scholarly journals Ticagrelor vs Clopidogrel in addition to Aspirin in minor ischemic stroke/ transient ischemic attack—Protocol for a systematic review and network meta-analysis

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 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):  
Zi-Xiao Li ◽  
Yunyun Xiong ◽  
Hong-Qiu Gu ◽  
Marc Fisher ◽  
Ying Xian ◽  
...  

Background and purpose: We performed a systemic review and meta-analysis to elucidate the effectiveness and safety of dual antiplatelet (DAPT) therapy with P2Y12 inhibitors (clopidogrel/ticagrelor) and aspirin versus aspirin monotherapy in patients with mild ischemic stroke or high-risk transient ischemic attack. Methods: Following Preferred Reported Items for Systematic Review and Meta-Analysis standards for meta-analyses, Medline, Embase, Cochrane Central Register of Controlled Trials, and the Cochrane Library were searched for randomized controlled trials that included patients with a diagnosis of an acute mild ischemic stroke or high-risk transient ischemic attack, intervention of DAPT therapy with clopidogrel/ticagrelor and aspirin versus aspirin alone from January 2012 to July 2020. The outcomes included subsequent stroke, all-cause mortality, cardiovascular death, hemorrhage (mild, moderate, or severe), and myocardial infarction. A DerSimonian-Laird random-effects model was used to estimate pooled risk ratio (RR) and corresponding 95% CI in R package meta. We assessed the heterogeneity of data across studies with use of the Cochran Q statistic and I 2 test. Results: Four eligible trials involving 21 493 participants were included in the meta-analysis. DAPT therapy started within 24 hours of symptom onset reduced the risk of stroke recurrence by 24% (RR, 0.76 [95% CI, 0.68–0.83], I 2 =0%) but was not associated with a change in all-cause mortality (RR, 1.30 [95% CI, 0.90–1.89], I 2 =0%), cardiovascular death (RR, 1.34 [95% CI, 0.56–3.17], I 2 =0%), mild bleeding (RR, 1.25 [95% CI, 0.37–4.29], I 2 =94%), or myocardial infarction (RR, 1.45 [95% CI, 0.62–3.39], I 2 =0%). However, DAPT was associated with an increased risk of severe or moderate bleeding (RR, 2.17 [95% CI, 1.16–4.08], I 2 =41%); further sensitivity tests found that the association was limited to trials with DAPT treatment duration over 21 days (RR, 2.86 [95% CI, 1.75–4.67], I 2 =0%) or ticagrelor (RR, 2.17 [95% CI, 1.16–4.08], I 2 =37%) but not within 21 days or clopidogrel. Conclusions: In patients with noncardioembolic mild stroke or high-risk transient ischemic attack, DAPT with aspirin and clopidogrel/ticagrelor is more effective than aspirin alone for recurrent stroke prevention with a small absolute increase in the risk of severe or moderate bleeding.


Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Shima Shahjouei ◽  
Eric Koza ◽  
Durgesh Chaudhary ◽  
Neil R Holland ◽  
Venkatesh Avula ◽  
...  

Importance: Management of transient ischemic attack (TIA)and the concept of urgent TIA clinic have gained significant attention over the past years. Objective: To calculate the odds of subsequent ischemic stroke within 2, 7, 30, and 90 days and death within 90 days among the TIA patients who received acute care in a TIA clinic versus those admitted to a hospital. Data Sources: We performed a systematic review and meta-analysis of all the published TIA outcome studies. Included studies were obtained by searching Medline, Web of Science, Scopus, All EBM reviews series, International Clinical Trial Registry Platform (ICTRP), Trip database, and CINAHL, last updated in March 2020, irrespective of the study design, document type, or language. Study Selection: We accepted both the classic time-based definition of TIA and the new tissue-based definition and studies with a combined record of TIA and minor ischemic stroke patients. We excluded studies with a diagnosis of index TIA event after ischemic stroke occurrence, low suspicious for TIA, TIA acute care in settings other than an outpatient clinic or hospital, multicentric studies, or duplicate reports of the same database. Data Extraction and Synthesis: The study was conducted and reported according to PRISMA, MOOSE, and EQUATOR guidelines. Critical appraisal and methodological quality were conducted by ROBINS-E tool. Data were pooled under random-effects models. Results: Systematic review yielded to 19,547 reports, of which titles and abstracts of 9,113 reports were screened. The overall subsequent ischemic stroke odds ratios were estimated by meta-analyses as follows: 4 studies within 2 days with 1,829 patients (OR: 0.93, 95% CI: -0.52-2.38), 5 studies within 7 days with 1,801 patients (OR: 0.68, 95% CI: -0.73-2.08), 4 studies within 30 days with 1,768 patients (OR:1.01, 95% CI: -0.72 - 2.73), and 6 studies within 90 days with 2,319 population (OR: 0.94, 95% CI: 0.22-1.66). The 90-day risk of death by analyzing 3 studies, 1162 patients, was calculated as OR:1.29, 95% CI: 0.76-3.34. Conclusion and Relevance: Hospital management of TIA patients in the acute phase may not be associated with a lower risk of stroke and death compared with urgent outpatient management.


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