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Dual versus mono antiplatelet therapy for acute non-cardioembolic ischaemic stroke or transient ischaemic attack: a systematic review and meta-analysis.

ABSTRACT: Recent 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).We 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.18 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).Among 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.

SUBMITTER: Yang Y

PROVIDER: S-EPMC6047341 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Dual versus mono antiplatelet therapy for acute non-cardioembolic ischaemic stroke or transient ischaemic attack: a systematic review and meta-analysis.

Yang Yingying Y Zhou Mengyuan M Zhong Xi X Wang Yongjun Y Zhao Xingquan X Liu Liping L Wang Yilong Y

Stroke and vascular neurology 20180626 2

<h4>Objective</h4>Recent 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).<h4>Methods</h4>We searched PubMed and identified randomised controlled trials evaluating dual antiplatelet versus monotherapy for acute non-cardioemb ...[more]

PMID: 30022798

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Project description:IntroductionAntiplatelet therapy combining aspirin and clopidogrel is considered to be a key intervention for acute ischaemic minor stroke (AIMS) and transient ischaemic attack (TIA). However, the interindividual variability in response to clopidogrel resulting from the polymorphisms in clopidogrel metabolism-related genes has greatly limited its efficacy. To date, there are no reports on individualised antiplatelet therapy for AIMS and TIA based on the genetic testing and clinical features. Therefore, we conduct this randomised controlled trial to validate the hypothesis that the individualised antiplatelet therapy selected on the basis of a combination of genetic information and clinical features would lead to better clinical outcomes compared with the standard care based only on clinical features in patients with AIMS or TIA.Methods and analysisThis trial will recruit 2382 patients with AIMS or TIA who meet eligibility criteria. Patients are randomly assigned in a 1:1 ratio to pharmacogenetic group and standard group. Both groups receive a loading dose of 300 mg aspirin and 300 mg clopidogrel on day 1, followed by 100 mg aspirin per day on days 2-365. The P2Y12 receptor antagonist is selected by the clinician according to the genetic information and clinical features for pharmacogenetic group and clinical features for the standard group on days 2-21. The primary efficacy endpoint is a new stroke event (ischaemic or haemorrhagic) that happens within 1 year. The secondary efficacy endpoint is analysed as the individual or composite outcomes of the new clinical vascular event (ischaemic stroke, haemorrhagic stroke, myocardial infarction or vascular death). Baseline characteristics and outcomes after treatment will be evaluated.Ethics and disseminationThis protocol has been approved by the ethics committee of Yangpu Hospital, Tongji University School of Medicine (No. LL-2018-KY-012). We will submit the results of this trial for publication in a peer-reviewed journal.Trial registration numberChiCTR1800019911; Pre-results.

Project description:To examine the comparative efficacy and safety of different antiplatelet regimens in patients with prior non-cardioembolic ischaemic stroke or transient ischaemic attack.Systematic review and network meta-analysis.As on 31 March 2015, all randomised controlled trials that investigated the effects of antiplatelet agents in the long-term (≥ 3 months) secondary prevention of non-cardioembolic transient ischaemic attack or ischaemic stroke were searched and identified.The primary outcome measure of efficacy was serious vascular events (non-fatal stroke, non-fatal myocardial infarction and vascular death). The outcome measure of safety was any bleeding.A total of 36 randomised controlled trials (82,144 patients) were included. Network meta-analysis showed that cilostazol was significantly more effective than clopidogrel (OR 0.77, 95% credible interval 0.60-0.98) and low-dose (75-162 mg daily) aspirin (0.69, 0.55-0.86) in the prevention of serious vascular events. Aspirin (50 mg daily) plus dipyridamole (400 mg daily) and clopidogrel reduced the risk of serious vascular events compared with low-dose aspirin; however, the difference was not statistically significant. Furthermore, low-dose aspirin was as effective as higher daily doses. Cilostazol was associated with a significantly lower bleeding risk than most of the other regimens. Moreover, aspirin plus clopidogrel was associated with significantly more haemorrhagic events than other regimens. Direct comparisons showed similar results as the network meta-analysis.Cilostazol was significantly more effective than aspirin and clopidogrel alone in the long-term prevention of serious vascular events in patients with prior non-cardioembolic ischaemic stroke or transient ischaemic attack. Cilostazol was associated with a significantly lower bleeding risk than low-dose aspirin (75-162 mg daily) and aspirin (50 mg daily) plus dipyridamole (400 mg daily). Low-dose aspirin was as effective as higher daily doses. However, further large, randomised, controlled, head-to-head trials are needed, especially in non-Asian ethnic groups.

Project description:OBJECTIVE:To assess the effectiveness and safety of dual agent antiplatelet therapy combining clopidogrel and aspirin to prevent recurrent thrombotic and bleeding events compared with aspirin alone in patients with acute minor ischaemic stroke or transient ischaemic attack (TIA). DESIGN:Systematic review and meta-analysis of randomised, placebo controlled trials. DATA SOURCES:Medline, Embase, Cochrane Central Register of Controlled Trials, Cochrane Library, ClinicalTrials.gov, WHO website, PsycINFO, and grey literature up to 4 July 2018. ELIGIBILITY CRITERIA FOR SELECTING STUDIES AND METHODS:Two reviewers independently screened potentially eligible studies according to predefined selection criteria and assessed the risk of bias using a modified version of the Cochrane risk of bias tool. A third team member reviewed all final decisions, and the team resolved disagreements through discussion. When reports omitted data that were considered important, clarification and additional information was sought from the authors. The analysis was conducted in RevMan 5.3 and MAGICapp based on GRADE methodology. RESULTS:Three eligible trials involving 10?447 participants were identified. Compared with aspirin alone, dual antiplatelet therapy with clopidogrel and aspirin that was started within 24 hours of symptom onset reduced the risk of non-fatal recurrent stroke (relative risk 0.70, 95% confidence interval 0.61 to 0.80, I2=0%, absolute risk reduction 1.9%, high quality evidence), without apparent impact on all cause mortality (1.27, 0.73 to 2.23, I2=0%, moderate quality evidence) but with a likely increase in moderate or severe extracranial bleeding (1.71, 0.92 to 3.20, I2=32%, absolute risk increase 0.2%, moderate quality evidence). Most stroke events, and the separation in incidence curves between dual and single therapy arms, occurred within 10 days of randomisation; any benefit after 21 days is extremely unlikely. CONCLUSIONS:Dual antiplatelet therapy with clopidogrel and aspirin given within 24 hours after high risk TIA or minor ischaemic stroke reduces subsequent stroke by about 20 in 1000 population, with a possible increase in moderate to severe bleeding of 2 per 1000 population. Discontinuation of dual antiplatelet therapy within 21 days, and possibly as early as 10 days, of initiation is likely to maximise benefit and minimise harms.

Dataset Information

Dual versus mono antiplatelet therapy for acute non-cardioembolic ischaemic stroke or transient ischaemic attack: a systematic review and meta-analysis.

Publications

Dual versus mono antiplatelet therapy for acute non-cardioembolic ischaemic stroke or transient ischaemic attack: a systematic review and meta-analysis.

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