scholarly journals 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

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.

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.

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

Neurology ◽  
2018 ◽  
Vol 90 (6) ◽  
pp. e447-e454 ◽  
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.

scholarly journals CHA2DS2-VASc score in acute ischemic stroke with atrial fibrillation: results from the Clinical Research Collaboration for Stroke in Korea

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hak-Loh Lee ◽  
Joon-Tae Kim ◽  
Ji Sung Lee ◽  
Beom Joon Kim ◽  
Jong-Moo Park ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Primary Outcome ◽  
Research Collaboration ◽  
Recurrent Stroke ◽  
Oral Anticoagulants ◽  
Vascular Events ◽  
Stroke Registry ◽  
One Year

AbstractWe investigated a multicenter registry to identify estimated event rates according to CHA2DS2-VASc scores in patients with acute ischemic stroke (AIS) and atrial fibrillation (AF). The additional effectiveness of antiplatelets (APs) plus oral anticoagulants (OACs) compared with OACs alone considering the CHA2DS2-VASc scores was also explored. This study retrospectively analyzed a multicenter stroke registry between Jan 2011 and Nov 2017, identifying patients with acute ischemic stroke with AF. The primary outcome event was a composite of recurrent stroke, myocardial infarction, and all-cause mortality within 1 year. A total of 7395 patients (age, 73 ± 10 years; men, 54.2%) were analyzed. The primary outcome events at one year ranged from 5.99% (95% CI 3.21–8.77) for a CHA2DS2-VASc score of 0 points to 30.45% (95% CI 24.93–35.97) for 7 or more points. After adjustments for covariates, 1-point increases in the CHA2DS2-VASc score consistently increased the risk of primary outcome events (aHR 1.10 [1.06–1.15]) at 1-year. Among OAC-treated patients at discharge (n = 5500), those treated with OAC + AP (vs. OAC alone) were more likely to experience vascular events, though among patients with a CHA2DS2-VASc score of 5 or higher, the risk of primary outcome in the OAC + AP group was comparable to that in the OAC alone group (Pint = 0.01). Our study found that there were significant associations of increasing CHA2DS2-VASc scores with the increasing risk of vascular events at 1-year in AIS with AF. Further study would be warranted.

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

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.

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

Stroke ◽  
2020 ◽  
Vol 51 (7) ◽  
pp. 2058-2065 ◽  
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.

Abstract TP416: Comparative Effectiveness of Addition of Antiplatelet to Oral Anticoagulant in Acute Ischemic Stroke With Atrial Fibrillation

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Joon-tae Kim ◽  
Hee-Joon Bae ◽  
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Oral Anticoagulant ◽  
Recurrent Stroke ◽  
Cox Proportional Hazards ◽  
Large Artery ◽  
Vascular Events ◽  
Nihss Score ◽  
Composite Events

Introduction: Atrial fibrillation (AF) and large artery diseases (LAD) share several risk factors and often coexist in the same patient. Optimal treatments for acute ischemic stroke (AIS) patients with concomitant AF and LAD have not been extensively studied so far. Objective: This study aimed to compare the effectiveness of the addition of antiplatelet (AP) to oral anticoagulant (OAC) with that of OAC alone in AIS with AF according to the LAD. Methods: Using a multicenter stroke registry, acute (within 48h of onset) and mild-to-moderate (NIHSS score ≤15) stroke patients with AF were identified. Propensity scores using IPTW were used to adjust baseline imbalances between the OAC+AP group and the OAC alone group in all patients and in each subgroup by LAD. The primary outcome was major vascular events, defined as the composite of recurrent stroke, MI, and all-cause mortality at up to 3 months after index stroke. Results: Among the 5469 patients (age, 72±10yrs; male, 54.9%; initial NIHSS score, 4 [2-9]), 79.0% (n=4323) received OAC alone, and 21.0% (n=1146) received OAC+AP. By weighted Cox proportional hazards analysis, a tendency of increasing the risk of 3-months primary composite events in the OAC+AP group vs the OAC alone (HR 1.36 [0.99-1.87], p=0.06), with significant interaction with treatments and LAD (Pint=0.048). Briefly, among patients with moderate-to-severe large artery stenosis, tendency of decrease in 3-months primary composite events of the OAC+AP group, compared with OAC alone group, was observed (HR 0.54 [0.17-1.70]), whereas among patients with complete occlusion, the OAC+AP group markedly increased the risk of 3-months composite events (HR 2.00 [1.27-3.15]), compared with the OAC alone group. No interaction between direct oral anticoagulant and warfarin on outcome was observed (Pint=0.35). Conclusion: In conclusion, treatment with addition of AP to OAC had a tendency to increase the risk of 3-months vascular events, compared with OAC alone in AIS with AF. However, the effects of antithrombotic treatment could be modified according to the LAD, with substantial benefits of OAC alone in subgroup of large artery occlusion. Our results address the need for the further study to tailor the optimal treatment in AIS with concomitant AF and LAD.

Abstract 19892: Association Between Estimated-glomerular Filtration Rate and Clinical Outcomes at One Year After Acute Ischemic Stroke

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
xiaoqing bu ◽  
Yonghong Zhang ◽  
Tan Xu ◽  
Hao Peng ◽  
Jing Chen ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Confidence Interval ◽  
Acute Ischemic Stroke ◽  
Filtration Rate ◽  
Estimated Glomerular Filtration Rate ◽  
Recurrent Stroke ◽  
Vascular Events ◽  
Hazard Ratios ◽  
All Cause Mortality ◽  
The Relationship

Introduction: The relationship between estimated-glomerular filtration rate (eGFR) and acute ischemic stroke outcomes remains controversial. Hypothesis: We aimed to evaluate the impact of eGFR on all-cause mortality, recurrent stroke, and vascular events in patients with acute ischemic stroke. Methods: 4036 patients with acute ischemic stroke recruited from 26 hospitals across China from August 2009 to May 2013 were included in our study. GFR was estimated by CKD-EPI equations based on serum creatinine and/or cystatin C (CKD-EPIcr, CKD-EPIcys, and CKD-EPIcr-cys). The Cox proportional hazards models were used to examine the relationship between declined eGFR and 1-year all-cause mortality, recurrent stroke, and vascular events. Declined eGFR was defined as <60 mL/min /1.73 m2. Results: Declined eGFR was present in 7.22% (n=281) of patients based on the CKD-EPIcr equation, 3.43% (n=119) based on the CKD-EPIcys equation, and 5.67% (n=170) based on the CKD-EPIcr-cys equation. Compared to patients with an eGFR ≥90 mL/min /1.73 m2, adjusted hazard ratios (95% confidence interval) for all-cause mortality associated with eGFR<60 mL/min /1.73 m2 were 1.68 (1.06 to 2.66, p=0.026), 2.29 (1.29 to 4.06, p=0.005), and 1.79 (1.08 to 2.98, p=0.024) using CKD-EPIcr, CKD-EPIcys, and CKD-EPIcr-cys equations, respectively. For recurrent stroke, adjusted hazard ratios (95% confidence interval) were 0.90 (0.49 to 1.66, p=0.743), 0.60 (0.19 to 1.93, p=0.393), and 0.89 (0.40 to 1.95, p=0.762), respectively. For vascular events, adjusted hazard ratios (95% confidence interval) were 1.33 (0.81 to 2.19, p=0.266), 1.07 (0.46 to 2.47, p=0.880), and 1.31 (0.70 to 2.43, p=0.403), respectively. Conclusion: Our study indicates that declined eGFR is a strong independent risk factor for total mortality among patients with acute ischemic stroke. However, there is no association between low eGFR and recurrent stroke or vascular events among patients with acute ischemic stroke. In addition, the association of eGFR with all-cause mortality among patients with acute ischemic stroke is stronger when eGFR was calculated based on the CKD-EPIcys equation compared to CKD-EPIcr and CKD-EPIcr-cys equations.

Lp-PLA2 and dual antiplatelet agents in intracranial arterial stenosis

Neurology ◽  
2019 ◽  
Vol 94 (2) ◽  
pp. e181-e189 ◽  
Author(s):  
Ming Yang ◽  
Anxin Wang ◽  
Jiejie Li ◽  
Xingquan Zhao ◽  
Liping Liu ◽  
...  
Keyword(s):  
High Risk ◽  
Antiplatelet Therapy ◽  
Proportional Hazards ◽  
Dual Antiplatelet Therapy ◽  
Cox Proportional Hazards ◽  
Arterial Stenosis ◽  
Minor Stroke ◽  
Activity Levels ◽  
Intracranial Arterial Stenosis ◽  
Vascular Events

ObjectiveTo evaluate the interaction effect of lipoprotein-associated phospholipase A2 (Lp-PLA2) activity on the efficacy and safety of dual/single antiplatelet therapy in patients with and without intracranial arterial stenosis (ICAS) by the Clopidogrel in High-Risk Patients with Acute Non-disabling Cerebrovascular Events trial.MethodsPatients with both MRI analysis and Lp-PLA2 testing results were included in the current subanalysis. The interaction of Lp-PLA2 activity with the effects of dual and single antiplatelet therapy were analyzed through Cox proportional hazards regressions model.ResultsAmong the 797 patients, the mean age was 63.1 ± 10.8 years, 518 (65%) were men, 356 (44.7%) had ICAS, and 441 (55.3%) did not. There were significantly more patients with elevated Lp-PLA2 activity in the ICAS group than in the non-ICAS group (43.8% vs 35.4%, p = 0.02). There was significant interaction between Lp-PLA2 activity levels and the 2 antiplatelet therapies for prevention of stroke recurrences and combined vascular events even after adjustment for confounding factors exclusively for patients with ICAS (p = 0.017, 0.017, respectively), but not for those without (p = 0.332, 0.674, respectively). Compared with aspirin alone, dual antiplatelet therapy significantly reduced the risk of stroke recurrences and combined vascular events (adjusted hazard ratio 0.33 [0.12–0.89], p = 0.028; 0.33 [0.12–0.89], p = 0.028, respectively) for patients with ICAS and nonelevated Lp-PLA2 activity.ConclusionsPresence of both ICAS and nonelevated Lp-PLA2 activity may predict better response to dual antiplatelet therapy in prevention of recurrent strokes and combined vascular events for patients with minor stroke or high-risk TIA.Clinicaltrials.gov identifierNCT00979589.

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