Body weight, CYP2C19, and P2Y12 receptor polymorphisms relate to clopidogrel resistance in a cohort of Chinese ischemic stroke patients with aspirin intolerance

Background: The ASA/AHA guidelines recommend a fixed dose of 90 mg of intravenous recombinant tissue plasminogen activator(rt-PA) for acute stroke patients weighing more than 100 kilograms(kg). Previous analyses in small studies have suggested that the magnitude of benefit with IV rt-PA is lower in patients with body weight >100 kg. We determined if body weight >100 kg(and receiving <0.9 mg/kg dose) independently influence patient clinical outcomes following IV rt-PA treatment. Methods: We pooled data from IV rt-PA treatment arms from 3 randomized controlled trials; NINDS IV rt-PA study, IMS-III and Albumin Treatment of Acute Ischemic Stroke(ALIAS part 1 and 2). Patients demographic, stroke severity, comorbidities, hospital outcome and 90-day modified Rankin Scale(mRS) were compared between patients >100 kg and those ≤100 kg body weight(defined by estimated weight). Multivariate logistic regression model was used to identify independent effect of >100 kg body weight on 90-day favorable outcome(defined as mRS 0-2). An ordinal analysis of the mRS was also performed. Results: Among 977 patients treated with IV rt-PA, total of 111 subjects had body weight >100 kg(11% of all patients). The mean age(±SD) for the patients with weight >100 Kg was significantly lower(60±11 versus 68±13, p<0.0001). The median admission NIHSS score was not different between the two groups(12 versus 13, p=0.08). Patients with weight >100 kg had higher rates of history of hypertension, diabetes mellitus, and hyperlipidemia. Patients with body weight >100 kg had longer period(days±SD) of hospitalization(11±14 versus 8±7, p=0.04). Compared with patients with ≤100 kg body weight, the rate of favorable outcome at 90 days was not significantly different among patients with >100 kg body weight[OR; (95% CI): 0.99 (0.91-1.04)p=0.91], after adjusting for potential confounders. The ordinal analysis did not showed any significant shift in the distribution of scores on the mRS in patients with >100 kg body weight(OR, 0.93; 95% CI, 0.64 to 1.37; P = 0.74). Conclusion: Body weight >100 kg(and receiving <0.9 mg/kg dose) did not reduce the benefit of IV rt-PA treatment in acute ischemic stroke patients. Our results support the current recommendations in the ASA/AHA guidelines.

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Fixed Dose IV rt-PA and Clinical Outcome in Ischemic Stroke Patients With Body Weight >100 kg: Pooled Data From 3 Randomized Clinical Trials

Journal of Stroke and Cerebrovascular Diseases ◽

10.1016/j.jstrokecerebrovasdis.2018.06.016 ◽

2018 ◽

Vol 27 (10) ◽

pp. 2843-2848

Author(s):

Shahram Majidi ◽

Christopher R. Leon Guerrero ◽

Kathleen M. Burger ◽

Dimitri Sigounas ◽

Wayne J. Olan ◽

...

Keyword(s):

Clinical Trials ◽

Body Weight ◽

Ischemic Stroke ◽

Clinical Outcome ◽

Randomized Clinical Trials ◽

Fixed Dose ◽

Stroke Patients ◽

Pooled Data

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Evaluation of Clopidogrel Resistance in Ischemic Stroke Patients

Internal Medicine ◽

10.2169/internalmedicine.50.3713 ◽

2011 ◽

Vol 50 (1) ◽

pp. 31-35 ◽

Cited By ~ 19

Author(s):

Takuya Fukuoka ◽

Daisuke Furuya ◽

Hidetaka Takeda ◽

Tomohisa Dembo ◽

Harumitu Nagoya ◽

...

Keyword(s):

Ischemic Stroke ◽

Stroke Patients ◽

Clopidogrel Resistance

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The Impact of Body Mass Index on the Thrombolytic Treatment of Acute Ischemic Stroke

Cerebrovascular Diseases ◽

10.1159/000446005 ◽

2016 ◽

Vol 42 (3-4) ◽

pp. 240-246 ◽

Cited By ~ 4

Author(s):

Anastasios Chatzikonstantinou ◽

Anne D. Ebert ◽

Marc E. Wolf

Keyword(s):

Body Mass Index ◽

Body Weight ◽

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Blood Volume ◽

Body Mass ◽

Intravenous Thrombolysis ◽

Normal Weight ◽

Thrombolytic Treatment ◽

Stroke Patients

Background: Body weight and body mass index (BMI) are regularly assessed factors in stroke patients for manifold reasons. However, their potential role specifically in intravenous thrombolysis has not been thoroughly examined. Methods: Data from 865 consecutive acute ischemic stroke patients treated with intravenous thrombolysis were analyzed. Patients were divided into different BMI categories (underweight, normal weight, overweight, obese) and compared based on the following factors: time window of treatment, clinical scores National Institute of Health Stroke Scale Score (NIHSS), modified Rankin scale (mRS) on admission and discharge, risk factors, stroke characteristics and thrombolysis complications. Recombinant tissue plasminogen activator (rtPA) doses relative to body weight and blood volume were also assessed. In a separate analysis, patients weighing up to 100 and >100 kg were compared. Results: Eighteen patients (2.1%) were underweight, 336 (38.8%) overweight, 194 (22.4%) obese and 317 (36.7%) had normal weight. Higher BMI category was associated with younger age, thrombolytic treatment later than 4.5 h, arterial hypertension, diabetes and higher relative rtPA dose relative to blood volume (p < 0.001). There were no significant differences concerning NIHSS and mRS scores or thrombolysis complications. Forty-six patients (5.3%) weighed over 100 kg. They were younger (p = 0.002) and treated later than patients under 100 kg (p < 0.001). Mean rtPA dose relative to body weight and to blood volume was significantly lower (0.7 vs. 0.9 mg/kg, p < 0.001 and 13 vs. 13.9 mg/l, p < 0.001). There was a marginal difference in NIHSS score improvement ≥4 points (26.1 vs. 40.2%, p = 0.038); otherwise, no outcome differences were found. Conclusion: BMI category does not significantly influence clinical outcome after thrombolysis. However, relevant NIHSS improvement was found more often in patients weighing up to 100 kg compared to those over 100 kg. Interestingly, patients with higher BMI or weight >100 kg were thrombolysed later than other patients.

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The role of platelet count and mean platelet volume in clopidogrel resistance in ischemic stroke patients

Journal of the Neurological Sciences ◽

10.1016/j.jns.2015.08.1454 ◽

2015 ◽

Vol 357 ◽

pp. e412 ◽

Cited By ~ 1

Author(s):

E. Xanmemmedov ◽

E. Coban ◽

B. Ciftci-Kavaklıoglu ◽

E. Acar ◽

F. Eren ◽

...

Keyword(s):

Platelet Count ◽

Ischemic Stroke ◽

Mean Platelet Volume ◽

Stroke Patients ◽

Platelet Volume ◽

Clopidogrel Resistance

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Clopidogrel Resistance in Patients With Stroke Recurrence Under Single or Dual Antiplatelet Treatment

Frontiers in Neurology ◽

10.3389/fneur.2021.652416 ◽

2021 ◽

Vol 12 ◽

Author(s):

Hyun Goo Kang ◽

Seung Jae Lee ◽

Sung Hyuk Heo ◽

Dae-il Chang ◽

Bum Joon Kim

Keyword(s):

Risk Factors ◽

Ischemic Stroke ◽

Multivariate Logistic Regression Analysis ◽

Stroke Recurrence ◽

Stroke Patients ◽

Antiplatelet Treatment ◽

Clopidogrel Resistance ◽

Factors Associated ◽

Artery Disease ◽

Dual Antiplatelet Treatment

Background: The factors associated with clopidogrel resistance in patients with stroke recurrence receiving single or dual antiplatelet treatment (SAPT or DAPT) may differ. This study compared the high on-treatment platelet reactivities (HPRs) and the factors associated with clopidogrel resistance in recurrent ischemic stroke patients receiving clopidogrel or aspirin and clopidogrel.Methods: We enrolled and allocated 275 recurrent ischemic stroke patients to the clopidogrel and DAPT groups and compared their demographics, conventional risk factors, and P2Y12 reaction units (PRUs). Clopidogrel resistance was categorized as PRU higher than 275. We performed a multivariate logistic regression analysis to determine the factors underlying clopidogrel resistance during SAPT and DAPT.Results: In total, 145 (52.7%) and 130 (47.3%) patients received clopidogrel and DAPT, respectively at recurrence. The risk factors of the two groups were not significantly different, except that coronary artery disease was more frequent in the DAPT group. The PRU was higher (255 ± 91 vs. 221 ± 84; p = 0.002) and clopidogrel resistance was more frequent (45.5 vs. 31.5%; p = 0.018) in the SAPT than in the DAPT group. Hyperlipidemia was associated with clopidogrel resistance during SAPT, and smoking (Odds ratio = 0.426, 95% confidence interval 0.210–0.861; p = 0.018) had a protective effect against clopidogrel resistance. For those receiving DAPT, old age, female, low hemoglobin A1c level, and high ARU were associated with clopidogrel resistance.Conclusions: HPR and clopidogrel resistance were more frequent in recurrent ischemic stroke patients receiving clopidogrel than in those receiving DAPT. Smoking was independently associated with less clopidogrel resistance among those receiving clopidogrel SAPT but not in those receiving DAPT.

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