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      Comparative effectiveness and safety of DOACs vs. VKAs in treatment of left ventricular thrombus- a meta-analysis update

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          Abstract

          Background and objective

          Left ventricular thrombus (LVT) formation in patients with acute myocardial infarction (AMI) or cardiomyopathies is not uncommon. The optimal oral anticoagulation therapy for resolving LVT has been under intense debate. Vitamin K antagonists (VKAs) remain the anticoagulant of choice for this condition, according to practice guidelines. Evidence supporting the use of direct oral anticoagulants (DOACs) in the management of LVT continues to grow. We performed a systematic review and meta-analysis to compare the efficacy and safety of DOACs versus VKAs.

          Methods

          A comprehensive literature search was carried out in PubMed, Cochrane Library, Web of Science, Embase, and Scopus databases in July 2023. The efficacy outcomes of this study were thrombus resolution, ischemic stroke, systemic embolism, stroke/systemic embolism, all-cause mortality, and adverse cardiovascular events. The safety outcomes were any bleeding, major bleeding, and intracranial hemorrhage. A total of twenty-seven eligible studies were included in the meta-analysis. Data were analyzed utilizing Stata software version 15.1.

          Results

          There was no significant difference between DOACs and VKAs with regard to LVT resolution (RR = 1.00, 95% CI 0.95–1.05, P = 0.99). In the overall analysis, DOACs significantly reduced the risk of stroke (RR = 0.74, 95% CI 0.57–0.96, P = 0.021), all-cause mortality (RR = 0.70, 95% CI 0.57–0.86, P = 0.001), any bleeding (RR = 0.75, 95% CI 0.61–0.92, P = 0.006) and major bleeding (RR = 0.67, 95% CI 0.52–0.85, P = 0.001) when compared to VKAs. Meanwhile, in the sub-analysis examining randomized controlled trials (RCTs), the aforementioned outcomes no longer differed significantly between the DOACs and VKAs groups. The incidences of systemic embolism (RR = 0.81, 95% CI 0.54–1.22, P = 0.32), stroke/systemic embolism (RR = 0.85, 95% CI 0.72–1.00, P = 0.056), intracranial hemorrhage (RR = 0.59, 95% CI 0.23–1.54, P = 0.28), and adverse cardiovascular events (RR = 0.99, 95% CI 0.63–1.56, P = 0.92) were comparable between the DOACs and VKAs groups. A subgroup analysis showed that patients treated with rivaroxaban had a significantly lower risk of stroke (RR = 0.24, 95% CI 0.08–0.72, P = 0.011) than those in the VKAs group.

          Conclusion

          With non-inferior efficacy and superior safety, DOACs are promising therapeutic alternatives to VKAs in the treatment of LVT. Further robust investigations are warranted to confirm our findings.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s12959-024-00585-9.

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          Most cited references51

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          The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration

          Systematic reviews and meta-analyses are essential to summarise evidence relating to efficacy and safety of healthcare interventions accurately and reliably. The clarity and transparency of these reports, however, are not optimal. Poor reporting of systematic reviews diminishes their value to clinicians, policy makers, and other users. Since the development of the QUOROM (quality of reporting of meta-analysis) statement—a reporting guideline published in 1999—there have been several conceptual, methodological, and practical advances regarding the conduct and reporting of systematic reviews and meta-analyses. Also, reviews of published systematic reviews have found that key information about these studies is often poorly reported. Realising these issues, an international group that included experienced authors and methodologists developed PRISMA (preferred reporting items for systematic reviews and meta-analyses) as an evolution of the original QUOROM guideline for systematic reviews and meta-analyses of evaluations of health care interventions. The PRISMA statement consists of a 27-item checklist and a four-phase flow diagram. The checklist includes items deemed essential for transparent reporting of a systematic review. In this explanation and elaboration document, we explain the meaning and rationale for each checklist item. For each item, we include an example of good reporting and, where possible, references to relevant empirical studies and methodological literature. The PRISMA statement, this document, and the associated website (www.prisma-statement.org/) should be helpful resources to improve reporting of systematic reviews and meta-analyses.
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            Rivaroxaban versus warfarin in nonvalvular atrial fibrillation.

            The use of warfarin reduces the rate of ischemic stroke in patients with atrial fibrillation but requires frequent monitoring and dose adjustment. Rivaroxaban, an oral factor Xa inhibitor, may provide more consistent and predictable anticoagulation than warfarin. In a double-blind trial, we randomly assigned 14,264 patients with nonvalvular atrial fibrillation who were at increased risk for stroke to receive either rivaroxaban (at a daily dose of 20 mg) or dose-adjusted warfarin. The per-protocol, as-treated primary analysis was designed to determine whether rivaroxaban was noninferior to warfarin for the primary end point of stroke or systemic embolism. In the primary analysis, the primary end point occurred in 188 patients in the rivaroxaban group (1.7% per year) and in 241 in the warfarin group (2.2% per year) (hazard ratio in the rivaroxaban group, 0.79; 95% confidence interval [CI], 0.66 to 0.96; P<0.001 for noninferiority). In the intention-to-treat analysis, the primary end point occurred in 269 patients in the rivaroxaban group (2.1% per year) and in 306 patients in the warfarin group (2.4% per year) (hazard ratio, 0.88; 95% CI, 0.74 to 1.03; P<0.001 for noninferiority; P=0.12 for superiority). Major and nonmajor clinically relevant bleeding occurred in 1475 patients in the rivaroxaban group (14.9% per year) and in 1449 in the warfarin group (14.5% per year) (hazard ratio, 1.03; 95% CI, 0.96 to 1.11; P=0.44), with significant reductions in intracranial hemorrhage (0.5% vs. 0.7%, P=0.02) and fatal bleeding (0.2% vs. 0.5%, P=0.003) in the rivaroxaban group. In patients with atrial fibrillation, rivaroxaban was noninferior to warfarin for the prevention of stroke or systemic embolism. There was no significant between-group difference in the risk of major bleeding, although intracranial and fatal bleeding occurred less frequently in the rivaroxaban group. (Funded by Johnson & Johnson and Bayer; ROCKET AF ClinicalTrials.gov number, NCT00403767.).
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              2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines.

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                Author and article information

                Contributors
                chentongshuai@163.com
                198762000778@email.sdu.edu.cn
                Journal
                Thromb J
                Thromb J
                Thrombosis Journal
                BioMed Central (London )
                1477-9560
                1 March 2024
                1 March 2024
                2024
                : 22
                : 23
                Affiliations
                [1 ]GRID grid.452402.5, ISNI 0000 0004 1808 3430, National Key Laboratory for Innovation and Transformation of Luobing Theory; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences; Department of Cardiology, , Qilu Hospital of Shandong University, ; 107 Wen Hua Xi Road, Jinan, 250012 China
                [2 ]Department of Cardiology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, ( https://ror.org/0207yh398) 758 Hefei Road, Qingdao, 266035 Shandong China
                Article
                585
                10.1186/s12959-024-00585-9
                10905864
                38429631
                a78b4ca9-9a3a-42a4-a0a7-f749c3c40761
                © The Author(s) 2024

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. 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 in a credit line to the data.

                History
                : 8 August 2023
                : 22 January 2024
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 82270331
                Funded by: Qingdao Key Clinical Specialty Elite Discipline
                Award ID: QDZDZK-2022008
                Funded by: FundRef http://dx.doi.org/10.13039/100019558, Qingdao Key Health Discipline Development Fund;
                Categories
                Review
                Custom metadata
                © BioMed Central Ltd., part of Springer Nature 2024

                Cardiovascular Medicine
                Cardiovascular Medicine

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