculopathy
“Laboratory” resistance
- the inability of antiplatelet agents to inhibit platelet function in a specific manner
- CLP – inability to effectively block P2Y12 receptors
- ASA – inability to inhibit platelet function in a TXA2-dependent manner
- instead of resistance, the term HPR (High on-treatment Platelet Reactivity) or HRPR (high residual platelet reactivity) is also used [Garabedian, 2013] [Cattaneo, 2013]
- according to meta-analyses, resistance is present in up to 30% of cases; these patients have a higher risk of recurrent stroke/TIA
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Testing of resistance
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Aspirin resistance
- laboratory resistance = inability of aspirin to reduce TXA2 production (COX-1 dependent) and subsequently inhibit TXA2-dependent platelet function
Variable response to aspirin may be due to these factors:
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Clinical
Cellular
Genetic
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- a meta-analysis of 20 trials (prospectively followed 2930 patients with CVD) showed a higher risk of CV events in patients with aspirin resistance, regardless of the method used. Aspirin resistance was detected in 28% of patients. However, the meta-analysis did not demonstrate a clinical effect of add-on antiplatelet therapy in aspirin-resistant patients [Krasopoulos, 2008]
- aspirin resistance seems to be associated with a more severe neurological deficit (higher NIHSS) and greater infarct size in acute stroke patients [Zheng, 2013]
Clopidogrel resistance
- the problem with resistance or variable sensitivity also applies to clopidogrel
- CLP resistance is defined as the inability to block P2Y12 receptors effectively
- it often occurs in patients who have aspirin resistance as well
- according to meta-analysis, the prevalence is 27-35%, and patients with resistance have a higher risk of recurrent stroke/TIA even on dual antiplatelet therapy (subanalyses of SPS3, CHANCE, and other trials) [Wang, 2016] [Hernandez-Suarez, 2017]
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