scholarly journals P.072 Ticagrelor vs Clopidogrel in Addition to Aspirin in Minor Ischemic Stroke/ TIA – a Systematic Review & Network Meta-Analysis (NMA)

Author(s):  
R Lun ◽  
S Dhaliwal ◽  
G Zitikyte ◽  
D Roy ◽  
B Hutton ◽  
...  

Background: Dual antiplatelet therapy (DAPT) is recommended after minor ischemic stroke/ transient ischemic attack (TIA), but Clopidogrel/ Aspirin has never been compared directly to Ticagrelor/ Aspirin. Our objective is to compare these regimens in terms of efficacy and safety. Methods: Medline, Embase, and Cochrane were searched for randomized controlled trials (RCTs) that enrolled adults with minor stroke/ TIA and administered antiplatelets within 72 hours. The primary efficacy outcome is recurrent stroke or death at 90 days. We performed a Bayesian-approach NMA. Between group comparisons were presented as odds-ratios (OR) with 95% credible intervals (95%CI). Sucraplots were based on calculated probabilities of rankings for individual outcomes. Results: 9/4014 studies were included: 5 RCTs and 4 subgroup analyses. 22,098 patients were analyzed. At 90 days, both DAPT regimens were superior to Aspirin in the prevention of recurrent stroke/ death. There was no significant difference between Clopidogrel/ ASA compared to Ticagrelor/ ASA (OR 0.90 [95%CI 0.74 – 1.09]), although Clopidogrel/ Aspirin was ranked #1 using Sucraplots. There was no significant difference between the interventions for mortality, bleeding, or adverse events. Conclusions: DAPT was superior to ASA in the prevention of recurrent strokes/ death, but there was no difference between Clopidogrel/ ASA and Ticagrelor/ ASA.

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0250553
Author(s):  
Gabriele Zitikyte ◽  
Danielle Carole Roy ◽  
Shan Dhaliwal ◽  
Ronda Lun ◽  
Brian Hutton ◽  
...  

Introduction Patients with minor ischemic stroke or transient ischemic attack represent a high-risk population for recurrent stroke. No direct comparison exists comparing dual antiplatelet therapy regimens—namely, Ticagrelor and Aspirin versus Clopidogrel and Aspirin. This systematic review and network meta-analysis (NMA) will examine the efficacy of these two different antiplatelet regimens in preventing recurrent stroke and mortality up to 30 days. Methods and analysis MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) will be searched with the assistance of a medical information specialist. Two independent reviewers will screen studies for inclusion; eligible studies will include randomized controlled trials that enrolled adults presenting with acute minor ischemic stroke or transient ischemic attack and compared one or more of the interventions against each other and/or a control. The primary outcomes will be recurrent ischemic stroke up to 30 days from symptom onset. Secondary outcomes will include safety outcomes (I.e. major bleeding and mortality), functional disability, and outcomes up to 90 days from symptom onset. A Bayesian approach to NMA will be implemented using the BUGSnet function in R Software. Between group comparisons for time-to-event (TTE) and dichotomous outcomes will be presented in terms of hazard ratios and odds ratios with 95% credible intervals, respectively. Secondary effect measures of treatment ranking will also be estimated. Ethics and dissemination No formal research ethics approval are necessary. We will disseminate our findings through scientific conference presentations, peer-reviewed publications, and social media/the press. The findings from this review will aid clinicians in decision-making on the choice of antithrombotic therapy in a high-risk stroke population and could be important in the development of future treatment trials and guidelines. Registration ID with Open Science Framework: 10.17605/OSF.IO/XDJYZ.


2021 ◽  
Vol 12 ◽  
Author(s):  
Xiao-Guang Zhang ◽  
Jing-Yu Gu ◽  
Qiang-Qiang Fu ◽  
Shi-Wu Chen ◽  
Jie Xue ◽  
...  

Background: Platelet endothelial aggregation receptor-1 (PEAR1) rs12041331 has been reported to affect agonist-stimulated platelet aggregation, but it remains unclear whether this variant plays a role in recurrent stroke. Here we assess the clinical relevance of PEAR1 rs12041331 in acute minor ischemic stroke (AMIS) and transient ischemic attack (TIA) Chinese patients treated with dual antiplatelet therapy (DAPT).Methods: We recruited 273 consecutive minor stroke and TIA patients, and Cox proportional hazard regression was used to model the relationship between PEAR1 rs12041331 and thrombotic and bleeding events.Results: Genotyping for PEAR1 rs12041331 showed 49 (18.0%) AA homozygotes, 129 (47.3%) GA heterozygotes, and 95 (34.7%) GG homozygotes. No association was observed between PEAR1 rs12041331 genotype and stroke or composite clinical vascular event rates (ischemic stroke, hemorrhagic stroke, TIA, myocardial infarction, or vascular death) or bleeding events regardless if individuals carried one or two copies of the A allele. Our results suggested that rs12041331 genetic polymorphism was not an important contributor to clinical events in AMIS and TIA patients in the setting of secondary prevention.Conclusions: Our data do provide robust evidence that genetic variation in PEAR1 rs12041331 do not contribute to atherothrombotic or bleeding risk in minor stroke and TIA patients treated with DAPT.


2021 ◽  
Vol 27 ◽  
Author(s):  
Francesco Condello ◽  
Gaetano Liccardo ◽  
Giuseppe Ferrante

Background: Evidence about the use of dual antiplatelet therapy (DAPT) with aspirin and P2Y12 inhibitors in patients with acute minor ischemic stroke or transient ischemic attack (TIA) is emerging. The aim of our study was to provide an updated and comprehensive analysis about the risks and benefits of DAPT versus aspirin monotherapy in this setting. Methods: The PubMed, Embase, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov databases, main international conference proceedings were searched for randomized controlled trials comparing DAPT versus aspirin monotherapy in patients with acute ischemic stroke or TIA not eligible for thrombolysis or thrombectomy presenting in the first 24 hours after the acute event. Data were pooled by meta-analysis using a random-effects model. The primary efficacy endpoint was ischemic stroke recurrence, and the primary safety outcome was major bleeding. Secondary endpoints were intracranial hemorrhage, hemorrhagic stroke, and all-cause death. Results: A total of 4 studies enrolling 21,459 patients were included. DAPT with clopidogrel was used in 3 studies, DAPT with ticagrelor in one study. DAPT duration was 21 days in one study, 1 month in one study, and 3 months in the remaining studies. DAPT was associated with a significant reduction in the risk of ischemic stroke recurrence (relative risk [RR], 0.74; 95% confidence interval [CI], 0.67-0.82, P<0.001, number needed to treat 50 [95% CI 40-72], while it was associated with a significantly higher risk of major bleeding (RR, 2.59; 95% CI 1.49-4.53, P=0.001, number needed to harm 330 [95% CI 149-1111]), of intracranial hemorrhage (RR 3.06, 95% CI 1.41-6.66, P=0.005), with a trend towards higher risk of hemorrhagic stroke (RR 1.83, 95% CI 0.83-4.05, P=0.14), and a slight tendency towards higher risk of all-cause death (RR 1.30, 95% CI 0.89-1.89, P=0.16). Conclusions: Among patients with acute minor ischemic stroke or TIA, DAPT, as compared with aspirin monotherapy, might offer better effectiveness in terms of ischemic stroke recurrence at the expense of a higher risk of major bleeding. The trade-off between ischemic benefits and bleeding risks should be assessed in tailoring the therapeutic strategies.


Stroke ◽  
2021 ◽  
Author(s):  
Hans-Christoph Diener ◽  
Aurauma Chutinet ◽  
J. Donald Easton ◽  
Christopher B. Granger ◽  
Eva Kleine ◽  
...  

Background and Purpose: Patent foramen ovale (PFO) may increase the risk of embolic stroke of undetermined source (ESUS). Guidelines suggest anticoagulation may be more effective than antiplatelets in preventing stroke in patients with ESUS and PFO when interventional closure is not performed. Methods: Patients with ESUS randomized to dabigatran (150/110 mg BID) or aspirin (100 mg QD) from the RE-SPECT ESUS study (Randomized, Double-Blind, Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate Versus Acetylsalicylic Acid in Patients With Embolic Stroke of Undetermined Source) were included. The rate of recurrent stroke (primary end point) and ischemic stroke was reported for patients with and without baseline PFO. A meta-analysis comparing the effects of anticoagulant and antiplatelet therapy on ischemic stroke in patients with PFO was updated to include RE-SPECT ESUS. Results: PFO was present in 680 of 5388 (12.6%) patients with documented PFO status. The risk of recurrent stroke with dabigatran versus aspirin was similar in patients with and without PFO ( P for interaction, 0.8290). In patients with PFO, the meta-analysis found no statistically significant difference between anticoagulant and antiplatelet therapy (odds ratio, 0.70 [95% CI, 0.43–1.14]) for ischemic stroke. Conclusions: There is insufficient evidence to recommend anticoagulation over antiplatelet therapy for patients with ESUS and a PFO. More data are needed to guide antithrombotic therapy in this population. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02239120.


Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Katrina Hannah Ignacio ◽  
Jose Danilo Diestro ◽  
Adrian Espiritu ◽  
Julian Spears ◽  
Maria Cristina San Jose

Background: Current guidelines for intravenous tissue plasminogen activator for acute ischemic stroke preclude the administration of the drug in patients with a history of recent stroke. Objectives: Our meta-analysis aims to determine the safety and efficacy of thrombolysis in patients with early recurrent ischemic stroke (within 3 months of initial stroke). Methods: Pubmed, Cochrane, Scopus, Embase, Clinicaltrials.gov , and HERDIN were searched for studies comparing the outcomes of acute stroke patients undergoing intravenous thrombolysis between those with early recurrent stroke (ERS) and those without. Random-effects meta-analysis was used to evaluate the outcomes in terms of symptomatic intracranial hemorrhage, mortality and good functional outcomes at 3 months (modified Rankin Score < 2 ) Results: Three observational studies with a total of 48,459 thrombolysed patients (824 with ERS and 47,635 without) were included in the study. There was no significant difference between patients with ERS and those without in terms of symptomatic intracranial hemorrhage (OR 1.39, 95% Confidence Interval [CI] 0.75-2.58), mortality (OR 1.36, 95% CI 0.60-3.09) and good functional outcomes at 3 months (OR 0.74, 95% CI 0.47-1.16). Conclusion: Our meta-analysis suggests that there is insufficient evidence to substantiate excluding patients with ERS from receiving thrombolysis. Further studies to re-examine ERS as an exclusion criterion for receiving thrombolysis are warranted.


Neurology ◽  
2017 ◽  
Vol 88 (11) ◽  
pp. 1081-1088 ◽  
Author(s):  
Yuesong Pan ◽  
Xia Meng ◽  
Jing Jing ◽  
Hao Li ◽  
Xingquan Zhao ◽  
...  

Objective:To estimate the association of different patterns of infarction and intracranial arterial stenosis (ICAS) with the prognosis of acute minor ischemic stroke and TIA.Methods:We derived data from the Clopidogrel in High-risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) trial. A total of 1,089 patients from 45 of 114 participating sites of the trial undergoing baseline MRI/angiography were included in this subgroup analysis. Patterns of infarction and ICAS were recorded for each individual. The primary efficacy outcome was an ischemic stroke at the 90-day follow-up. We assessed the associations between imaging patterns and prognosis of patients using multivariable Cox regression models.Results:Among the 1,089 patients included in this subgroup analysis, 93 (8.5%) patients had a recurrent ischemic stroke at 90 days. Compared with those without infarction or ICAS, patients with single infarction with ICAS (11.9% vs 1.3%, hazard ratio [HR] 6.25, 95% confidence intervals [CIs] 1.40–27.86, p = 0.02) and single infarction without ICAS (6.8% vs 1.3%, HR 4.65, 95% CI 1.05–20.64, p = 0.04) were all associated with an increased risk of ischemic stroke at 90 days. Patients with both multiple infarctions and ICAS were associated with approximately 13-fold risk of ischemic stroke at 90 days (18.0% vs 1.3%, HR 13.14, 95% CI 2.96–58.36, p < 0.001).Conclusions:The presence of multiple infarctions and ICAS were both associated with an increased risk of 90-day ischemic stroke in patients with minor stroke or TIA, while the presence of both imaging features had a combined effect.ClinicalTrials.gov identifier:NCT00979589.


2021 ◽  
pp. 239698732110585
Author(s):  
Elora Basu ◽  
Setareh Salehi Omran ◽  
Hooman Kamel ◽  
Neal S Parikh

Background Sex differences in stroke outcomes have been noted, but whether this extends to stroke recurrence is unclear. We examined sex differences in recurrent stroke using data from the Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial. Patients and methods We assessed the risk of recurrent stroke in women compared to men using data from the POINT trial. Adults >18 years old were randomized within 12 hours of onset of minor ischemic stroke or transient ischemic attack (TIA), and followed for up to 90 days for ischemic stroke, our primary outcome. We used Cox proportional hazards model adjusted for demographics and stroke risk factors to evaluate the association between sex and stroke recurrence. We used interaction term testing and prespecified subgroup analyses to determine if the association between sex and recurrent stroke differed by age (<60 versus >60 years old), locale (US versus non-US), and index event type (stroke versus TIA). Last, we evaluated whether sex modified the effect of common stroke risk factors on stroke recurrence. Results Of 4,881 POINT trial participants with minor stroke or high-risk TIA, 2,195 (45%) were women. During the 90-day follow-up period, 267 ischemic strokes occurred; 121 were in women and 146 in men. The cumulative risk of recurrent ischemic stroke was not significantly different among women (5.76%; 95% CI, 4.84%–6.85%) compared to men (5.67%; 95% CI, 4.83%–6.63%). Women were not at a different risk of recurrent ischemic stroke compared to men (hazard ratio [HR], 1.02; 95% CI, 0.80–1.30) in unadjusted models or after adjusting for covariates. However, there was a significant interaction of age with sex (P=0.04). Among patients <60 years old, there was a non-significantly lower risk of recurrent stroke in women compared to men (HR 0.66; 95% CI 0.42–1.05). Last, sex did not modify the association between common stroke risk factors and recurrent stroke risk. Discussion and Conclusion Among patients with minor stroke or TIA, the risk of recurrent ischemic stroke and the impact of common stroke risk factors did not differ between men and women.


Author(s):  
Moira K. Kapral ◽  
Ruth Hall ◽  
Jiming Fang ◽  
Peter C. Austin ◽  
Frank L. Silver ◽  
...  

AbstractBackground: Transient ischemic attack (TIA) and minor stroke are associated with a substantial risk of subsequent stroke; however, there is uncertainty about whether such patients require admission to hospital for their initial management. We used data from a clinical stroke registry to determine the frequency and predictors of hospitalization for TIA or minor stroke across the province of Ontario, Canada. Methods: The Ontario Stroke Registry collects information on a population-based sample of all patients seen in the emergency department with acute stroke or TIA in Ontario. We identified patients with minor ischemic stroke or TIA included in the registry between April 1, 2008, and March 31, 2011, and used multivariable analyses to evaluate predictors of hospitalization. Results: Our study sample included 8540 patients with minor ischemic stroke or TIA, 47.2% of whom were admitted to hospital, with a range of 37.6% to 70.3% across Ontario’s 14 local health integration network regions. Key predictors of admission were preadmission disability, vascular risk factors, presentation with weakness, speech disturbance or prolonged/persistent symptoms, arrival by ambulance, and presentation on a weekend or during periods of emergency department overcrowding. Conclusions: More than one-half of patients with minor stroke or TIA were not admitted to the hospital, and there were wide regional variations in admission patterns. Additional work is needed to provide guidance to health care workers around when to admit such patients and to determine whether discharged patients are receiving appropriate follow-up care.


Author(s):  
Anas Alrohimi ◽  
Kelvin Ng ◽  
Dar Dowlatshahi ◽  
Brian Buck ◽  
Grant Stotts ◽  
...  

ABSTRACT:Objectives:The optimal timing of anticoagulation after ischemic stroke in atrial fibrillation (AF) patients is unknown. Our aim was to demonstrate the feasibility and safety of initiating dabigatran therapy within 14 days of transient ischemic attack (TIA) or minor stroke in AF patients.Patients and Methods:A prospective, multi-center registry (NCT02415855) in patients with AF treated with dabigatran within 14 days of acute ischemic stroke/TIA (National Institutes of Health Stroke Scale (NIHSS) ≤ 3) onset. Baseline and follow-up computed tomography (CT) scans were assessed for hemorrhagic transformation (HT) and graded by using European Cooperative Acute Stroke Study criteria.Results:One hundred and one patients, with a mean age of 72.4 ± 11.5 years, were enrolled. Median infarct volume was 0 ml. Median time from index event onset to dabigatran initiation was 2 days, and median baseline NIHSS was 1. Pre-treatment HT was present in seven patients. No patients developed symptomatic HT. On the day 7 CT scan, HT was present in six patients (one progressing from baseline hemorrhagic infarction type 1). Infarct volume was a predictor of incident HT (odds ratio = 1.063 [1.020–1.107], p < 0.003). All six (100%) patients with new/progressive HT were functionally independent (modified Rankin Scale (mRS) = 0–2) at 30 days, which was similar to those without HT (90%, p = 0.422). Recurrent ischemic events occurred within 30 days in four patients, two of which were associated with severe disability and death (mRS 5 and 6, respectively).Conclusion:Early dabigatran treatment did not precipitate symptomatic HT after minor stroke. Asymptomatic HT was associated with larger baseline infarct volumes. Early recurrent ischemic events may be clinically more important.


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