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      Intravenous Thrombolysis for Acute Ischemic Stroke in Patients Receiving Antiplatelet Therapy: A Systematic Review and Meta‐analysis of 19 Studies

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          Abstract

          Background

          The safety and long‐term outcome of systemic thrombolysis in patients receiving antiplatelet medications remain subjects of great clinical significance. The objective of this meta‐analysis was to determine how prestroke antiplatelet therapy affects the risks and benefits of intravenous thrombolysis in patients with acute ischemic stroke.

          Methods and Results

          A dual‐reviewer search was conducted in PubMed and EMBASE databases through November 2015, from which 19 studies involving a total of 108 588 patients with acute ischemic stroke were identified based on preset inclusion criteria. Information on study designs, patient characteristics, exposures, outcomes, and adjusting confounders was extracted, and estimates were combined by using random‐effects models. The pooled crude estimates suggested that taking long‐term antiplatelet medications was associated with higher odds of symptomatic intracranial hemorrhage (odds ratio [OR] 1.70, 95% CI 1.47–1.97) and death ( OR 1.46, 95% CI 1.22–1.75) and lower odds of favorable functional outcomes ( OR 0.86, 95% CI 0.80–0.93). However, the combined confounder‐adjusted results only confirmed a relatively weak positive association between prior antiplatelet therapy and symptomatic intracranial hemorrhage ( OR 1.21, 95% CI 1.02–1.44) and demonstrated no significant relationship between antiplatelet therapy and the other 2 outcomes (favorable outcome OR 1.09, 95% CI 0.96–1.24; death OR 1.02, 95% CI 0.98–1.07). Subgroup analyses revealed that the associations between prestroke antiplatelet therapy and outcomes were dependent on time and antiplatelet agents.

          Conclusions

          Patients with acute ischemic stroke receiving long‐term antiplatelet medications were associated with greater risks of developing symptomatic intracranial hemorrhage after systemic thrombolysis. However, the overall independent association between prestroke antiplatelet therapy and unfavorable outcomes or mortality was insignificant.

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          Most cited references23

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          Guidelines for Management of Ischaemic Stroke and Transient Ischaemic Attack 2008

          This article represents the update of the European Stroke Initiative Recommendations for Stroke Management. These guidelines cover both ischaemic stroke and transient ischaemic attacks, which are now considered to be a single entity. The article covers referral and emergency management, Stroke Unit service, diagnostics, primary and secondary prevention, general stroke treatment, specific treatment including acute management, management of complications, and rehabilitation.
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            Recombinant tissue plasminogen activator for acute ischaemic stroke: an updated systematic review and meta-analysis

            Summary Background Recombinant tissue plasminogen activator (rt-PA, alteplase) improved functional outcome in patients treated soon after acute ischaemic stroke in randomised trials, but licensing is restrictive and use varies widely. The IST-3 trial adds substantial new data. We therefore assessed all the evidence from randomised trials for rt-PA in acute ischaemic stroke in an updated systematic review and meta-analysis. Methods We searched for randomised trials of intravenous rt-PA versus control given within 6 h of onset of acute ischaemic stroke up to March 30, 2012. We estimated summary odds ratios (ORs) and 95% CI in the primary analysis for prespecified outcomes within 7 days and at the final follow-up of all patients treated up to 6 h after stroke. Findings In up to 12 trials (7012 patients), rt-PA given within 6 h of stroke significantly increased the odds of being alive and independent (modified Rankin Scale, mRS 0–2) at final follow-up (1611/3483 [46·3%] vs 1434/3404 [42·1%], OR 1·17, 95% CI 1·06–1·29; p=0·001), absolute increase of 42 (19–66) per 1000 people treated, and favourable outcome (mRS 0–1) absolute increase of 55 (95% CI 33–77) per 1000. The benefit of rt-PA was greatest in patients treated within 3 h (mRS 0–2, 365/896 [40·7%] vs 280/883 [31·7%], 1·53, 1·26–1·86, p<0·0001), absolute benefit of 90 (46–135) per 1000 people treated, and mRS 0–1 (283/896 [31·6%] vs 202/883 [22·9%], 1·61, 1·30–1·90; p<0·0001), absolute benefit 87 (46–128) per 1000 treated. Numbers of deaths within 7 days were increased (250/2807 [8·9%] vs 174/2728 [6·4%], 1·44, 1·18–1·76; p=0·0003), but by final follow-up the excess was no longer significant (679/3548 [19·1%] vs 640/3464 [18·5%], 1·06, 0·94–1·20; p=0·33). Symptomatic intracranial haemorrhage (272/3548 [7·7%] vs 63/3463 [1·8%], 3·72, 2·98–4·64; p<0·0001) accounted for most of the early excess deaths. Patients older than 80 years achieved similar benefit to those aged 80 years or younger, particularly when treated early. Interpretation The evidence indicates that intravenous rt-PA increased the proportion of patients who were alive with favourable outcome and alive and independent at final follow-up. The data strengthen previous evidence to treat patients as early as possible after acute ischaemic stroke, although some patients might benefit up to 6 h after stroke. Funding UK Medical Research Council, Stroke Association, University of Edinburgh, National Health Service Health Technology Assessment Programme, Swedish Heart-Lung Fund, AFA Insurances Stockholm (Arbetsmarknadens Partners Forsakringsbolag), Karolinska Institute, Marianne and Marcus Wallenberg Foundation, Research Council of Norway, Oslo University Hospital.
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              Risk factors for intracranial hemorrhage in acute ischemic stroke patients treated with recombinant tissue plasminogen activator: a systematic review and meta-analysis of 55 studies.

              Recombinant tissue plasminogen activator (rtPA) is an effective treatment for acute ischemic stroke but is associated with an increased risk of intracranial hemorrhage (ICH). We sought to identify the risk factors for ICH with a systematic review of the published literature. We searched for studies of rtPA-treated stroke patients that reported an association between a variable measured before rtPA infusion and clinically important ICH (parenchymal ICH or ICH associated with clinical deterioration). We calculated associations between baseline variables and ICH with random-effect meta-analyses. We identified 55 studies that measured 43 baseline variables in 65 264 acute ischemic stroke patients. Post-rtPA ICH was associated with higher age (odds ratio, 1.03 per year; 95% confidence interval, 1.01-1.04), higher stroke severity (odds ratio, 1.08 per National Institutes of Health Stroke Scale point; 95% confidence interval, 1.06-1.11), and higher glucose (odds ratio, 1.10 per mmol/L; 95% confidence interval, 1.05-1.14). There was approximately a doubling of the odds of ICH with the presence of atrial fibrillation, congestive heart failure, renal impairment, previous antiplatelet agents, leukoaraiosis, and a visible acute cerebral ischemic lesion on pretreatment brain imaging. Little of the variation in the sizes of the associations among different studies was explained by the source of the cohort, definition of ICH, or degree of adjustment for confounding variables. Individual baseline variables were modestly associated with post-rtPA ICH. Prediction of post-rtPA ICH therefore is likely to be difficult if based on single clinical or imaging factors alone. These observational data do not provide a reliable method for the individualization of treatment according to predicted ICH risk.
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                Author and article information

                Journal
                J Am Heart Assoc
                J Am Heart Assoc
                10.1002/(ISSN)2047-9980
                JAH3
                ahaoa
                Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
                John Wiley and Sons Inc. (Hoboken )
                2047-9980
                20 May 2016
                May 2016
                : 5
                : 5 ( doiID: 10.1002/jah3.2016.5.issue-5 )
                : e003242
                Affiliations
                [ 1 ] Department of Hypertension and Vascular DiseaseThe First Affiliated Hospital of Sun Yat‐Sen University GuangzhouChina
                [ 2 ] Department of CardiologyThe First Affiliated Hospital of Sun Yat‐Sen University GuangzhouChina
                [ 3 ] Department of GeriatricsThe First Affiliated Hospital of Sun Yat‐Sen University GuangzhouChina
                Author notes
                [*] [* ] Correspondence to: Jun Tao, MD, PhD, Department of Hypertension and Vascular Disease, The First Affiliated Hospital of Sun Yat‐Sen University, 58 Zhong Shan 2nd Road, Guangzhou 510080, China. E‐mail: taojungz123@ 123456163.com
                Article
                JAH31527
                10.1161/JAHA.116.003242
                4889195
                27207999
                9ffd0162-c223-494a-b4b5-69bd72560ae5
                © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

                This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 12 January 2016
                : 08 April 2016
                Page count
                Pages: 14
                Funding
                Funded by: 973 Program
                Award ID: 2013CB531200
                Funded by: National Nature Science Foundation of China
                Award ID: 31530023
                Award ID: 81100201
                Award ID: 31370941
                Award ID: 81200249
                Categories
                Original Research
                Original Research
                Stroke
                Custom metadata
                2.0
                jah31527
                May 2016
                Converter:WILEY_ML3GV2_TO_NLMPMC version:4.8.9 mode:remove_FC converted:27.05.2016

                Cardiovascular Medicine
                meta‐analysis,plasminogen activators,stroke,ischemic stroke,quality and outcomes,meta analysis

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