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      Association of Elevated Blood Pressure Levels with Outcomes in Acute Ischemic Stroke Patients Treated with Intravenous Thrombolysis: A Systematic Review and Meta-Analysis

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          Abstract

          Background and Purpose

          Although arbitrary blood pressure (BP) thresholds exist for acute ischemic stroke (AIS) patients eligible for intravenous thrombolysis (IVT), current international recommendations lack clarity on the impact of mean pre- and post-IVT BP levels on clinical outcomes.

          Methods

          Eligible studies involving IVT-treated AIS patients were identified that reported the association of mean systolic BP (SBP) or diastolic BP levels before and after IVT with the following outcomes: 3-month favorable functional outcome (modified Rankin Scale [mRS] scores of 0–1) and 3-month functional independence (mRS scores of 0–2), 3-month mortality and symptomatic intracranial hemorrhage (sICH). Unadjusted analyses of standardized mean differences and adjusted analyses of studies reporting odds ratios (OR adj) per 10 mm Hg BP increment were performed using random-effects models.

          Results

          We identified 26 studies comprising 56,513 patients. Higher pre- ( P=0.02) and posttreatment ( P=0.006) SBP levels were observed in patients with sICH. Patients with 3-month functional independence had lower post-treatment ( P<0.001) SBP whereas trended towards lower pre-treatment ( P=0.06) SBP. In adjusted analyses, elevated pre- (OR adj, 1.08; 95% confidence interval [CI], 1.01 to 1.16) and post-treatment (OR adj, 1.13; 95% CI, 1.01 to 1.25) SBP levels were associated with increased likelihood of sICH. Increasing pre- (OR adj, 0.91; 95% CI, 0.84 to 0.98) and post-treatment (OR adj, 0.70; 95% CI, 0.57 to 0.87) SBP values were also related to lower odds of 3-month functional independence.

          Conclusions

          We found that elevated BP levels adversely impact AIS outcomes in patients receiving IVT. Future randomized-controlled clinical trials will provide definitive data on the aforementioned association.

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          Most cited references34

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          A Nonparametric “Trim and Fill” Method of Accounting for Publication Bias in Meta-Analysis

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            Blood pressure and clinical outcomes in the International Stroke Trial.

            Among patients with acute stroke, high blood pressure is often associated with poor outcome, although the reason is unclear. We analyzed data from the International Stroke Trial (IST) to explore the relationship between systolic blood pressure (SBP), subsequent clinical events over the next 2 weeks, and functional outcome at 6 months in patients with acute stroke. We included in the analysis 17 398 patients from IST with confirmed ischemic stroke. A single measurement of SBP was made immediately before randomization. Clinical events within 14 days of randomization were recorded: recurrent ischemic stroke, symptomatic intracranial hemorrhage, death resulting from presumed cerebral edema, fatal coronary heart disease, and death. Survival and dependency were assessed at 6 months. Outcomes were adjusted for age, sex, clinical stroke syndrome, time to randomization, consciousness level, atrial fibrillation, and treatment allocation (aspirin, unfractionated heparin, both, or neither). A U-shaped relationship was found between baseline SBP and both early death and late death or dependency: early death increased by 17.9% for every 10 mm Hg below 150 mm Hg (P<0.0001) and by 3.8% for every 10 mm Hg above 150 mm Hg (P=0.016). The rate of recurrent ischemic stroke within 14 days increased by 4.2% for every 10-mm Hg increase in SBP (P=0.023); this association was present in both fatal and nonfatal recurrence. Death resulting from presumed cerebral edema was independently associated with high SBP (P=0.004). No relationship between symptomatic intracranial hemorrhage and SBP was seen. Low SBP was associated with a severe clinical stroke (total anterior circulation syndrome) and an excess of deaths from coronary heart disease (P=0.002). Both high blood pressure and low blood pressure were independent prognostic factors for poor outcome, relationships that appear to be mediated in part by increased rates of early recurrence and death resulting from presumed cerebral edema in patients with high blood pressure and increased coronary heart disease events in those with low blood pressure. The occurrence of symptomatic intracranial hemorrhage within 14 days was independent of SBP.
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              The impact of outcome reporting bias in randomised controlled trials on a cohort of systematic reviews.

              To examine the prevalence of outcome reporting bias-the selection for publication of a subset of the original recorded outcome variables on the basis of the results-and its impact on Cochrane reviews. A nine point classification system for missing outcome data in randomised trials was developed and applied to the trials assessed in a large, unselected cohort of Cochrane systematic reviews. Researchers who conducted the trials were contacted and the reason sought for the non-reporting of data. A sensitivity analysis was undertaken to assess the impact of outcome reporting bias on reviews that included a single meta-analysis of the review primary outcome. More than half (157/283 (55%)) the reviews did not include full data for the review primary outcome of interest from all eligible trials. The median amount of review outcome data missing for any reason was 10%, whereas 50% or more of the potential data were missing in 70 (25%) reviews. It was clear from the publications for 155 (6%) of the 2486 assessable trials that the researchers had measured and analysed the review primary outcome but did not report or only partially reported the results. For reports that did not mention the review primary outcome, our classification regarding the presence of outcome reporting bias was shown to have a sensitivity of 88% (95% CI 65% to 100%) and specificity of 80% (95% CI 69% to 90%) on the basis of responses from 62 trialists. A third of Cochrane reviews (96/283 (34%)) contained at least one trial with high suspicion of outcome reporting bias for the review primary outcome. In a sensitivity analysis undertaken for 81 reviews with a single meta-analysis of the primary outcome of interest, the treatment effect estimate was reduced by 20% or more in 19 (23%). Of the 42 meta-analyses with a statistically significant result only, eight (19%) became non-significant after adjustment for outcome reporting bias and 11 (26%) would have overestimated the treatment effect by 20% or more. Outcome reporting bias is an under-recognised problem that affects the conclusions in a substantial proportion of Cochrane reviews. Individuals conducting systematic reviews need to address explicitly the issue of missing outcome data for their review to be considered a reliable source of evidence. Extra care is required during data extraction, reviewers should identify when a trial reports that an outcome was measured but no results were reported or events observed, and contact with trialists should be encouraged.
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                Author and article information

                Journal
                J Stroke
                J Stroke
                JOS
                Journal of Stroke
                Korean Stroke Society
                2287-6391
                2287-6405
                January 2019
                31 January 2019
                : 21
                : 1
                : 78-90
                Affiliations
                [a ]Department of Neurology, West Virginia University-Charleston Division, Charleston, WV, USA
                [b ]Department of Neurology, Karolinska University Hospital, Stockholm, Sweden
                [c ]Second Department of Neurology, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, Greece
                [d ]Department of Neurology, University of Ioannina School of Medicine, Ioannina, Greece
                [e ]Department of Neurology, University of Tennessee Health Science Center, Memphis, TN, USA
                [f ]First Cardiology Clinic, Hippokration Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
                [g ]Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece
                [h ]First Department of Internal Medicine, Hypertension Excellence Center, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
                [i ]Department of Neurology and Neurogeriatry, Johannes Wesling Medical Center, Ruhr University Bochum, Minden, Germany
                Author notes
                Correspondence: Georgios Tsivgoulis Second Department of Neurology, National and Kapodistrian University of Athens, School of Medicine, Iras 39, Gerakas Attikis, Athens 15344, Greece Tel: +30-6937178635 Fax: +30-2105832471 E-mail: gtsivou@ 123456med.uoa.gr
                Article
                jos-2018-02369
                10.5853/jos.2018.02369
                6372893
                30732443
                54678f9b-0e70-446b-ba0c-a2c23e220fbc
                Copyright © 2019 Korean Stroke Society

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 25 August 2018
                : 23 November 2018
                : 23 November 2018
                Categories
                Original Article

                blood pressure,stroke,thrombolytic therapy,intracranial hemorrhages,outcome assessment

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