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      Effect of antiplatelet therapy on cardiovascular and kidney outcomes in patients with chronic kidney disease: a systematic review and meta-analysis

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          Abstract

          Background

          The benefits and risks of antiplatelet therapy for patients with chronic kidney disease (CKD) remain controversial. We undertook a systematic review and meta-analysis to investigate the effects of antiplatelet therapy on major clinical outcomes.

          Methods

          We systematically searched MEDLINE, Embase, and the Cochrane Library for trials published before April 2019 without language restriction. We included rrandomized controlled trials that involved adults with CKD and compared antiplatelet agents with controls.

          Results

          Fifty eligible trials that included at least one event were identified, providing data for 27773patients with CKD, including 4518 major cardiovascular events and 1962 all-cause deaths. Antiplatelet therapy produced a 15% (OR, 0.85; 95% CI 0.74–0.94) reduction in the odds of major cardiovascular events ( P = 0.002), a 48% reduction for access failure events (OR, 0.52; 95% CI, 0.31–0.73), but had no significantly effect on all-cause death (OR, 0.87; 95% CI, 0.71–1.01) or kidney failure events (OR, 0.87; 95% CI, 0.32–1.55). Adverse events were significantly increased by antiplatelet therapy, including major (OR, 1.33; 95% CI, 1.11–1.59) or minor bleeding (OR, 1.66; 95% CI, 1.27–2.05). Among every 1000 persons with CKD treated with antiplatelet therapy for 12 months, 23 major cardiovascular events will be prevented while nine major bleeding events will occur.

          Conclusions

          Major prevention with antiplatelet agents (cardiovascular events and access failure), might outweigh the risk of bleeding, and there seemed to be an overall net benefit. Individual evaluation and careful monitoring are required.

          Electronic supplementary material

          The online version of this article (10.1186/s12882-019-1499-3) contains supplementary material, which is available to authorized users.

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          Most cited references75

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          Improved tests for a random effects meta-regression with a single covariate.

          The explanation of heterogeneity plays an important role in meta-analysis. The random effects meta-regression model allows the inclusion of trial-specific covariates which may explain a part of the heterogeneity. We examine the commonly used tests on the parameters in the random effects meta-regression with one covariate and propose some new test statistics based on an improved estimator of the variance of the parameter estimates. The approximation of the distribution of the newly proposed tests is based on some theoretical considerations. Moreover, the newly proposed tests can easily be extended to the case of more than one covariate. In a simulation study, we compare the tests with regard to their actual significance level and we consider the log relative risk as the parameter of interest. Our simulation study reflects the meta-analysis of the efficacy of a vaccine for the prevention of tuberculosis originally discussed in Berkey et al. The simulation study shows that the newly proposed tests are superior to the commonly used test in holding the nominal significance level. Copyright 2003 John Wiley & Sons, Ltd.
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            Relation between kidney function, proteinuria, and adverse outcomes.

            The current staging system for chronic kidney disease is based primarily on estimated glomerular filtration rate (eGFR) with lower eGFR associated with higher risk of adverse outcomes. Although proteinuria is also associated with adverse outcomes, it is not used to refine risk estimates of adverse events in this current system. To determine the association between reduced GFR, proteinuria, and adverse clinical outcomes. Community-based cohort study with participants identified from a province-wide laboratory registry that includes eGFR and proteinuria measurements from Alberta, Canada, between 2002 and 2007. There were 920 985 adults who had at least 1 outpatient serum creatinine measurement and who did not require renal replacement treatment at baseline. Proteinuria was assessed by urine dipstick or albumin-creatinine ratio (ACR). All-cause mortality, myocardial infarction, and progression to kidney failure. The majority of individuals (89.1%) had an eGFR of 60 mL/min/1.73 m(2) or greater. Over median follow-up of 35 months (range, 0-59 months), 27 959 participants (3.0%) died. The fully adjusted rate of all-cause mortality was higher in study participants with lower eGFRs or heavier proteinuria. Adjusted mortality rates were more than 2-fold higher among individuals with heavy proteinuria measured by urine dipstick and eGFR of 60 mL/min/1.73 m(2) or greater, as compared with those with eGFR of 45 to 59.9 mL/min/1.73 m(2) and normal protein excretion (rate, 7.2 [95% CI, 6.6-7.8] vs 2.9 [95% CI, 2.7-3.0] per 1000 person-years, respectively; rate ratio, 2.5 [95% CI, 2.3-2.7]). Similar results were observed when proteinuria was measured by ACR (15.9 [95% CI, 14.0-18.1] and 7.0 [95% CI, 6.4-7.6] per 1000 person-years for heavy and absent proteinuria, respectively; rate ratio, 2.3 [95% CI, 2.0-2.6]) and for the outcomes of hospitalization with acute myocardial infarction, end-stage renal disease, and doubling of serum creatinine level. The risks of mortality, myocardial infarction, and progression to kidney failure associated with a given level of eGFR are independently increased in patients with higher levels of proteinuria.
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              Maximum Likelihood Approaches to Variance Component Estimation and to Related Problems

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                Author and article information

                Contributors
                425541151@qq.com
                564381781@qq.com
                kunle6609@126.com
                jichenglv75@gmail.com
                13911530708@163.com
                +0086-13910736475 , chen_yipu@163.com
                Journal
                BMC Nephrol
                BMC Nephrol
                BMC Nephrology
                BioMed Central (London )
                1471-2369
                7 August 2019
                7 August 2019
                2019
                : 20
                : 309
                Affiliations
                [1 ]ISNI 0000 0004 0369 153X, GRID grid.24696.3f, Division of Nephrology, , Beijing Anzhen Hospital, Capital Medical University, ; No. 2, Anzhen Street, Chaoyang District, Beijing, China
                [2 ]ISNI 0000 0004 1798 4018, GRID grid.263452.4, Division of Nephrology, , Shanxi Medical University Second Hospital, Shanxi Kidney Disease Institute, ; No.382, Wuyi Road, Xinghualing Distirct, Taiyuan, China
                [3 ]Division of Nephrology, Peking University First Hospital, Peking University Institute of Nephrology, No.8, Xishiku Street, Xicheng District, Beijing, China
                Article
                1499
                10.1186/s12882-019-1499-3
                6686545
                31390997
                01effa4d-0415-4871-b6f3-c6a67551d877
                © The Author(s). 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 26 July 2018
                : 29 July 2019
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100004480, Natural Science Foundation of Shanxi Province;
                Award ID: No. 201701D221173
                Award Recipient :
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2019

                Nephrology
                antiplatelet therapy,chronic kidney disease,cardiovascular events,meta-analysis
                Nephrology
                antiplatelet therapy, chronic kidney disease, cardiovascular events, meta-analysis

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