Platelet inhibition by adjunctive cilostazol suppresses the frequency of cerebral ischemic lesions after carotid artery stenting in patients with carotid artery stenosis

Abstract

Objective: Optimal platelet inhibition is an important therapeutic adjunct in patients with carotid artery stenosis undergoing carotid artery stenting (CAS). Clopidogrel resistance is associated with increased periprocedural thromboembolic complications from neurovascular stent placement procedures. The addition of cilostazol to dual antiplatelet therapy (DAT) has been reported to reduce platelet reactivity and to improve clinical outcomes after percutaneous coronary intervention. This study was undertaken to evaluate the impact of adjunctive cilostazol in patients with CAS. Methods: Platelet function was assessed by light transmittance aggregometry using the VerifyNow assay. Sixty-four consecutive patients who underwent CAS received standard DAT, clopidogrel (75 mg daily), and aspirin (100 mg daily) more than 4 weeks before the procedure. From 2010 to 2011 (period I), 28 patients underwent CAS under standard DAT. From 2011 to 2013 (period II), 36 patients prospectively had preoperative assessment of platelet function, and 13 patients with clopidogrel resistance received adjunctive cilostazol (200 mg daily) in addition to standard DAT. The incidence of new ipsilateral ischemic lesions on diffusion-weighted imaging a day after CAS and ischemic or hemorrhagic events within 30 days was assessed. Results: Clopidogrel resistance was indentified in 12 patients (43%) in period I and 13 patients (36%) in period II (P [ .615). In period II, the addition of cilostazol significantly decreased P2Y12 reaction units and % inhibition (P [ .006 and P [ .005, respectively), and there was a significant difference in P2Y12 reaction units between the two periods. New ipsilateral ischemic lesions were significantly decreased in period II (2/36 patients) compared with period I (7/28 patients; P [ .034); however, there was no significant difference in hemorrhagic and thromboembolic events between the two periods. Conclusions: Adjunctive cilostazol (triple antiplatelet therapy) in clopidogrel-resistant patients reduces the rate of clopidogrel resistance and suppresses new ischemic lesions without hemorrhagic complications, as compared with standard DAT. Antiplatelet management based on the evaluation of antiplatelet resistance would be required for prevention of perioperative thromboembolic complications in CAS. (J Vasc Surg 2014;59:761-7.) From the Departments of Neurosurgery a and Radiology, b Nara Medical University.

Meta-Analysis of Studies Evaluating the Effect of Cilostazol on Major Outcomes After Carotid Stenting

“…Regarding major/minor bleeding, 3 of the studies 17,20,21 did not report any result and 2 studies 16,22 reported null bleeding events after CAS. Only one study 19 reported 7 bleedings overall (6 access site hematomas and 1 hemorrhage due to Regarding the revascularization rate post ISR, only 3 studies 18,19,22 reported a pooled rate of 33 endovascular treatments in 51 cases of ISR (65%) without stratifying the results according to antiplatelet treatment.…”

Clinical Significance of Acute and Serial Platelet Function Testing in Acute Ischemic Stroke

“…Despite aspirin administration for 5 consecutive days after acute ischemic stroke, 27% of patients with HAPR at the time of the aARU measurement had persistent HAPR at the time of the ARU‐5 measurement. Previous studies found that adding other antiplatelet therapies to aspirin therapy was associated with a decrease in the rate of antiplatelet resistance in antiplatelet therapy‐resistant patients and had beneficial effects on the risks of ischemic events; however, there were other studies with conflicting results . Given that the frequency of combination antiplatelet therapy was higher in patients with NAPR than in patients with HAPR at the time of the ARU‐5 measurement, patients with HAPR at the time of the acute platelet function test may be candidates for additional antiplatelet therapies.…”

Evaluation and Management of In-stent Low-density Area on CTA after Carotid Artery Stenting at Subacute Phase

“…21,22) Furthermore, a study indicated that additional administration of cilostazol in clopidogrelresistant patients reduced platelet aggregation, significantly decreasing the incidence of new ischemic lesions on DWIs after CAS. 23) In the present study, triple antiplatelet therapy was administered in the perioperative phase, which might have significantly inhibited thrombus formation even with the appearance of LDA after CAS, contributing to the absence of symptomatic lesions. However, platelet aggregation monitoring was not conducted, and the relationship between platelet aggregation and LDA formation should be investigated in future studies.…”