Application of Age, Body Mass Index, Chronic Kidney Disease, Diabetes, and Genotyping Score for Efficacy of Clopidogrel: Secondary Analysis of the CHANCE Trial

Stroke ◽  
2021 ◽  
Author(s):  
Liye Dai ◽  
Jie Xu ◽  
Hongyi Yan ◽  
Zimo Chen ◽  
Yuesong Pan ◽  
...  

Background and Purpose: The age, body mass index, chronic kidney disease, diabetes, and genotyping (ABCD-GENE) score is a validated risk score integrating CYP2C19 genotypes with clinical risk factors influencing clopidogrel response that would allow the more precise identification of subjects at risk for high platelet reactivity and adverse clinical outcomes. Our objective was to further verify application of the ABCD-GENE score and investigate appropriate cutoff value in patients with minor stroke or transient ischemic attack. Methods: In this post-analysis of the CHANCE trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events), the ABCD-GENE score was calculated for all patients enrolled in this study. By using the proposed cutoff of 10, patients were stratified as being at high risk for high platelet reactivity or not. We further categorized the ABCD-GENE score to 0 to 5, 6 to 24, and >24 to investigate the cutoff value of this scale in clinical application. Stroke recurrence at 3 months was considered as the primary outcome. Results: Among a total of 2923 patients with minor stroke/transient ischemic attack, there were 2273 (77.76%) with ABCD-GENE score <10 and 650 (22.24%) patients with ABCD-GENE score ≥10. Compared with the aspirin alone, hazard ratios (95% CIs) of the clopidogrel-aspirin therapy for stroke recurrence were 0.70 (0.54–0.91) and 0.76 (0.46–1.24), among patients of ABCD-GENE scores <10 and ABCD-GENE scores ≥10, respectively. Stratified analyses by ABCD-GENE score 0 to 5, 6 to 24, and >24, hazard ratios of the clopidogrel-aspirin therapy for stroke recurrence were 0.57 (95% CI, 0.38–0.85), 0.78 (0.58–1.06), and 1.20 (0.44–3.28) ( P value for trend=0.0052). Conclusions: Among Chinese minor stroke/transient ischemic attack population, the efficacy of clopidogrel-aspirin therapy was decreased in patients with higher ABCD-GENE score. Our study suggests that CYP2C19 genotypes and clinical risk factors can be integrated by ABCD-GENE score to estimate the efficacy of clopidogrel-aspirin therapy.

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Shinichiro Uchiyama ◽  
Takao Hoshino ◽  
Hugo Charles ◽  
Kenji Kamiyama ◽  
Taizen Nakase ◽  
...  

Background: We have reported 5-year risk of stroke and vascular events after a transient ischemic attack (TIA) or minor ischemic stroke in patients enrolled into the TIAregistry.org, which was an international multicenter-cooperative, prospective registry (N Engl J Med 2018;378:2182-90). We conducted subanalysis on the 5-year follow-up data of Japanese patients in comparison with non-Japanese patients. Methods: The patients were classified into two groups on ethnicity, Japanese (n=345) and non-Japanese (n=3502), and their 5-year event rates were compared. We also determined predictors of five-year stroke in both groups. Results: Death from vascular cause (0.9% vs 2.7%, HR 0.28, 95% CI 0.09-0.89, p=0.031) and death from any cause (7.8% vs 9.9%, HR 0.67, 95% CI 0.45-0.99, p=0.045) were fewer in Japanese patients than in non-Japanese patients, while stroke (13.9% vs 7.2%, HR 1.78, 95% CI 1.31-2.43, p<0.001) and intracranial hemorrhage (3.2% vs 0.8%, HR 3.61. 95% CI 1.78-7.30, p<0.001) were more common in Japanese than non-Japanese patients during five-year follow-up period. Caplan-Meyer curves at five-years showed that the rates of stroke was also significantly higher in Japanese than non-Japanese patients (log-rank test, p=0.001). Predictors for stroke recurrence at five years were large artery atherosclerosis (HR 1.81, 95% CI 1.31-2.52, p<0.001), cardioembolism (HR 1.71, 95% CI 1.18-2.47, p=0.004), multiple acute infarction (HR 1.77, 95% CI 1.27-2.45, p<0.001) and ABCD 2 score 6 or 7 (HR 1.96, 95% CI 1.38-2.78, p<0.001) in non-Japanese patients, although only large artery atherosclerosis (HR 3.28, 95% CI 1.13-9.54, p=0.029) was a predictor for stroke recurrence in Japanese patients. Conclusions: Recurrence of stroke and intracranial hemorrhage were more prevalent in Japanese than non-Japanese patients. Large artery atherosclerosis was a predictor for stroke recurrence not only in non-Japanese patients but also in Japanese patients.


Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Joon Hwa Lee ◽  
Hyunjin Jo ◽  
Jihoon Cha ◽  
Woo-Keun Seo ◽  
Oh Young Bang ◽  
...  

Background and purpose: We aimed to investigate the role of perfusion MRI parameters (TTP: time to peak, CBF: cerebral blood flow, CBV: cerebral blood volume) as a prognostic factor for the risk of stroke recurrence or cardiovascular outcome in patients with transient ischemic attack (TIA) or minor stroke. Methods: We retrospectively reviewed TIA or minor stroke patients who underwent our stroke MRI protocol (DWI, perfusion MRI, and MRA) in a consecutively collected stroke registry. Primary outcome was nonfatal stroke recurrence and secondary outcome was cardiovascular composite outcome. Multivariate analysis was used to examine the association of perfusion MRI parameters and angiographic findings with the risk of stroke recurrence and cardiovascular event. Results: Of the 326 patients who met inclusion criteria, we identified 15(4.6%) nonfatal strokes and 25(7.7%) cardiovascular composite events during the first 1 year after the index TIA or minor stroke. The presence of regional delayed perfusion on TTP maps (p=0.002) and regional hyperperfusion on CBV maps (p<0.001) were associated with recurrent stroke. In MRA images, concomitant stenosis of the intracranial arteries and/or extracranial carotid arteries was associated with cardiovascular events (p=0.009). Using multivariate cox proportional hazard analysis, presence of regional hyperperfusion on CBV remained an independent predictor of recurrent stroke (HR 10.82, 95% CI 4.19-38.67, p<0.001) and cardiovascular event (HR 6.30, 95% CI 2.67-18.25, p<0.001). The AUC of the CBV maps was also greater than other parameters for the prediction of stroke recurrence (AUC=0.701, 95% CI 0.54-0.86) and cardiovascular composite outcome (AUC=0.628, 95% CI 0.50-0.76). Conclusions: Increased CBV on perfusion MRI, representing the hemodynamic status of postischemic hyperperfusion, could be more useful than other perfusion parameters in predicting poor prognosis of TIA or minor stroke patients.


2021 ◽  
Vol 12 ◽  
Author(s):  
Shinya Tomari ◽  
Christopher R. Levi ◽  
Elizabeth Holliday ◽  
Daniel Lasserson ◽  
Jose M. Valderas ◽  
...  

Background: One-year risk of stroke in transient ischemic attack and minor stroke (TIAMS) managed in secondary care settings has been reported as 5–8%. However, evidence for the outcomes of TIAMS in community care settings is limited.Methods: The INternational comparison of Systems of care and patient outcomes In minor Stroke and TIA (INSIST) study was a prospective inception cohort community-based study of patients of 16 general practices in the Hunter–Manning region (New South Wales, Australia). Possible-TIAMS patients were recruited from 2012 to 2016 and followed-up for 12 months post-index event. Adjudication as TIAMS or TIAMS-mimics was by an expert panel. We established 7-days, 90-days, and 1-year risk of stroke, TIA, myocardial infarction (MI), coronary or carotid revascularization procedure and death; and medications use at 24 h post-index event.Results: Of 613 participants (mean age; 70 ± 12 years), 298 (49%) were adjudicated as TIAMS. TIAMS-group participants had ischemic strokes at 7-days, 90-days, and 1-year, at Kaplan-Meier (KM) rates of 1% (95% confidence interval; 0.3, 3.1), 2.1% (0.9, 4.6), and 3.2% (1.7, 6.1), respectively, compared to 0.3, 0.3, and 0.6% of TIAMS-mimic-group participants. At one year, TIAMS-group-participants had twenty-five TIA events (KM rate: 8.8%), two MI events (0.6%), four coronary revascularizations (1.5%), eleven carotid revascularizations (3.9%), and three deaths (1.1%), compared to 1.6, 0.6, 1.0, 0.3, and 0.6% of TIAMS-mimic-group participants. Of 167 TIAMS-group participants who commenced or received enhanced therapies, 95 (57%) were treated within 24 h post-index event. For TIAMS-group participants who commenced or received enhanced therapies, time from symptom onset to treatment was median 9.5 h [IQR 1.8–89.9].Conclusion: One-year risk of stroke in TIAMS participants was lower than reported in previous studies. Early implementation of antiplatelet/anticoagulant therapies may have contributed to the low stroke recurrence.


2020 ◽  
Vol 11 ◽  
Author(s):  
Korinne Nicolas ◽  
Christopher Levi ◽  
Tiffany-Jane Evans ◽  
Patricia T. Michie ◽  
Parker Magin ◽  
...  

2016 ◽  
Vol 12 (1) ◽  
pp. 96-104 ◽  
Author(s):  
Layan Akijian ◽  
Danielle Ní Chróinín ◽  
Elizabeth Callaly ◽  
Niamh Hannon ◽  
Michael Marnane ◽  
...  

Background Few studies have directly compared stroke recurrence rates after stroke and transient ischemic attack, and the risk factors underlying early recurrence are poorly understood. We aimed to investigate risk factors for recurrent stroke after first stroke and transient ischemic attack in a population-based study. Methods The North Dublin Population Stroke Study applied multiple overlapping hot and cold pursuit methods, to ascertain hospital- and community-treated stroke and transient ischemic attack patients over a 12-month period. Inclusion criteria were: (1) Stroke-physician confirmed transient ischemic attack/ischemic stroke; (2) first-stroke/transient ischemic attack event within the ascertainment period. Patients were prospectively followed at 72 h, 7, 28 and 90 days. Results A total of 584 patients met eligibility criteria (172 transient ischemic attack, 412 stroke). More transient ischemic attack than stroke patients presented to medical attention with recurrent stroke (8.24% vs. 0.24%, p = 0.0002). Recurrent stroke was more common after transient ischemic attack than index stroke at each time-interval (at 72 h, 4.07% vs. 1.23%, p = 0.03; at 90 days, 13.45% vs. 5.72%, p = 0.002). Stroke recurrence at 90 days was also associated with delay seeking medical attention after the index event (OR 3.2, p = 0.001), delayed anti-platelet (OR 2.8, p = 0.001) and statin (OR 2.4, p = 0.009) treatment, carotid stenosis/occlusion (OR 2.4, p = 0.008). On multivariable analysis, transient ischemic attack as index event (adjusted OR 2.3, p = 0.02), delayed statin treatment (OR 2.5, p = 0.02), and carotid stenosis/occlusion (OR 2.4, p = 0.02) were independent predictors of 90-day recurrent stroke. Conclusion A combination of pathophysiological and behavioral factors was associated with early stroke recurrence risk. Improved public awareness to reduce delays to self-referral for transient ischemic attack symptoms is needed.


2020 ◽  
Vol 62 (10) ◽  
pp. 1279-1284
Author(s):  
Nikhil Hiremath ◽  
Mahesh Kate ◽  
Aneesh Mohimen ◽  
Chandrasekharan Kesavadas ◽  
P. N. Sylaja

2017 ◽  
Vol 12 (3) ◽  
pp. 321-325 ◽  
Author(s):  
Yilong Wang ◽  
Yi Lin ◽  
Xia Meng ◽  
Weiqi Chen ◽  
Guohua Chen ◽  
...  

Rationale and aim Little is known about the safety and efficacy of the combination of ticagrelor and aspirin in acute ischemic stroke. This study aimed to evaluate whether the combination of ticagrelor and aspirin was superior to that of clopidogrel and aspirin in reducing the 90-day high on-treatment platelet reactivity for acute minor stroke or transient ischemic attack, especially for carriers of cytochrome P450 2C19 loss-of-function allele. Sample size and design This study was designed as a prospective, multicenter, randomized, open-label, active-controlled, and blind-endpoint, phase II b trial. The required sample size was 952 patients. It was registered with ClinicalTrials.gov (NCT02506140). Study outcomes The primary outcome was the proportion of patients with high on-treatment platelet reactivity at 90 days. High on-treatment platelet reactivity is defined as the P2Y12 reaction unit >208 measured using the VerifyNow P2Y12 assay. Conclusion The Platelet Reactivity in Acute Non-disabling Cerebrovascular Events study explored whether ticagrelor combined with aspirin could reduce further the proportion of patients with high on-treatment platelet reactivity at 90 days after acute minor stroke or transient ischemic attack compared with clopidogrel and aspirin.


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