Effect of Premedication Method and Drug Resistance of Antiplatelet Agent on Periprocedural Thromboembolic Events During Coil Embolization of an Unruptured Intracranial Aneurysm

Abstract

Objective : A retrospective review of premedication method and drug resistance of aspirin and clopidogrel in association with thromboembolic events during and after coil embolization of an unruptured intracranial aneurysm was conducted.Methods : Our premedication policy for coil embolization of an unruptured intracranial aneurysm has changed from administration of the loading dose before the procedure (i.e. loading group) to repeated administration of the maintenance dose for several days (i.e. preparation group). The loading group (27 patients with 29 aneurysms) and the preparation group (30 patients with 35 aneurysms) were compared for identification of the effect of premedication method on periprocedural thromboembolic events. The results of drug response assays of the preparation group were analyzed with respect to periprocedural thromboembolic events.Results : No statistically significant difference in incidence of thromboembolic events was observed between the loading group and the preparation group. Analysis of the results of the drug response assay showed high prevalence (56.7%, 73.3%) of clopidogrel resistance and relatively low prevalence (6.7%) of aspirin resistance. Patients who had thromboembolic events tended to have lower responsiveness to both aspirin and clopidogrel than patients without it.Conclusion : The method of antiplatelet premedication does not affect the rate of periprocedural thromboembolic events in coil embolization for treatment of an unruptured intracranial aneurysm. Nevertheless, considering the high prevalence of drug resistance, it is reasonable to premedicate antiplatelet agents in the preparation method for the drug response assay. Use of a higher dose of aspirin and clopidogrel or addition of an alternative drug (cilostazol or triflusal) can be applied against antiplatelet agent resistance. However, because the hemorrhagic risk associated with this supplementary use of antiplatelet agent has not been well-documented, the hemorrhagic risk and the preventive benefit must be weighed.

Antiplatelet therapy for prevention of thromboembolic complications in coiling-only procedures for unruptured brain aneurysms

“…Among these, 14 eligible studies (2486 patients) published between 2007 and 2018 were finally included (figure 1). 10–24…”

“…Five studies11 15 16 20 24 reported preprocedural platelet reactivity testing. All studies used the VerifyNow assay (Accumetrics, San Diego, California, USA) to measure the aspirin reaction units (ARU) and the P2Y12 reaction units (PRU).…”

“…Seven studies reported the incidence of silent infarcts on diffusion-MRI lesions (table 1). 11 15 17–21 None of these studies had a control arm. The incidence of silent infarcts with a single antiplatelet agent was 50.5% ‘96/190’ (95% CI 7.3% to 93.9%, I194.4%) vs 43.9% ‘196/446’ (95% CI 25.9% to 61.9%, I 1 73.4%) in patients receiving dual or multiple antiplatelet agents.…”

“…In the studies that reported the results of platelet reactivity testing (n=5), two studies20 24 modified the antiplatelet regimen by adding another antiplatelet agent, two studies15 16 did not report any treatment modification, and one study11 randomized patients into either continuing the same regimen or adding another antiplatelet agent (supplement table 3). The randomized trial described a significant reduction of thromboembolic complications with the modified (1.6%) versus the standard regimen (11.1%) 11.…”

“…The randomized trial described a significant reduction of thromboembolic complications with the modified (1.6%) versus the standard regimen (11.1%) 11. Of the remaining studies, one did not identify an association between high platelet reactivity and thromboembolic events,24 whereas the remaining studies either described an association of antiplatelet resistance with embolic events,15 or linked higher platelet reactivity to thromboembolic events or to multiple ischemic lesions on diffusion MRI but not with the prespecified resistance cut-off point 16 20…”