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      Percutaneous Left Atrial Appendage Occlusion in Comparison to Non‐Vitamin K Antagonist Oral Anticoagulant Among Patients With Atrial Fibrillation

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          Abstract

          Background

          This study aimed to compare percutaneous left atrial appendage occlusion (LAAO) with non‐vitamin K antagonist oral anticoagulants among patients with atrial fibrillation.

          Methods and Results

          Using a US administrative database, 562 850 patients with atrial fibrillation were identified, among whom 8397 were treated with LAAO and 554 453 were treated with non‐vitamin K antagonist oral anticoagulants between March 13, 2015 and December 31, 2018. Propensity score overlap weighting was used to balance baseline characteristics. The primary outcome was a composite end point of ischemic stroke or systemic embolism, major bleeding, and all‐cause mortality. The mean age was 76.4±7.6 years; 280 097 (49.8%) were female. Mean follow‐up was 1.5±1.0 years. LAAO was associated with no significant difference in the risk of the primary composite end point (hazard ratio [HR], 0.93 [0.84–1.03]), or the secondary outcomes including ischemic stroke/systemic embolism (HR, 1.07 [0.81–1.41]), and intracranial bleeding (HR, 1.08 [0.72–1.61]). LAAO was associated with a higher risk of major bleeding (HR, 1.22 [1.05–1.42], P=0.01) and a lower risk of mortality (HR, 0.73 [0.64–0.84], P<0.001). The lower risk of mortality associated with LAAO was most pronounced in patients with a prior history of intracranial bleeding.

          Conclusions

          In comparison to non‐vitamin K antagonist oral anticoagulants, LAAO was associated with no significant difference in the risk of the composite outcome and a lower risk of mortality, which suggests LAAO might be a reasonable option in select patients with atrial fibrillation. The observation of higher bleeding risk associated with LAAO highlights the need to optimize postprocedural antithrombotic regimens as well as systematic efforts to assess and address bleeding predispositions.

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          Most cited references38

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          A Proportional Hazards Model for the Subdistribution of a Competing Risk

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            Sensitivity Analysis in Observational Research: Introducing the E-Value.

            Sensitivity analysis is useful in assessing how robust an association is to potential unmeasured or uncontrolled confounding. This article introduces a new measure called the "E-value," which is related to the evidence for causality in observational studies that are potentially subject to confounding. The E-value is defined as the minimum strength of association, on the risk ratio scale, that an unmeasured confounder would need to have with both the treatment and the outcome to fully explain away a specific treatment-outcome association, conditional on the measured covariates. A large E-value implies that considerable unmeasured confounding would be needed to explain away an effect estimate. A small E-value implies little unmeasured confounding would be needed to explain away an effect estimate. The authors propose that in all observational studies intended to produce evidence for causality, the E-value be reported or some other sensitivity analysis be used. They suggest calculating the E-value for both the observed association estimate (after adjustments for measured confounders) and the limit of the confidence interval closest to the null. If this were to become standard practice, the ability of the scientific community to assess evidence from observational studies would improve considerably, and ultimately, science would be strengthened.
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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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                Author and article information

                Contributors
                yao.xiaoxi@mayo.edu
                Journal
                J Am Heart Assoc
                J Am Heart Assoc
                10.1002/(ISSN)2047-9980
                JAH3
                ahaoa
                Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
                John Wiley and Sons Inc. (Hoboken )
                2047-9980
                29 September 2022
                04 October 2022
                : 11
                : 19 ( doiID: 10.1002/jah3.v11.19 )
                : e027001
                Affiliations
                [ 1 ] Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery Mayo Clinic Rochester MN
                [ 2 ] Department of Cardiovascular Medicine Mayo Clinic Rochester MN
                [ 3 ] Section of Cardiovascular Medicine, Department of Health Policy and Management, and the Center for Outcomes Research and Evaluation Yale University School of Medicine New Haven CT
                [ 4 ] Predictive Analytics and Comparative Effectiveness (PACE) Center, Institute for Clinical Research and Health Policy Studies, Tufts Medical Center/Tufts University School of Medicine Boston MA
                [ 5 ] Department of Neurology Tufts Medical Center/Tufts University School of Medicine Boston MA
                [ 6 ] Division of Gastroenterology and Hepatology, Department of Medicine Mayo Clinic Scottsdale AZ
                [ 7 ] Department of Neurology Mayo Clinic Rochester MN
                [ 8 ] OptumLabs Minnetonka MN
                [ 9 ] Delta Airlines Atlanta GA
                Author notes
                [*] [* ]Correspondence to: Xiaoxi Yao, PhD, Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, 200 First St SW, Rochester, MN 55905. Email: yao.xiaoxi@ 123456mayo.edu
                Author information
                https://orcid.org/0000-0002-4308-0456
                https://orcid.org/0000-0003-4981-4868
                https://orcid.org/0000-0003-2046-127X
                https://orcid.org/0000-0002-9205-5070
                https://orcid.org/0000-0003-2770-0691
                https://orcid.org/0000-0003-3847-0959
                https://orcid.org/0000-0001-5605-900X
                https://orcid.org/0000-0002-0037-0373
                https://orcid.org/0000-0001-9906-7106
                Article
                JAH37858 JAHA/2022/027001-T
                10.1161/JAHA.121.027001
                9673739
                36172961
                adf8b392-0212-4a31-bb70-fb45003b52f9
                © 2022 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                Page count
                Figures: 3, Tables: 14, Pages: 44, Words: 6616
                Funding
                Funded by: National Institutes of Health , doi 10.13039/100000002;
                Funded by: National Institute on Aging , doi 10.13039/100000049;
                Award ID: R01AG062436
                Categories
                Original Research
                Original Research
                Health Services and Outcomes Research
                Custom metadata
                2.0
                04 October 2022
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.2.0 mode:remove_FC converted:17.10.2022

                Cardiovascular Medicine
                atrial fibrillation,bleeding,left atrial appendage occlusion,oral anticoagulant,stroke,ischemic stroke,intracranial hemorrhage,quality and outcomes,anticoagulants

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