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      Efficacy and safety of endovascular treatment versus intravenous thrombolysis for acute ischemic stroke: a meta-analysis of randomized controlled trials.

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          Abstract

          Although endovascular therapy (ET) is increasingly used in patients with moderate to severe acute ischemic stroke, its efficacy and safety remains controversial. We performed a meta-analysis aiming to compare the benefits and safety of endovascular treatment and intravenous thrombolysis in the treatment of acute ischemic stroke.

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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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            Global variation in stroke burden and mortality: estimates from monitoring, surveillance, and modelling.

            Recent improvements in the monitoring and modelling of stroke have led to more reliable estimates of stroke mortality and burden worldwide. However, little is known about the global distribution of stroke and its relations to the prevalence of cardiovascular disease risk factors and sociodemographic and economic characteristics. National estimates of stroke mortality and burden (measured in disability-adjusted life years [DALYs]) were calculated from monitoring vital statistics, a systematic review of studies that report disease surveillance, and modelling as part of the WHO Global Burden of Disease programme. Similar methods were used to generate standardised measures of the national prevalence of cardiovascular risk factors. Risk factors other than diabetes and disease burden estimates were age-adjusted and sex-adjusted to the WHO standard population. There was a ten-fold difference in rates of stroke mortality and DALY loss between the most-affected and the least-affected countries. Rates of stroke mortality and DALY loss were highest in eastern Europe, north Asia, central Africa, and the south Pacific. National per capita income was the strongest predictor of mortality and DALY loss rates (p<0.0001) even after adjustment for cardiovascular risk factors (p<0.0001). Prevalences of cardiovascular risk factors measured at a national level were generally poor predictors of national stroke mortality rates and burden, although raised mean systolic blood pressure (p=0.028) and low body-mass index (p=0.017) predicted stroke mortality, and greater prevalence of smoking predicted both stroke mortality (p=0.041) and DALY-loss rates (p=0.034). Rates of stroke mortality and burden vary greatly among countries, but low-income countries are the most affected. Current measures of the prevalence of cardiovascular risk factors at the population level poorly predict overall stroke mortality and burden and do not explain the greater burden in low-income countries.
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              Intra-arterial prourokinase for acute ischemic stroke. The PROACT II study: a randomized controlled trial. Prolyse in Acute Cerebral Thromboembolism.

              Intravenous tissue-type plasminogen activator can be beneficial to some patients when given within 3 hours of stroke onset, but many patients present later after stroke onset and alternative treatments are needed. To determine the clinical efficacy and safety of intra-arterial (IA) recombinant prourokinase (r-proUK) in patients with acute stroke of less than 6 hours' duration caused by middle cerebral artery (MCA) occlusion. PROACT II (Prolyse in Acute Cerebral Thromboembolism II), a randomized, controlled, multicenter, open-label clinical trial with blinded follow-up conducted between February 1996 and August 1998. Fifty-four centers in the United States and Canada. A total of 180 patients with acute ischemic stroke of less than 6 hours' duration caused by angiographically proven occlusion of the MCA and without hemorrhage or major early infarction signs on computed tomographic scan. Patients were randomized to receive 9 mg of IA r-proUK plus heparin (n = 121) or heparin only (n = 59). The primary outcome, analyzed by intention-to-treat, was based on the proportion of patients with slight or no neurological disability at 90 days as defined by a modified Rankin score of 2 or less. Secondary outcomes included MCA recanalization, the frequency of intracranial hemorrhage with neurological deterioration, and mortality. For the primary analysis, 40% of r-proUK patients and 25% of control patients had a modified Rankin score of 2 or less (P = .04). Mortality was 25% for the r-proUK group and 27% for the control group. The recanalization rate was 66% for the r-proUK group and 18% for the control group (P<.001). Intracranial hemorrhage with neurological deterioration within 24 hours occurred in 10% of r-proUK patients and 2% of control patients (P = .06). Despite an increased frequency of early symptomatic intracranial hemorrhage, treatment with IA r-proUK within 6 hours of the onset of acute ischemic stroke caused by MCA occlusion significantly improved clinical outcome at 90 days.
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                Author and article information

                Journal
                PLoS ONE
                PloS one
                Public Library of Science (PLoS)
                1932-6203
                1932-6203
                2013
                : 8
                : 10
                Affiliations
                [1 ] Department of Neurosurgery, Jinling Hospital, Nanjing University, Nanjing, China.
                Article
                PONE-D-13-25357
                10.1371/journal.pone.0077849
                3814965
                24204995
                1019dade-55ae-41bb-97a9-975abc944f6b
                History

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