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

Abstract

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.

Relationship between Smoking and Responsiveness to Clopidogrel in Non-cardiogenic Ischemic Stroke Patients

“…In earlier studies, we measured platelet aggregation in non-cardiogenic ischemic stroke patients and found that 8-29% showed clopidogrel resistance (7,8). Various factors have been identified as causing individual variability in the antiplatelet effect of clopidogrel, including genetic polymorphism of cytochrome P450 (CYP) enzymes (9,10), and our group reported the involvement of chronic kidney disease (11). However, little is known regarding whether a relationship exists between smoking and the antiplatelet effect of clopidogrel in non-cardiogenic ischemic stroke patients.…”

Prestroke antiplatelet agents in first-ever ischemic stroke

“…Continued previous population-based study. 35,36 In cases of platelet responsiveness to aspirin, the degree of responsiveness can affect clinical outcome, stroke severity, and ischemic lesion volume. 35 Finally, we did not experimentally evaluate antiplatelet response (i.e., determine aspirin or clopidogrel resistance as a laboratory phenomenon through ex vivo tests).…”

Clopidogrel Response Variability in Unruptured Intracranial Aneurysm Patients Treated with Stent-Assisted Endovascular Coil Embolization : Is Follow-Up Clopidogrel Response Test Necessary?

“…Among affective factors correlated with clopidogrel response, the cytochrome P-450 enzyme was established to be the most important factor, correlated with genetic factors 2) . In addition, some studies have reported that drugs which are metabolized by the cytochrome P-450 enzyme, such as statins, PPIs, CCBs, β-blockers and/or SSRIs, affect clopidogrel response, as well as patient clinical factors such as DM, renal failure, and/or BMI 7 , 15 , 18 , 19 , 30) . In our study, pre-PRU and serum platelet count were important predictive factors, as in other studies 10) .…”

“…Clinical data consisted of age, sex, diabetes mellitus (DM) status, blood pressure, history of smoking, alcohol use, history of stroke, history of heart disease, and body mass index (BMI). Laboratory data consisted of glomerular filtration rate, platelet count, cholesterol levels, triglyceride levels, high-density lipoprotein levels, and low-density lipoprotein levels 7 , 15 , 18 , 21) . These factors were defined as follows : DM and hypertension (HTN) were defined by medical treatment after diagnosis, patients were considered smokers only if they currently smoked, alcoholism was defined as the consumption of more than 14 standard drinks per week or four drinks per day, history of stroke was determined by a previous cerebral infarction or intracranial hemorrhage, and history of heart disease included myocardial infarction, angina, valve disease, congenital heart disease, or previous heart operations.…”

“…In cardiology, many publications suggest that the variability of platelet response in patients treated with clopidogrel is correlated with the cytochrome P450 genotype, diabetes, and chronic kidney disease 2 , 15 , 28) . However, in the neuro-intervention literature, there is no established link between the variability of clopidogrel response and cerebral infarction.…”