Clopidogrel Resistance and the Effect of Combination Cilostazol in Patients with Ischemic Stroke or Carotid Artery Stenting Using the VerifyNow P2Y12 Assay

Abstract

Objective The inhibitory response to clopidogrel considerably varies among individuals and clopidogrel resistance is a risk factor for thrombotic events in patients with cardiovascular disease. Based on the platelet aggregation evaluated by the VerifyNow P2Y12 Assay, the present study investigated clopidogrel resistance and the effect of cilostazol addition. Methods We measured the ability of 20 μM ADP to aggregate platelets using the VerifyNow P2Y12 Assay. Clopidogrel resistance was defined as % inhibition of <20% in this assay. Patients We examined 77 patients (53 men and 24 women, aged 65.8±9.9 years) with ischemic stroke or carotid artery stenting who received clopidogrel (75 mg) for >7 days at our hospital between October 2009 and March 2010. For 62 patients (42 men and 20 women, aged 65.3±9.9 years) 75 mg clopidogrel alone was administered (clopidogrel only group); the other 15 patients (11 men and 4 women, aged 67.9±9.9 years) received 75 mg of clopidogrel plus 100 or 200 mg of cilostazol (cilostazol combination group). Results Clopidogrel resistance was identified in 18 (29%) of the 62 patients in the clopidogrel only group. The percent inhibition was significantly higher in the cilostazol combination group than in the clopidogrel only group (41.7±28.0% vs. 64.9±22.7%, p=0.005). None of the patients in the cilostazol combination group had % inhibition of <20%. Conclusion Clopidogrel resistance developed in 29% of patients given clopidogrel alone. The addition of cilostazol to clopidogrel may have intensified platelet inhibition.

Platelet function testing in transient ischaemic attack and ischaemic stroke: A comprehensive systematic review of the literature

“…The prevalence of aspirin-HTPR on the VerifyNow in this study was similar to other studies in the early phase after stroke [73]. The prevalence of clopidogrel-HTPR was higher than that reported in the early phase after stroke [74], but similar to another study in late phase CVD patients. [37] Jover et al assessed clopidogrel-HTPR in 18 TIA/stroke patients with the VerifyNow P2Y12 assay, INNOVANCE Õ PFA P2Y cartridge, 5 mmol/l ADP-induced optical aggregometry and vasodilatorstimulated phosphoprotein 7 and 90 days after commencing clopidogrel 75 mg daily as monotherapy or in combination with aspirin 100-300 mg daily [77].…”

“…Further studies identified aspirin-HTPR in 21% of patients on 100-200 mg of aspirin monotherapy41 week after TIA/ischaemic stroke onset [73], and clopidogrel-HTPR in 29% on 75 mg of clopidogrel daily within 1 week of TIA/ischaemic stroke with the VerifyNow [74].…”

Association between Postprocedural Infarction and Antiplatelet Drug Resistance after Coiling for Unruptured Intracranial Aneurysms

“…An abnormal antiplatelet response was defined as Ͼ550 aspirin response units (ARUs) and/or Ͼ240 P2Y12 receptor reaction units (PRUs). 15,16 Also, we tried to investigate and clarify the optimal cutoff values of both ARUs and PRUs that were associated with DPL, which have been controversial in the literature.…”

Formulation of Solid Dosage Form Containing Clopidogrel and Cilostazol and Its HPLC Analysis

“…Also, resistance to clopidogrel is a major risk factor for thrombotic events in patients with cardiovascular disease conditions. In a study carried out by Maruyama H. et al, evaluated by the VerifyNow P2Y12 assay, the effect of the addition of cilostazol on clopidogrel resistance was investigated [4]. Of the 72 patients in the study, 15 patients who received 75 mg of clopidogrel in addition to 100/200 mg of cilostazol, platelet inhibition was intensified; thereby suggesting that the addition of cilostazol may proves to be efficious in the treatment of patients with ischemic stroke and other CVD.…”