Evaluation of Clopidogrel Resistance in Ischemic Stroke Patients

Fukuoka, Tatsunari; Furuya, Daisuke; Takeda, Hidetaka; Dembo, Tomohisa; Nagoya, Harumitsu; Kato, Yukio; Deguchi, Ichiro; Maruyama, Haruhiko; Horiuchi, Yohsuke; Tanahashi, Norio

doi:10.2169/internalmedicine.50.3713

Cited by 27 publications

(16 citation statements)

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“…Lee et al reported that the rate of clopidogrel resistance defined as a % inhibition <40% was 42.9% (13). The rate of clopidogrel resistance using 20 μM ADP and <20% inhibition was 29% in the present study, which was higher than our previous findings (8-18%) using turbidimetry, 1-4 μM ADP and screen filtration pressure (7). The frequency of clopidogrel resistance was dependent upon the cut-off point or type of measurement method used.…”

Section: Discussioncontrasting

confidence: 80%

“…Recently, much attention has been paid to clopidogrel resistance (1-6), however, there are few reports of clopidogrel resistance in ischemic stroke patients. Using a turbidimetric method with a low dose of ADP (1-4 μM) and screen filtration pressure, we determined that the rate of clopidogrel resistance in patients with ischemic stroke is 8-18% (7).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2011

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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.

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Section: Discussioncontrasting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

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

et al. 2011

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“…The relatively limited, available literature indicates that the prevalence of HTPR in CVD varies between 3-62% with aspirin monotherapy [40,65], 8-61% with clopidogrel monotherapy [46,49,77] and 56-59% when dipyridamole is added to aspirin [27] in the early, subacute or late phases after TIA/stroke onset. These summary figures for clopidogrel-HTPR exclude data from two studies that confirmed that the standard C-ADP cartridge on the PFA-100 is not sensitive at detecting the antiplatelet effects of clopidogrel if one uses a cross-sectional, case-control definition of HTPR [28,37].…”

Section: Discussionmentioning

confidence: 99%

“…Ex vivo HTPR was evaluated with optical aggregometry in PRP in 72 patients within 7-62 days of non-cardioembolic TIA/ ischaemic stroke who were on 75 mg of clopidogrel daily for !1 week [49]. Clopidogrel-HTPR was seen in 8.3% with 1 mmol/L ADP and 18.1% with 4 mmol/L ADP.…”

Section: Platelet Aggregometrymentioning

confidence: 91%

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

et al. 2015

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The majority of patients with ischaemic cerebrovascular disease (CVD) are not protected from further vascular events with antiplatelet therapy. Measurement of inhibition of platelet function ex vivo on antiplatelet therapy, using laboratory tests that correlate with the clinical effectiveness of these agents, would potentially enable physicians to tailor antiplatelet therapy to suit individuals. A systematic review of the literature was performed to collate all available data on ex vivo platelet function/reactivity in CVD patients, especially those treated with aspirin, dipyridamole or clopidogrel. Particular emphasis was paid to information from commonly available whole blood platelet function analysers (PFA-100 Õ , VerifyNow Õ and Multiplate Õ ). Data on pharmacogenetic mechanisms potentially influencing high on-treatment platelet reactivity (HTPR) on antiplatelet therapy in CVD were reviewed. Two-hundred forty-nine potentially relevant articles were identified; 93 manuscripts met criteria for inclusion. The prevalence of ex vivo HTPR in CVD varies between 3-62% with aspirin monotherapy, 8-61% with clopidogrel monotherapy and 56-59% when dipyridamole is added to aspirin in the early, subacute or late phases after TIA/stroke onset. The prevalence of HTPR on aspirin was higher on the PFA-100 than on the VerifyNow in one study (p50.001). Furthermore, the prevalence of HTPR on aspirin was lower when one used 'novel longitudinal' rather than 'cross-sectional, case-control' definitions of HTPR on the PFA early after TIA or stroke (p ¼ 0.003; 1 study). Studies assessing the influence of genetic polymorphisms on HTPR in CVD patients are limited, and need validation in large multicentre studies. Available data illustrate that an important proportion of CVD patients have ex vivo HTPR on their prescribed antiplatelet regimen, and that the prevalence varies depending on the definition and assay used. Large, adequately-sized, prospective multicentre collaborative studies are urgently needed to determine whether comprehensive assessment of HTPR at high and low shear stress with a range of user-friendly whole blood platelet function testing platforms, in conjunction with pharmacogenetic data, improves our ability to predict the risk of recurrent vascular events in CVD patients, and thus enhance secondary prevention following TIA or ischaemic stroke.

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“…In Japan, the administration of aspirin, clopidogrel and/or cilostazol is recommended to prevent the recurrence of noncardiogenic ischemic stroke. We previously measured the degree of platelet aggregation in noncardiogenic ischemic stroke patients and reported that 8-29% of the patients had clopidogrel resistance (7)(8)(9). Several factors, including genetic polymorphisms of the drug-metabolizing enzyme CYP2C19, have been identified as causes of clopidogrel resistance (10,11).…”

Section: Introductionmentioning

confidence: 99%

Response to Clopidogrel and Its Association with Chronic Kidney Disease in Noncardiogenic Ischemic Stroke Patients

et al. 2014

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Objective Noncardiogenic ischemic stroke patients with chronic kidney disease (CKD) are known to have a greater rate of ischemic stroke recurrence than those without. Although clopidogrel is often used to prevent the recurrence of noncardiogenic ischemic stroke, the relationship between the response to clopidogrel and CKD is unclear. In the present study, the relationship between the response to clopidogrel and the presence of CKD was investigated in noncardiogenic ischemic stroke patients. Methods A total of 129 noncardiogenic ischemic stroke patients receiving 75 mg/day of clopidogrel for ! 1 week were evaluated. The VerifyNow P2Y12 Assay was used to measure the level of platelet aggregation induced by 20 μM of adenosine diphosphate, and the degree of platelet aggregation and frequency of clopidogrel resistance were compared between 34 patients with CKD and 95 patients without CKD. Clopidogrel resistance was defined as a P2Y12 Reaction Units (PRU) value of >230 and/or % inhibition <20%. Results The PRU value was 201.9±91.3 in the patients with CKD and 163.3±86.4 in the patients without CKD (p=0.035). The frequency of a PRU value of >230 was 44.1% (15 patients) among the patients with CKD and 17.9% (17 patients) among those without CKD (p=0.002). The percent inhibition was 29.9%± 28.1% among the patients with CKD and 41.1%±28.0% among the patients without CKD (p=0.030). The frequency of % inhibition <20% was 47.1% (16 patients) among the patients with CKD and 26.3% (25 patients) among those without CKD (p=0.026). Conclusion The present study showed that noncardiogenic ischemic stroke patients with CKD have a greater frequency of clopidogrel resistance, thus suggesting that the response to clopidogrel is diminished in these patients.

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Evaluation of Clopidogrel Resistance in Ischemic Stroke Patients

Cited by 27 publications

References 9 publications

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

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

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

Response to Clopidogrel and Its Association with Chronic Kidney Disease in Noncardiogenic Ischemic Stroke Patients

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