Prevalence of CYP2C19*2 carriers in Saudi ischemic stroke patients and the suitability of using genotyping to guide antiplatelet therapy in a university hospital setup

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Abdullah M. Al-Rubaish ◽  
Fahad A. Al-Muhanna ◽  
Abdullah M. Alshehri ◽  
Abdulla A. Alsulaiman ◽  
Majed M. Alabdulali ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Antiplatelet Therapy ◽  
Dual Antiplatelet Therapy ◽  
Recurrent Stroke ◽  
University Hospital ◽  
Normal Allele ◽  
Stroke Patients ◽  
Stroke Event ◽  
Increased Risk ◽  
Age And Sex

Abstract Objectives To mitigate the incidence of recurrent stroke in patients, dual antiplatelet therapy comprising aspirin and clopidogrel is usually administered. Clopidogrel is a prodrug and its bioactivation is catalyzed by cytochrome P450 (CYP)2C19. The main objective of this work was to determine the prevalence of CYP2C19*2 carriers in Saudi ischemic stroke patients and assess the suitability of using genotyping to guide antiplatelet therapy in a university hospital setup. Methods This prospective (2018–2019) study was conducted on 256 patients (age 61 ± 12.5) clinically diagnosed with ischemic stroke who were genotyped using Spartan RX CYP2C19 assay. Results From the total patient group (256), upon admission, 210 patients were prescribed either aspirin, clopidogrel or dual antiplatelet therapy. Of the 27 patients with the CYP2C19*2 allele who were prescribed clopidogrel (18) or dual antiplatelet therapy (9), only 21 patients could be followed up for a period of six months post stroke event, in addition to 21 age- and sex-matched patients with the normal allele. The CYP2C19*2 allele carriers had a statistically significant increased risk of recurrent stroke compared to patients carrying the normal allele. Conclusions This study shows the suitability of using genotyping to guide antiplatelet therapy in ischemic stroke patients in a clinical setting.

Abstract 1: Dual Antiplatelet Therapy is More Effective for Multiple Acute Infarcts: Subgroup Analysis of Chance

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Yilong Wang ◽  
Jing Jing ◽  
Yongjun Wang
Keyword(s):  
Antiplatelet Therapy ◽  
Dual Antiplatelet Therapy ◽  
Recurrent Stroke ◽  
Bleeding Event ◽  
Minor Stroke ◽  
Stroke Recurrence ◽  
Severe Bleeding ◽  
Stroke Patients ◽  
Acute Infarction ◽  
Increased Risk

Background and Purpose: TIAregistry.org project showed that TIA and minor stroke patients with multiple acute infarctions (MAIs), which represent mechanisms of embolism, are at higher risk of recurrent stroke as compared to those with none or single acute infarction (SAI). We hypothesis that patient with MAIs may be more susceptible to dual antiplatelet therapy. Methods: We compared clopidogrel plus aspirin with aspirin alone with regard to their effectiveness and safety for prevention of stroke recurrence among non-cardiac TIA and minor ischemic stroke patients with different infarction patterns (no acute infarction, SAI, or MAIs) in the imaging subgroup from the Clopidogrel in High-Risk Patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial. The efficacy and safety outcome were stroke recurrence and moderate-to-severe bleeding event at 90 days respectively. Results: Overall, 1089 patients at 45 centers in CHANCE trial were included. The rate of recurrent stroke was 14.2%, 8.7%, and 2.0% in patients with MAIs, SAI and no infarction respectively at 90 days. Increased risk of stroke recurrence was observed in patients with MAIs (HR, 5.9; 95% CI, 2.3-15.2) and SAI (HR, 4.1; 95% CI, 1.6-10.7) (Figure A) as compared to those without infarction. The dual antiplatelet treatment was superior to aspirin alone for reducing the risk of recurrent stroke in patients with MAIs (HR 0.48; 95% CI, 0.25- 0.92; P = 0.03) but not in patients with SAI and without acute infarction with P=0.046 for interaction (Figure B-D). The effect of treatment assignment on bleeding did not vary among groups with different infarction patterns ( P >0.05 for all). Conclusions: Patients with MAIs had the highest risk for stroke recurrence among patients with different infarction patterns. Patients with MAIs may benefit the most clinically from dual antiplatelet therapy and dual antiplatelet therapy does not increase the risk of hemorrhage among any groups.

Abstract P132: Clinical Outcomes In Ischemic Stroke Patients With Uncontrolled Hypertension

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Zahra Abuzaid ◽  
Sara Almuslem ◽  
Farah Aleisa
Keyword(s):  
Blood Pressure ◽  
Ischemic Stroke ◽  
Clinical Outcomes ◽  
Recurrent Stroke ◽  
Uncontrolled Hypertension ◽  
Stroke Recurrence ◽  
Stroke Patients ◽  
Stroke Event ◽  
Uncontrolled Blood Pressure

Background: Hypertension is considered major risk factor for incidence of ischemic stroke, controlling blood pressure reduces this risk, the relationship of uncontrolled blood pressure and stroke outcomes is complex, post stroke uncontrolled blood pressure remains one of the major contributing factors for stroke recurrence and mortality, in our study we studied the long term effects of uncontrolled hypertension in modern health care setting. Methodology: Patients in the study were admitted to the neurology department at KFSH-D between March 2015- August 2019, we included 102 acute ischemic stroke patients whom had hypertension, all patients had follow up appointments at stroke clinic a minimum of 2 visits over 4 years. We retrospectively compared blood pressure data from stroke patients with recurrent ischemic stroke events vs. patients with initial stroke event, and recurrent stroke, also we studied blood pressure readings for different stroke severity groups, patients who had severe stroke with mRS>4, compared to milder stroke group of mRS<4. Results: We found 48 patients identified with recurrent stroke event, those with uncontrolled hypertension had significantly higher stroke recurrence events (P=0.002), despite acute stroke treatment, patients who had history of uncontrolled hypertension were found to have more severe stroke deficits than those who had controlled blood pressure (P=0.029). We found significant difference in the long term stroke clinical outcomes between patients who had uncontrolled blood pressure and patients who had controlled blood pressure recordings within the same hospital setting (P=0.064). Conclusion: Based on our findings, uncontrolled hypertension was associated with higher risk of stroke recurrence, it also increased susceptibility to worse stroke clinical outcomes up to 1 year after initial stroke event, which deserved further close attention and better blood pressure control.

Abstract 104: Disability After Minor Stroke and TIA in the POINT Trial

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Brett L Cucchiara ◽  
Jordan Elm ◽  
J Donald Easton ◽  
Shelagh Coutts ◽  
Joshua Willey ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Adverse Events ◽  
Antiplatelet Therapy ◽  
Primary Outcome ◽  
Dual Antiplatelet Therapy ◽  
Recurrent Stroke ◽  
Primary Outcome Measure ◽  
Minor Stroke ◽  
Serious Adverse Events ◽  
Index Event

Background and Purpose: To assess the effect of combination antiplatelet therapy with aspirin and clopidogrel versus aspirin alone on disability following TIA or minor stroke and to identify factors associated with disability. Methods: The POINT trial randomized patients with TIA or minor stroke (NIHSS≤3) within 12 hours of onset to dual antiplatelet therapy (DAPT) with aspirin plus clopidogrel versus aspirin alone. The primary outcome measure was a composite of stroke, MI, or vascular death. We performed a post-hoc exploratory analysis to examine the effect of treatment on overall disability (defined as mRS>1) at 90 days as well as disability ascribed by the local investigator to index or recurrent stroke. We also evaluated predictors of disability. Results: At 90 days, 188/1964 (9.6%) of patients enrolled with TIA and 471/2586 (18.2%) of those enrolled with stroke were disabled. Overall disability was similar between patients assigned DAPT versus aspirin alone (14.7% vs. 14.3%, OR 0.97, 95%CI 0.82-1.14, p=0.69). However, there were numerically fewer patients with disability in conjunction with a primary outcome event in the DAPT arm (3.0% vs. 4.0%, OR 0.73, 95%CI 0.53-1.01, p=0.06), and significantly fewer patients in the DAPT arm with disability attributed by the investigators to either the index event or recurrent stroke (5.9% vs. 7.4%, OR 0.78, 95% CI 0.62-0.99, p=0.04). Notably, disability attributed to the index event accounted for the majority of this difference (4.5% vs. 6.0%, OR 0.74 95% CI 0.57-0.96, p=0.02). In multivariate analysis of patients enrolled with TIA, disability was significantly associated with age, subsequent ischemic stroke, serious adverse events, and major bleeding. In patients enrolled with stroke, disability was associated with female sex, hypertension, diabetes, NIHSS score, recurrent ischemic stroke, subsequent myocardial infarction, and serious adverse events. Conclusions: In addition to reducing recurrent stroke in patients with acute minor stroke and TIA, dual antiplatelet therapy might reduce stroke-related disability.

scholarly journals A Study of Comorbidities Among Stroke Patients Admitted In A Tertiary Level Hospital

KYAMC Journal ◽  
2019 ◽  
Vol 10 (3) ◽  
pp. 152-155
Author(s):  
Mohammad Iqbal Hossain ◽  
Ahmed Manadir Hossain ◽  
Quazi Shihab Uddin Ibrahimi
Keyword(s):  
Ischemic Stroke ◽  
Recurrent Stroke ◽  
Cross Sectional Study ◽  
Comorbid Condition ◽  
Stroke Patients ◽  
Stroke Event ◽  
College Hospital ◽  
Cross Sectional ◽  
Medical College ◽  
Number Of Patients

Introduction: Stroke is an important cause of disability among adults and is one of the leading causes of death worldwide. The reported prevalence of stroke in Bangladesh is 0.3%. Stroke patients have comorbidity Comorbidity is an important factor in stroke outcomes and burden. Objectives: This study was carried out with a view to find out the common comorbidities prevalent in stroke patients. Materials and Method: This cross sectional study was carried out in Faridpur Medical College Hospital from November 2018 to April 2019 to see the comorbidities and associated factors among admitted stroke patients. A total of 390 stroke patients were included. Data were collected by detailed history from patients or their relatives followed by thorough physical examination; Results: Among total respondents, majority was male (56.4%) and ischemic stroke was the commonest type of stroke (65.6%) diagnosed. The substantial number of patients (85.6%) had one or more comorbidities. Hypertension was the predominant comorbid condition (74.1%) followed by coronary heart disease ((19.5%), diabetes mellitus (17.4%), obesity (6.2%), hyperlipidemia (6.2%), CKD (4.9%), COPD (3.3%), malignancy (0.8%), hypothyroidism (0.5%),CLD (0.5%) and parkinsonism (0.3%). Comorbidities were present in 88.28% of ischemic stroke, 81.81% of intracerebral haemorrhage and 69.23% of subarachnoid hemorrhage cases. Patients with first stroke event have comorbidities in 83.64% cases where as in 95.45% cases of recurrent stroke patients. The relationship between comorbidity and mortality risk is not clear with approximately 16% death in both with or without comorbidity. Conclusion: The results of the study concluded that the prevalence of comorbidities in stroke patients remains high in our settings and the patients with increasing age and those with recurrent stroke events have statistically significant number of comorbid conditions. KYAMC Journal Vol. 10, No.-3, October 2019, Page 152-155

Dual antiplatelet therapy after carotid artery stenting: trends and outcomes in a large national database

2020 ◽  
Vol 13 (1) ◽  
pp. 8-13
Author(s):  
Eric S Sussman ◽  
Michael Jin ◽  
Arjun V Pendharkar ◽  
Benjamin Pulli ◽  
Austin Feng ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Carotid Artery ◽  
Antiplatelet Therapy ◽  
Carotid Artery Stenting ◽  
Dual Antiplatelet Therapy ◽  
National Database ◽  
Increased Risk ◽  
Hemorrhagic Complications ◽  
The Impact ◽  
Large National Database

BackgroundWhile dual antiplatelet therapy (dAPT) is standard of care following carotid artery stenting (CAS), the optimal dAPT regimen and duration has not been established.MethodsWe canvassed a large national database (IBM MarketScan) to identify patients receiving carotid endarterectomy (CEA) or CAS for treatment of ischemic stroke or carotid artery stenosis from 2007 to 2016. We performed univariable and multivariable regression methods to evaluate the impact of covariates on post-CAS stroke-free survival, including post-discharge antiplatelet therapy.ResultsA total of 79 084 patients diagnosed with ischemic stroke or carotid stenosis received CEA (71 178; 90.0%) or CAS (7906; 10.0%). After adjusting for covariates, <180 days prescribed post-CAS P2Y12-inhibition was associated with increased risk for stroke (<90 prescribed days HR=1.421, 95% CI 1.038 to 1.946; 90–179 prescribed days HR=1.484, 95% CI 1.045 to 2.106). The incidence of hemorrhagic complications was higher during the period of prescribed P2Y12-inhibition (1.16% per person-month vs 0.49% per person-month after discontinuation, P<0.001). The rate of extracranial hemorrhage was nearly six-fold higher while on dAPT (6.50% per patient-month vs 1.16% per patient-month, P<0.001), and there was a trend towards higher rate of intracranial hemorrhage that did not reach statistical significance (5.09% per patient-month vs 3.69% per patient-month, P=0.0556). Later hemorrhagic events beyond 30 days post-CAS were significantly more likely to be extracranial (P=0.028).ConclusionsIncreased duration of post-CAS dAPT is associated with lower rates of readmissions for stroke, and with increased risk of hemorrhagic complications, particularly extracranial hemorrhage. The potential benefit of prolonging dAPT with regard to ischemic complications must be balanced with the corresponding increased risk of predominantly extracranial hemorrhagic complications.

Abstract WP424: Efficacy Of Antiplatelet Therapy For Secondary Stroke Prevention Following Lacunar Stroke: A Meta-analysis And Pooled Analysis Of Randomized Controlled Trials

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Ashkan Shoamanesh ◽  
Chun Shing Kwok ◽  
Phyo K Myint ◽  
Yoon K Loke ◽  
Hannah Copley ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Antiplatelet Therapy ◽  
Stroke Prevention ◽  
Recurrent Stroke ◽  
Meta Analysis ◽  
Antiplatelet Agents ◽  
Pooled Analysis ◽  
Cochrane Library ◽  
Lacunar Stroke ◽  
Stroke Patients

INTRODUCTION: The predominant underlying mechanism of lacunar stroke differs from that of other ischemic stroke subtypes. Accordingly, so may the ideal stroke prevention regimen. We aimed to evaluate the efficacy of different antiplatelet agents in lacunar stroke patients. Method: We searched MEDLINE, EMBASE and the Cochrane library for RCTs that evaluated antiplatelet therapy in patients with ischemic stroke. Trials which provided stroke recurrence rates in patients presenting with lacunar stroke, or where the data was obtainable from manuscript authors were included. In addition, we included the novel SPS3 trial’s antiplatelet arm data presented at the 2011 ISC. We performed pooled analysis to assess the crude frequency of recurrent stroke and a random effects meta-analysis. Results: Lacunar stroke data was available for 12 trials encompassing 35, 218 participants (mean age 65, 65% male). The pooled crude recurrent stroke rate was least for cilostazol monotherapy (6.2%), followed by ASA monotherapy (7.4%), clopidogrel monotherapy (8.6%), ASA/dipyridamole (8.6%) and greatest for ASA/clopidogrel therapy (9.1%). Rate ratios of lacunar stroke patients suggest no significant efficacy advantage for ASA [ASA vs placebo (RR 0.72, 95% CI 0.34-1.50; p=0.38)], ASA/clopidogrel [ASA/clopidogrel vs ASA (RR 0.80, 95% CI 0.62-1.03; p=0.08), ASA/clopidogrel vs clopidogrel (RR 0.95, 95% CI 0.79-1.15; p=0.63)], sarpogrelate [sarpogrelate vs ASA (RR 1.31, 95% CI 0.84-2.04; p=0.23)] and ASA/dipyridamole [ASA/dipyridamole vs ASA (RR 0.90, 95% CI 0.70-1.16; p=0.042)] for recurrent stroke. The results from Japanese trials evaluating the efficacy of cilostazol found that it is significantly better than both placebo (RR 0.51, 95% CI 0.30-0.85; p=0.01) and ASA (RR 0.70, 95% CI 0.51-0.96; p=0.03) in the secondary prevention of stroke. Conclusions: There seems to be no significant advantage among the various antiplatelet agents studied in lacunar stroke patients apart for cilostazol. However, this requires confirmation within large randomized trials outside of Japanese populations.

scholarly journals WMH and long-term outcomes in ischemic stroke

Neurology ◽  
2019 ◽  
Vol 92 (12) ◽  
pp. e1298-e1308 ◽  
Author(s):  
Marios K. Georgakis ◽  
Marco Duering ◽  
Joanna M. Wardlaw ◽  
Martin Dichgans
Keyword(s):  
Ischemic Stroke ◽  
Functional Impairment ◽  
Recurrent Stroke ◽  
Meta Analysis ◽  
Sensitivity Analyses ◽  
Stroke Recurrence ◽  
Stroke Severity ◽  
Stroke Patients ◽  
Increased Risk

ObjectiveTo investigate the relationship between baseline white matter hyperintensities (WMH) in patients with ischemic stroke and long-term risk of dementia, functional impairment, recurrent stroke, and mortality.MethodsFollowing the Meta-analysis of Observational Studies in Epidemiology and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO protocol: CRD42018092857), we systematically searched Medline and Scopus for cohort studies of ischemic stroke patients examining whether MRI- or CT-assessed WMH at baseline are associated with dementia, functional impairment, recurrent stroke, and mortality at 3 months or later poststroke. We extracted data and evaluated study quality with the Newcastle–Ottawa scale. We pooled relative risks (RR) for the presence and severity of WMH using random-effects models.ResultsWe included 104 studies with 71,298 ischemic stroke patients. Moderate/severe WMH at baseline were associated with increased risk of dementia (RR 2.17, 95% confidence interval [CI] 1.72–2.73), cognitive impairment (RR 2.29, 95% CI 1.48–3.54), functional impairment (RR 2.21, 95% CI 1.83–2.67), any recurrent stroke (RR 1.65, 95% CI 1.36–2.01), recurrent ischemic stroke (RR 1.90, 95% CI 1.26–2.88), all-cause mortality (RR 1.72, 95% CI 1.47–2.01), and cardiovascular mortality (RR 2.02, 95% CI 1.44–2.83). The associations followed dose-response patterns for WMH severity and were consistent for both MRI- and CT-defined WMH. The results remained stable in sensitivity analyses adjusting for age, stroke severity, and cardiovascular risk factors, in analyses of studies scoring high in quality, and in analyses adjusted for publication bias.ConclusionsPresence and severity of WMH are associated with substantially increased risk of dementia, functional impairment, stroke recurrence, and mortality after ischemic stroke. WMH may aid clinical prognostication and the planning of future clinical trials.

scholarly journals Impact of Diabetes on Platelet Function in Acute Ischemic Stroke Patients Taking Dual Antiplatelet Therapy

2021 ◽  
Vol 12 ◽  
Author(s):  
Yinping Guo ◽  
Yi Zhang ◽  
Jing Zhao ◽  
Lingshan Wu ◽  
Zhiyuan Yu ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Antiplatelet Therapy ◽  
Platelet Function ◽  
Dual Antiplatelet Therapy ◽  
Platelet Reactivity ◽  
Significant Risk ◽  
Maximum Amplitude ◽  
Stroke Patients ◽  
Clot Strength

Objectives: Diabetes mellitus (DM) is a significant risk factor for ischemic stroke and associated with platelet reactivity. We aim to evaluate the effect of DM on platelet function in acute ischemic stroke patients taking dual antiplatelet therapy (DAPT).Methods: We consecutively included patients with acute ischemic stroke taking DAPT. Platelet function was assessed by thromboelastography and the arachidonic acid (AA) or adenosine diphosphate (ADP) induced platelet inhibition rate were used to confirmed the high-residual on-treatment platelet reactivity (HRPR) to aspirin or clopidogrel. We classified patients into DM and non-DM groups. The association between DM and platelet function was assessed and the confounding factors were adjusted by propensity score matching (PSM) analysis. The independent risk factors of HRPR were determined by multivariate logistic regression analysis.Results: A total of 1,071 acute ischemic stroke patients, 712 in the non-DM group and 359 in the DM group, were included. Patients with DM had a significantly higher maximum amplitude (63.0 vs. 62.0 mm, P &lt; 0.01), ADP-induced clot strength (34.6 vs. 30.3 mm, P &lt; 0.01) and clopidogrel HRPR rate (22.6% vs. 17.3%, P = 0.038) than those without DM. Among 662 patients after PSM, the maximum amplitude (63.1 vs. 62.5 mm, P = 0.032), ADP-induced clot strength (34.6 vs. 29.3 mm, P &lt; 0.01) and clopidogrel HRPR rate (23.0% vs. 15.7%, P = 0.018) is still higher in the DM group. DM was an independent factor of clopidogrel HRPR (OR = 1.48, 95% CI: 1.03–2.07, P &lt; 0.05).Conclusions: In acute ischemic stroke patients taking DAPT, DM is associated with increased platelet reactivity and higher prevalence of clopidogrel HRPR.

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