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      Comparative outcomes of heart failure among existent classes of anti-diabetic agents: a network meta-analysis of 171,253 participants from 91 randomized controlled trials

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          Abstract

          Background

          The cardiovascular (CV) safety in terms of heart failure among different classes of treatment remains largely unknown. We sought to assess the comparative effect of these agents on heart failure outcomes.

          Methods

          This study was registered in the International Prospective Register of Systematic Reviews (CRD 42016042063). MEDLINE, EMBASE, and the Cochrane Library Central Register of Controlled Trials were searched. For the primary outcomes reported previously, studies between Jan 1, 1980 and June 30, 2016 were screened, and subsequently updated till Jan 24, 2019. We performed network meta-analysis to obtain estimates for the outcomes of heart failure, in particular by rankograms for ranking of heart failure risk as well as by pairwise comparisons among all classes of anti-diabetic medications.

          Results

          A total of 91 trials were included, among which were 171,253 participants and 4163 reported cases of heart failure events. As for rankograms, the surface under the cumulative ranking curves (SUCRA) of sodium-glucose co-transporters 2 and thiazolidinediones were 93.4% and 4.3%, respectively, signifying the lowest and highest risk of heart failure, respectively. As for pairwise comparisons in the network, sodium-glucose co-transporters 2 were significantly superior to insulin (OR: 0.75, 95% CI 0.62–0.91), dipeptidyl peptidase 4 inhibitors (OR: 0.68, 95% CI 0.59–0.78), glucagon-like peptide-1 receptor agonists (OR: 0.65, 95% CI 0.54–0.78), and thiazolidinediones (OR: 0.46, 95% CI 0.27–0.77) in terms of heart failure risk. Furthermore, in an exploratory analysis among subjects with underlying heart failure or at risk of heart failure, the superiority of sodium-glucose co-transporters 2 was still significant.

          Conclusions

          In terms of heart failure risk, sodium-glucose co-transporters 2 were the most favorable option among all classes of anti-diabetic medications.

          Electronic supplementary material

          The online version of this article (10.1186/s12933-019-0853-x) contains supplementary material, which is available to authorized users.

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          Most cited references48

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          Evaluation of inconsistency in networks of interventions.

          The assumption of consistency, defined as agreement between direct and indirect sources of evidence, underlies the increasingly popular method of network meta-analysis. No evidence exists so far regarding the extent of inconsistency in full networks of interventions or the factors that control its statistical detection. In this paper we assess the prevalence of inconsistency from data of 40 published networks of interventions involving 303 loops of evidence. Inconsistency is evaluated in each loop by contrasting direct and indirect estimates and by employing an omnibus test of consistency for the entire network. We explore whether different effect measures for dichotomous outcomes are associated with differences in inconsistency, and evaluate whether different ways to estimate heterogeneity affect the magnitude and detection of inconsistency. Inconsistency was detected in from 2% to 9% of the tested loops, depending on the effect measure and heterogeneity estimation method. Loops that included comparisons informed by a single study were more likely to show inconsistency. About one-eighth of the networks were found to be inconsistent. The proportions of inconsistent loops do not materially change when different effect measures are used. Important heterogeneity or the overestimation of heterogeneity was associated with a small decrease in the prevalence of statistical inconsistency. The study suggests that changing the effect measure might improve statistical consistency, and that an analysis of sensitivity to the assumptions and an estimator of heterogeneity might be needed before reaching a conclusion about the absence of statistical inconsistency, particularly in networks with few studies.
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            Impact of diabetes on outcomes in patients with low and preserved ejection fraction heart failure: an analysis of the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme.

            To determine whether the risk of adverse cardiovascular (CV) outcomes associated with diabetes differs in patients with low and preserved ejection fraction (EF) heart failure (HF). We analysed outcomes in the Candesartan in Heart failure-Assessment of Reduction in Mortality and morbidity (CHARM) programme which randomized 7599 patients with symptomatic HF and a broad range of EF. The prevalence of diabetes was 28.3% in patients with preserved EF (>40%) and 28.5% in those with low EF (
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              • Article: not found

              Effects of Liraglutide on Clinical Stability Among Patients With Advanced Heart Failure and Reduced Ejection Fraction: A Randomized Clinical Trial.

              Abnormal cardiac metabolism contributes to the pathophysiology of advanced heart failure with reduced left ventricular ejection fraction (LVEF). Glucagon-like peptide 1 (GLP-1) agonists have shown cardioprotective effects in early clinical studies of patients with advanced heart failure, irrespective of type 2 diabetes status.
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                Author and article information

                Contributors
                y2kchocolate@163.com
                hexin_sysu@163.com
                ngurep@21cn.com
                zhangshzh@mail2.sysu.edu.cn
                zhongxb3@foxmail.com
                luochuf@mail.sysu.edu.cn
                dujiaoshou7890@126.com
                hejiangui@163.com
                zhuangxd3@mail.sysu.edu.cn
                liaoxinx@mail.sysu.edu.cn
                Journal
                Cardiovasc Diabetol
                Cardiovasc Diabetol
                Cardiovascular Diabetology
                BioMed Central (London )
                1475-2840
                8 April 2019
                8 April 2019
                2019
                : 18
                : 47
                Affiliations
                [1 ]GRID grid.412615.5, Department of Cardiology, , First Affiliated Hospital of Sun Yat-Sen University, ; No. 58 Zhong Shan 2nd Road, Guangzhou, 510080 China
                [2 ]ISNI 0000 0001 2360 039X, GRID grid.12981.33, NHC Key Laboratory of Assisted Circulation, , Sun Yat-Sen University, ; Guangzhou, China
                [3 ]ISNI 0000 0004 1757 6882, GRID grid.452505.3, Administrative Office of Clinical Trial Center, , Guangzhou Hui-Ai Hospital, ; Guangzhou, China
                Article
                853
                10.1186/s12933-019-0853-x
                6454617
                30961600
                4bac93ec-f44c-40d2-b7f1-8cadaf075d8a
                © 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
                : 20 February 2019
                : 2 April 2019
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100009330, Medical Science and Technology Foundation of Guangdong Province;
                Award ID: 2016A020220007
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 81600206
                Award ID: 81870195
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100003453, Natural Science Foundation of Guangdong Province;
                Award ID: 2016A030310140
                Award ID: 20160903
                Award Recipient :
                Categories
                Review
                Custom metadata
                © The Author(s) 2019

                Endocrinology & Diabetes
                cardiovascular,meta-analysis,heart failure,diabetes,agent
                Endocrinology & Diabetes
                cardiovascular, meta-analysis, heart failure, diabetes, agent

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