scholarly journals RETRACTED ARTICLE: Dual versus mono antiplatelet therapy for acute non- cardio embolic ischemic stroke or transient ischemic attack, an efficacy and safety analysis - updated meta-analysis

BMC Neurology ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Christessa Emille Que Albay ◽  
Frederick Gavril D. Leyson ◽  
Federick C. Cheng

Abstract Background New evidence on the efficacy and safety of dual antiplatelet therapy for secondary stroke prevention have been realized in the recent years. An updated meta analysis was done to determine the effect of the various dual antiplatelets vs aspirin alone on recurrence rate of ischemic stroke, cardiovascular morbidity and mortality, and its safety profile as reported through major bleeding. Methods PubMed, Cochrane and Science Direct data bases were utilized, RCTs evaluating dual antiplatelet vs mono antiplatelet therapy for acute ischemic stroke or transient ischemic attack within < 72 h from ictus were searched up to July 2019. Risk ratio at 95% confidence intervals were calculated to evaluate stroke recurrence, cardiac events and mortality, and major bleeding. Results Sixteen randomized controlled trials with a population of 28, 032 patients were pooled into a meta-analysis. Dual antiplatelet therapy was significantly superior over mono antiplatelet therapy in the reduction of stroke (RR 0.75, 95% CI:0.68–0.83, p value< 0.00001) and composite events namely cardiovascular morbidity and mortality (0.73 95% CI: 0.65–0.82, p value < 0.00001), while bleeding events were noted to be not significant (1.22 95% CI: 0.87–1.70, p value = 0.25). Conclusion In acute non-cardioembolic ischemic strokes or those who have suffered a transient ischemic attack, dual antiplatelet therapy was associated with efficacy in stroke recurrence and composite cardiac events, with a non-significant risk of major bleeding.

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):  
Kirtipal Bhatia ◽  
Vardhmaan Jain ◽  
Devika Aggarwal ◽  
Muthiah Vaduganathan ◽  
Sameer Arora ◽  
...  

Background and Purpose: Antiplatelet therapy is key for preventing thrombotic events after transient ischemic attack or ischemic stroke. Although the role of aspirin is well established, there is emerging evidence for the role of short-term dual antiplatelet therapy (DAPT) in preventing recurrent stroke. Methods: We conducted a systematic review and study-level meta-analyses of randomized controlled trials comparing outcomes of early initiation of short-term DAPT (aspirin+P2Y12 inhibitor for up to 3 months) versus aspirin alone in patients with acute stroke or transient ischemic attack. Primary efficacy outcome was risk of recurrent stroke and primary safety outcome was incidence of major bleeding. Secondary outcomes studied were risk of any ischemic stroke, hemorrhagic stroke, major adverse cardiovascular events, and all-cause death. Pooled risk ratios (RRs) and CIs were calculated using a random-effects model. Results: Four trials with a total of 21 459 patients were included. As compared to aspirin alone, DAPT had a lower risk of recurrent stroke (RR, 0.76 [95% CI, 0.68–0.83]; P <0.001; I 2 = 0%) but a higher risk of major bleeding events (RR, 2.22 [95% CI, 1.14–4.34], P =0.02, I 2 = 46.5%). Patients receiving DAPT had a lower risk of major adverse cardiovascular events (RR, 0.76 [95% CI, 0.69–0.84], P <0.001, I 2 = 0%) and recurrent ischemic events (RR, 0.74 [95% CI, 0.67–0.82], P <0.001, I 2 = 0%). Conclusions: As compared to aspirin alone, short-term DAPT within 24 hours of high-risk transient ischemic attack or mild-moderate ischemic stroke reduces the risk of recurrent stroke at the expense of higher risk of major bleeding.


Stroke ◽  
2019 ◽  
Vol 50 (11) ◽  
pp. 3135-3140 ◽  
Author(s):  
Dimitrios Sagris ◽  
Georgios Georgiopoulos ◽  
Kalliopi Perlepe ◽  
Konstantinos Pateras ◽  
Eleni Korompoki ◽  
...  

Background and Purpose— It is unclear whether treatment with anticoagulants or antiplatelets is the optimal strategy in patients with stroke or transient ischemic attack of undetermined cause and patent foramen ovale that is not percutaneously closed. We aimed to perform a systematic review and meta-analysis of randomized controlled trials to compare anticoagulant or antiplatelet treatment in this population. Methods— We searched PubMed until July 16, 2019 for trials comparing anticoagulants and antiplatelet treatment in patients with stroke/transient ischemic attack and medically treated patent foramen ovale using the terms: “cryptogenic or embolic stroke of undetermined source” and “stroke or cerebrovascular accident or transient ischemic attack” and “patent foramen ovale or patent foramen ovale or paradoxical embolism” and “trial or study” and “antithrombotic or anticoagulant or antiplatelet.” The outcomes assessed were stroke recurrence, major bleeding, and the composite end point of stroke recurrence or major bleeding. We used 3 random-effects models: (1) a reference model based on the inverse variance method with the Sidik and Jonkman heterogeneity estimator; (2) a strict model, implementing the Hartung and Knapp method; and (3) a commonly used Bayesian model with a prior that assumes moderate to large between-study variance. Results— Among 112 articles identified in the literature search, 5 randomized controlled trials were included in the meta-analysis (1720 patients, mean follow-up 2.3±0.5 years). Stroke recurrence occurred at a rate of 1.73 per 100 patient-years in anticoagulant-assigned patients and 2.39 in antiplatelet-assigned patients (hazard ratio, 0.68; 95% CI, 0.32–1.48 for the Sidik and Jonkman estimator). Major bleeding occurred at a rate of 1.16 per 100 patient-years in anticoagulant-assigned patients and 0.68 in antiplatelet-assigned patients (hazard ratio, 1.61; 95% CI, 0.72–3.59 for the Sidik and Jonkman estimator). The composite outcome occurred in 52 anticoagulant-assigned and 54 antiplatelet-assigned patients (odds ratio, 1.05; 95% CI, 0.65–1.70 for the Sidik and Jonkman estimator). Conclusions— We cannot exclude a large reduction of stroke recurrence in anticoagulant-assigned patients compared with antiplatelet-assigned, without significant differences in major bleeding. An adequately powered randomized controlled trial of a non–vitamin K antagonist versus aspirin is warranted.


Stroke ◽  
2021 ◽  
Author(s):  
Nina A. Hilkens ◽  
Ale Algra ◽  
Hans Christoph Diener ◽  
Philip M. Bath ◽  
László Csiba ◽  
...  

Background and Purpose: Lifelong treatment with antiplatelet drugs is recommended following a transient ischemic attack or ischemic stroke. Bleeding complications may offset the benefit of antiplatelet drugs in patients at increased risk of bleeding and low risk of recurrent ischemic events. We aimed to investigate the net benefit of antiplatelet treatment according to an individuals’ bleeding risk. Methods: We pooled individual patient data from 6 randomized clinical trials (CAPRIE [Clopidogrel Versus Aspirin in Patients at Risk of Ischemic Events], ESPS-2 [European Stroke Prevention Study-2], MATCH [Management of Atherothrombosis With Clopidogrel in High-Risk Patients], CHARISMA [Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance], ESPRIT [European/Australasian Stroke Prevention in Reversible Ischemia Trial], and PRoFESS [Prevention Regimen for Effectively Avoiding Second Strokes]) investigating antiplatelet therapy in the subacute or chronic phase after noncardioembolic transient ischemic attack or stroke. Patients were stratified into quintiles according to their predicted risk of major bleeding with the S 2 TOP-BLEED score. The annual risk of major bleeding and recurrent ischemic events was assessed per quintile for 4 scenarios: (1) aspirin monotherapy, (2) aspirin-clopidogrel versus aspirin or clopidogrel monotherapy, (3) aspirin-dipyridamole versus clopidogrel, and (4) aspirin versus clopidogrel. Net benefit was calculated for the second, third, and fourth scenario. Results: Thirty seven thousand eighty-seven patients were included in the analyses. Both risk of major bleeding and recurrent ischemic events increased over quintiles of predicted bleeding risk, but risk of ischemic events was consistently higher (eg, from 0.7%/y (bottom quintile) to 3.2%/y (top quintile) for major bleeding on aspirin and from 2.5%/y to 10.2%/y for risk of ischemic events on aspirin). Treatment with aspirin-clopidogrel led to more major bleedings (0.9%–1.7% per year), than reduction in ischemic events (ranging from 0.4% to 0.9/1.0% per year) across all quintiles. There was no clear preference for either aspirin-dipyridamole or clopidogrel according to baseline bleeding risk. Conclusions: Among patients with a transient ischemic attack or ischemic stroke included in clinical trials of antiplatelet therapy, the risk of recurrent ischemic events and of major bleeding increase in parallel. Antiplatelet treatment cannot be individualized solely based on bleeding risk assessment.


2018 ◽  
Vol 3 (2) ◽  
pp. 107-116 ◽  
Author(s):  
Yingying Yang ◽  
Mengyuan Zhou ◽  
Xi Zhong ◽  
Yongjun Wang ◽  
Xingquan Zhao ◽  
...  

ObjectiveRecent years have seen new evidence on the efficacy and safety of dual antiplatelet therapy for secondary stroke prevention. We updated a meta-analysis of randomised controlled trials evaluating dual antiplatelet versus monotherapy for patients with acute non-cardioembolic ischaemic stroke (IS) or transient ischaemic attack (TIA).MethodsWe searched PubMed and identified randomised controlled trials evaluating dual antiplatelet versus monotherapy for acute non-cardioembolic IS or TIA within 3 days of ictus up to May 2018. Risk ratio (RR) with 95% CI were calculated using random effects models. Clinical endpoints included stroke recurrence, composite vascular events and major bleeding.Results18 randomised controlled trials including 15 515 patients were pooled in the meta-analysis. When compared with monotherapy among patients with acute IS or TIA, dual antiplatelet therapy reduced the risk of stroke recurrence (RR 0.69; 95% CI 0.61 to 0.78; p<0.001) and composite vascular events (RR 0.72; 95% CI 0.64 to 0.80; p<0.001). Dual therapy was associated with a significant increase in the risk of major bleeding (RR 1.77; 95% CI 1.09 to 2.87; p=0.02) when all trial data were combined. However, when all previous trials before the completion of the POINT trial were analysed, dual antiplatelet versus monotherapy was not associated with a significant increase in the risk of major bleeding (RR 1.46; 95% CI 0.77 to 2.75; p=0.25).ConclusionsAmong patients with acute non-cardioembolic IS or TIA within 3 days of ictus, dual antiplatelet therapy was associated with a reduction in stroke recurrence, and composite vascular events, when compared with monotherapy. However, a significant increase in the risk of major bleeding was observed.


Stroke ◽  
2022 ◽  
Author(s):  
Luciano A. Sposato ◽  
Seemant Chaturvedi ◽  
Cheng-Yang Hsieh ◽  
Carlos A. Morillo ◽  
Hooman Kamel

Atrial fibrillation (AF) can be newly detected in approximately one-fourth of patients with ischemic stroke and transient ischemic attack without previously recognized AF. We present updated evidence supporting that AF detected after stroke or transient ischemic attack (AFDAS) may be a distinct clinical entity from AF known before stroke occurrence (known atrial fibrillation). Data suggest that AFDAS can arise from the interplay of cardiogenic and neurogenic forces. The embolic risk of AFDAS can be understood as a gradient defined by the prevalence of vascular comorbidities, the burden of AF, neurogenic autonomic changes, and the severity of atrial cardiopathy. The balance of existing data indicates that AFDAS has a lower prevalence of cardiovascular comorbidities, a lower degree of cardiac abnormalities than known atrial fibrillation, a high proportion (52%) of very brief (<30 seconds) AF paroxysms, and is more frequently associated with insular brain infarction. These distinctive features of AFDAS may explain its recently observed lower associated risk of stroke than known atrial fibrillation. We present an updated ad-hoc meta-analysis of randomized clinical trials in which the association between prolonged cardiac monitoring and reduced risk of ischemic stroke was nonsignificant (incidence rate ratio, 0.90 [95% CI, 0.71–1.15]). These findings highlight that larger and sufficiently powered randomized controlled trials of prolonged cardiac monitoring assessing the risk of stroke recurrence are needed. Meanwhile, we call for further research on AFDAS and stroke recurrence, and a tailored approach when using prolonged cardiac monitoring after ischemic stroke or transient ischemic attack, focusing on patients at higher risk of AFDAS and, more importantly, at higher risk of cardiac embolism.


Stroke ◽  
2021 ◽  
Author(s):  
Mohammad Anadani ◽  
Adam de Havenon ◽  
Nils Henninger ◽  
Lindsey Kuohn ◽  
Brian Mac Grory ◽  
...  

Background and Purpose: Dual antiplatelet therapy has been shown to reduce the risk of recurrent stroke in patients with minor stroke or transient ischemic attack. However, whether the effect of dual antiplatelet therapy is modified by pretreatment antiplatelet status is unclear. Methods: This is a post hoc analysis of the POINT trial (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke). Patients were divided into 2 groups based on pretreatment antiplatelet use. The primary outcome was ischemic stroke within 90 days of randomization. Results: We included 4881 patients of whom 41% belonged to the no pretreatment antiplatelet. Ischemic stroke occurred in 6% and 5% in the antiplatelet pretreatment and no antiplatelet pretreatment, respectively. Antiplatelet pretreatment was not associated with the risk of ischemic stroke (adjusted hazard ratio, 1.05 [95% CI, 0.81–137]) or risk of major hemorrhage (hazard ratio, 1.10 [95% CI, 0.55–2.21]; P =0.794). The effect of dual antiplatelet therapy on recurrent ischemic stroke risk was not different in patients who were on antiplatelet before randomization (adjusted hazard ratio, 0.69 [95% CI, 0.50–0.94]) as opposed to those who were not (adjusted hazard ratio, 0.75 [95% CI, 0.50–1.12]), P for interaction = 0.685. Conclusions: In patients with minor stroke and high-risk transient ischemic attack, dual antiplatelet therapy reduces the risk of ischemic stroke regardless of premorbid antiplatelet use.


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