Abstract W P355: Pathophysiologic, Rather than Pharmacologic Resistance Drives Aspirin Failure in Ischemic Stroke

Abstract

Background: Antiplatelet resistance is occurrence of thrombotic events while using antiplatelet agents. Apart from this clinical description, antiplatelet resistance can be defined by laboratory tests, which assess in vitro platelet reactivity against pharmacological challenges. The mechanisms underlying clinical and pharmacological antiplatelet resistance and their relationship with each other have not been evaluated extensively in patients with ischemic stroke. Furthermore, it is currently unclear whether these phenomena alter stroke phenotype, especially from the perspective of stroke severity and etiology. Methods: In-vitro aspirin resistance was evaluated using the VerifyNow® system within 48 hours of symptom onset in patients who had an ischemic stroke while using aspirin (n=99). Baseline characteristics (age, gender, risk factors, aspirin dose, other medications) and stroke features (clinical severity, DWI lesion volume, etiology) were compared between patients without resistance (defined as Aspirin Reaction Units, ARU<550), with resistance (ARU≥550) and an additional set of patients suffering from ischemic stroke while not using aspirin (n=314). Results: An ARU value≥550 was detected in 17 out of 99 patients who had ischemic stroke while using aspirin. Etiologies well known to be inadequately responsive to antiplatelet monotherapy, such as cardiac embolism and severe large artery atherosclerosis were present in 61% of aspirin users. Therefore, pharmacologic resistance by itself could be considered to be accountable for the ischemic event in only 7% of these patients. Stroke severity, lesion volume and baseline characteristics were not significantly different among patients with and without aspirin resistance. Patients without aspirin resistance were more likely to harbor a cardioembolic stroke etiology when compared to aspirin naive patients, even after adjustment for age and other cardiovascular risk factors (OR 2.3, 95%CI 1.4-4.1, p<0.01). Conclusion: Our findings highlight that pathophysiologic resistance, signifying the presence of etiologies that cannot be efficiently treated with aspirin treatment only, is the major contributor of clinical aspirin resistance observed in the setting of ischemic stroke.