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

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.

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Comparative Effectiveness of Dual Antiplatelet Therapy With Aspirin and Clopidogrel Versus Aspirin Monotherapy in Mild-to-Moderate Acute Ischemic Stroke According to the Risk of Recurrent Stroke

Circulation Cardiovascular Quality and Outcomes ◽

10.1161/circoutcomes.119.006474 ◽

2020 ◽

Vol 13 (11) ◽

Author(s):

Hak-Loh Lee ◽

Joon-Tae Kim ◽

Ji Sung Lee ◽

Man-Seok Park ◽

Kang-Ho Choi ◽

...

Keyword(s):

Ischemic Stroke ◽

High Risk ◽

Acute Ischemic Stroke ◽

Antiplatelet Therapy ◽

Primary Outcome ◽

Dual Antiplatelet Therapy ◽

Recurrent Stroke ◽

Group Versus ◽

Vascular Events ◽

Treatment Type

Background: This study compared the effectiveness of dual antiplatelet therapy (DAPT) with clopidogrel-aspirin with that of aspirin monotherapy (AM) in mild-to-moderate acute ischemic stroke considering the risk of recurrent stroke using the Stroke Prognosis Instrument II (SPI-II) score. Methods: This study is a retrospective analysis of data from a prospective, nationwide, multicenter stroke registry database between January 2011 and July 2018. We included patients with mild-to-moderate (National Institutes of Health Stroke Scale score ≤10), acute (within 24 hours of onset), noncardioembolic ischemic stroke. The primary outcome was a 3-month composite of stroke (either hemorrhagic or ischemic), myocardial infarction, and all-cause mortality. Propensity scores using the inverse probability of treatment weighting method were used to mitigate baseline imbalances between the DAPT and AM groups and within each subgroup considering SPI-II scores. Results: Among the 15 430 patients (age, 66±13 years; men, 62.0%), 45.1% (n=6960) received DAPT and 54.9% (n=8470) received AM. Primary outcome events were significantly more frequent in the AM group (16.7%) than in the DAPT group (15.5%; P =0.03). Weighted Cox proportional hazards models showed a reduced risk of 3-month primary vascular events in the DAPT group versus the AM group (hazard ratio, 0.84 [0.78–0.92]; P <0.001), with no interaction between acute treatment type and SPI-II risk subgroups ( P interaction =0.44). However, among the high-risk patients with SPI-II scores >7, a substantially larger absolute benefit was observed for 3-month composite vascular events in the DAPT group (weighted absolute risk differences, 5.4%), whereas smaller absolute benefits were observed among patients in the low- or medium-risk SPI-II subgroups (1.7% and 2.4%, respectively). Conclusions: Treatment with clopidogrel-aspirin was associated with a reduction in 3-month vascular events compared with AM in mild-to-moderate acute noncardioembolic ischemic stroke patients. Larger magnitudes of the effects of DAPT with clopidogrel-aspirin were observed in the high-risk subgroup by SPI-II risk scores.

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Baseline D-Dimer Levels as a Risk Assessment Biomarker for Recurrent Stroke in Patients with Combined Atrial Fibrillation and Atherosclerosis

Journal of Clinical Medicine ◽

10.3390/jcm8091457 ◽

2019 ◽

Vol 8 (9) ◽

pp. 1457 ◽

Cited By ~ 2

Author(s):

Kang-Ho Choi ◽

Woo-Keun Seo ◽

Man-Seok Park ◽

Joon-Tae Kim ◽

Jong-Won Chung ◽

...

Keyword(s):

Atrial Fibrillation ◽

Risk Assessment ◽

Ischemic Stroke ◽

Confidence Interval ◽

Secondary Prevention ◽

Primary Outcome ◽

Outcome Measure ◽

Recurrent Stroke ◽

Primary Outcome Measure ◽

D Dimer

Background: We investigated the effect of D-dimer levels and efficacy of different antithrombotic therapies according to the baseline D-dimer levels on recurrent stroke in patients with atrial fibrillation (AF)-related stroke and atherosclerosis. Methods: We enrolled 1441 patients with AF-related stroke and atherosclerosis in this nationwide multicenter study. The primary outcome measure was the occurrence of recurrent ischemic stroke over a 3-year period. Results: High D-dimer levels (≥2 μg/mL) were significantly associated with higher risk of recurrent ischemic stroke (adjusted hazard ratio (HR), 1.80; 95% confidence interval (CI), 1.13–2.84; p = 0.012). The risk of recurrent stroke was similar between the anticoagulant and the antiplatelet groups in all subjects (adjusted HR, 0.78; 95% CI, 0.46–1.32; p = 0.369). However, in patients with high D-dimer levels (≥2 μg/mL), risk of recurrent stroke was significantly lower in the anticoagulant group than in the antiplatelet group (adjusted HR, 0.40; 95% CI, 0.18–0.87; p = 0.022). Conclusion: Our findings suggested that baseline D-dimer levels could be used as a risk assessment biomarker of recurrent stroke in patients with AF-related stroke and atherosclerosis. High D-dimer levels would facilitate the identification of patients who are more likely to benefit from anticoagulants to ensure secondary prevention of stroke.

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Antiplatelet Therapy in Acute Mild-Moderate Ischemic Stroke (ATAMIS): a parallel, randomised, open-label, multicentre, prospective study

Stroke and Vascular Neurology ◽

10.1136/svn-2018-000148 ◽

2018 ◽

Vol 3 (4) ◽

pp. 263-267 ◽

Cited By ~ 1

Author(s):

Xiaowen Hou ◽

Xiaoqiu Li ◽

Xinhong Wang ◽

Huisheng Chen

Keyword(s):

Adverse Events ◽

Ischaemic Stroke ◽

Antiplatelet Therapy ◽

Rational Design ◽

Dual Antiplatelet Therapy ◽

Prospective Trial ◽

Minor Stroke ◽

Efficacy And Safety ◽

Open Label ◽

Nihss Score

BackgroundA recent study shows that dual antiplatelet therapy with clopidogrel plus aspirin is superior to aspirin monotherapy for minor stroke, which is defined as a National Institutes of Health Stroke Scale (NIHSS)score of ≤3. However, acute mild-moderate ischaemic stroke (4≤NIHSS≤10) still needs aggressive antiplatelet intervention to prevent deterioration and recurrence of stroke. The efficacy and safety of dual antiplatelet therapy versus aspirin monotherapy in the population are not clear. A multicentre clinical trial is designed to evaluate the efficacy and safety of clopidogrel plus aspirin therapy versus aspirin monotherapy within 48 hours of symptom onset of mild-moderate ischaemic stroke.Methods/DesignThe study is a randomised, open-label, multicentre, prospective trial with a target enrolment of 2700 patients from 60 centres in Northeast China. A treatment allocation identification number to each enrolled patient will be provided by a random number generator. The follow-up time for the clopidogrel plus aspirin and aspirin monotherapy groups is 90 days. The primary efficacy endpoint is a stroke progression event, which is defined as ≥4 point increase in the NIHSS score in 48 hours. The second efficacy endpoints include new ischaemic stroke within 90 days, change in the NIHSS score within 14 days, modified Rankin Scale score on day 90 and other vascular or death events within 90 days. The safety endpoints include mucocutaneous haemorrhage, organ haemorrhage and intracranial haemorrhage, adverse events and severe adverse events. χ2 test, t-test (or Mann-Whitney test), survival analysis and Cox proportional hazards models will be conducted. The findings of the study may provide an important evidence for clinical practice for these patients.DiscussionThe trial will be conducted under a rational design and will provide valuable evidence on the appropriate treatment for this population.Ethics and disseminationThe study was reviewed and approved by the Ethics Committee of the General Hospital of Shen-Yang Military Region (no K(2016) 6).Trial registration numberNCT02869009; Pre-results.

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High-sensitive C-reactive protein and dual antiplatelet in intracranial arterial stenosis

Neurology ◽

10.1212/wnl.0000000000004928 ◽

2018 ◽

Vol 90 (6) ◽

pp. e447-e454 ◽

Cited By ~ 5

Author(s):

Jiejie Li ◽

Anxin Wang ◽

Xingquan Zhao ◽

Liping Liu ◽

Xia Meng ◽

...

Keyword(s):

High Risk ◽

Antiplatelet Therapy ◽

Dual Antiplatelet Therapy ◽

Recurrent Stroke ◽

Arterial Stenosis ◽

Minor Stroke ◽

Intracranial Arterial Stenosis ◽

C Reactive Protein ◽

Vascular Events ◽

Reactive Protein

ObjectiveTo determine the relationship of high-sensitive C-reactive protein (hsCRP) and the efficacy and safety of dual antiplatelet therapy in patients with and without intracranial arterial stenosis (ICAS) in the Clopidogrel in High-Risk Patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial.MethodsA subgroup of 807 patients with both magnetic resonance angiography images and hsCRP measurement was analyzed. Cox proportional hazards models were used to assess the interaction of hsCRP levels with the effects of dual and single antiplatelet therapy.ResultsA total of 358 (44.4%) patients had ICAS and 449 (55.6%) did not. The proportion of patients with elevated hsCRP levels was higher in the ICAS group than in the non-ICAS group (40.2% vs 30.1%, p = 0.003). There was significant interaction between hsCRP and the 2 antiplatelet therapy groups in their effects on recurrent stroke after adjustment for confounding factors in the patients with ICAS (p = 0.012), but not in those without (p = 0.256). Compared with aspirin alone, clopidogrel plus aspirin significantly reduced the risk of recurrent stroke only in the patients with ICAS and nonelevated hsCRP levels (adjusted hazard ratio 0.27; 95% confidence interval 0.11 to 0.69; p = 0.006). Similar results were observed for composite vascular events. No significant difference in bleeding was found.ConclusionsPresence of both ICAS and nonelevated hsCRP levels may predict better response to dual antiplatelet therapy in reducing new stroke and composite vascular events in minor stroke or high-risk TIA patients. Further large-scale randomized and controlled clinical trials are needed to confirm this finding.

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Dual antiplatelet therapy with aspirin and clopidogrel for acute high risk transient ischaemic attack and minor ischaemic stroke: a clinical practice guideline

BMJ ◽

10.1136/bmj.k5130 ◽

2018 ◽

pp. k5130 ◽

Cited By ~ 21

Author(s):

Kameshwar Prasad ◽

Reed Siemieniuk ◽

Qiukui Hao ◽

Gordon Guyatt ◽

Martin O’Donnell ◽

...

Keyword(s):

High Risk ◽

Ischaemic Stroke ◽

Antiplatelet Therapy ◽

Transient Ischaemic Attack ◽

Dual Antiplatelet Therapy ◽

Recurrent Stroke ◽

Minor Stroke ◽

Strong Recommendation ◽

Ischaemic Attack

What is the role of dual antiplatelet therapy after high risk transient ischaemic attack or minor stroke? Specifically, does dual antiplatelet therapy with a combination of aspirin and clopidogrel lead to a greater reduction in recurrent stroke and death over the use of aspirin alone when given in the first 24 hours after a high risk transient ischaemic attack or minor ischaemic stroke? An expert panel produced a strong recommendation for initiating dual antiplatelet therapy within 24 hours of the onset of symptoms, and for continuing it for 10-21 days. Current practice is typically to use a single drug

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Dual Antiplatelet Therapy Using Cilostazol in Patients With Stroke and Intracranial Arterial Stenosis

Journal of the American Heart Association ◽

10.1161/jaha.121.022575 ◽

2021 ◽

Author(s):

Shinichiro Uchiyama ◽

Kazunori Toyoda ◽

Katsuhiro Omae ◽

Ryotaro Saita ◽

Kazumi Kimura ◽

...

Keyword(s):

Ischemic Stroke ◽

Antiplatelet Therapy ◽

Dual Antiplatelet Therapy ◽

Recurrent Stroke ◽

Controlled Trial ◽

Japanese Patients ◽

Arterial Stenosis ◽

Intracranial Arterial Stenosis ◽

Vascular Events ◽

Unique Identifier

Background Long‐term benefit of dual antiplatelet therapy (DAPT) over single antiplatelet therapy (SAPT) for the prevention of recurrent stroke has not been established in patients with intracranial arterial stenosis. We compared the efficacy and safety of DAPT with cilostazol and clopidogrel or aspirin to those of SAPT with clopidogrel or aspirin in patients with intracranial arterial stenosis, who were recruited to the Cilostazol Stroke Prevention Study for Antiplatelet Combination trial, a randomized controlled trial in high‐risk Japanese patients with ischemic stroke. Methods and Results We compared the vascular and hemorrhagic events between DAPT and SAPT in patients with ischemic stroke and symptomatic or asymptomatic intracranial arterial stenosis of at least 50% in a major intracranial artery. Patients were placed in two groups: 275 were assigned to receive DAPT and 272 patients SAPT. The risks of ischemic stroke (hazard ratio [HR], 0.47; 95% CI, 0.23–0.95); and composite of stroke, myocardial infarction, and vascular death (HR, 0.48; 95% CI, 0.26–0.91) were lower in DAPT than SAPT, whereas the risk of severe or life‐threatening bleeding (HR, 0.72; 95% CI, 0.12–4.30) did not differ between the 2 treatment groups. Conclusions DAPT using cilostazol was superior to SAPT with clopidogrel or aspirin for the prevention of recurrent stroke and vascular events without increasing bleeding risk among patients with intracranial arterial stenosis after stroke. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01995370.

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Efficacy of Clopidogrel for Prevention of Stroke Based on CYP2C19 Allele Status in the POINT Trial

Stroke ◽

10.1161/strokeaha.119.028713 ◽

2020 ◽

Vol 51 (7) ◽

pp. 2058-2065 ◽

Cited By ~ 1

Author(s):

James F. Meschia ◽

Ronald L. Walton ◽

Luca P. Farrugia ◽

Owen A. Ross ◽

Jordan J. Elm ◽

...

Keyword(s):

Ischemic Stroke ◽

Treatment Group ◽

Antiplatelet Therapy ◽

Significant Interaction ◽

Dual Antiplatelet Therapy ◽

Recurrent Stroke ◽

Therapy Group ◽

Group Versus ◽

Loss Of Function ◽

Allele Status

Background and Purpose: Clopidogrel is an antiplatelet drug that is metabolized to its active form by the CYP2C19 enzyme. The CHANCE trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events) found a significant interaction between loss-of-function allele status for the CYP2C19 gene and the effect of dual antiplatelet therapy with aspirin and clopidogrel on the rate of early recurrent stroke following acute transient ischemic attack/minor stroke. The POINT (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke Trial), similar in design to CHANCE but performed largely in North America and Europe, demonstrated a reduction in early recurrent stroke with dual antiplatelet therapy compared with aspirin alone. This substudy was done to evaluate a potential interaction between loss-of-function CYP2C19 alleles and outcome by treatment group in POINT. Methods: Of the 269 sites in 10 countries that enrolled patients in POINT, 134 sites participated in this substudy. DNA samples were genotyped for CYP2C19 *2, *3, and *17 alleles and classified as being carriers or noncarriers of loss-of-function alleles. Major ischemia consisted of ischemic stroke, myocardial infarction, or ischemic vascular death. Results: Nine hundred thirty-two patients provided analyzable DNA. The rates of major ischemia were 6.7% for the aspirin group versus 2.3% for the dual antiplatelet therapy group (hazard ratio, 0.33 [95% CI, 0.09–1.21]; P =0.09) among carriers of loss-of-function allele. The rates of major ischemia were 5.6% for the aspirin group versus 3.7% for the dual antiplatelet therapy group (hazard ratio, 0.65 [95% CI, 0.32–1.34]; P =0.25) among noncarriers. There was no significant interaction by genotype for major ischemia ( P =0.36) or stroke ( P =0.33). Conclusions: This substudy of POINT found no significant interaction with CYP2C19 loss-of-function carrier status and outcome by treatment group. Failure to confirm the findings from the CHANCE trial may be because the loss-of-function alleles tested are not clinically important in this context or because the 2 trials had differences in racial/ethnic composition. Additionally, differences between the 2 trials might be due to chance as our statistical power was limited to 50%. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00991029.

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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

Drug Metabolism and Personalized Therapy ◽

10.1515/dmdi-2021-0104 ◽

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.

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

Stroke ◽

10.1161/str.48.suppl_1.1 ◽

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.

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