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Comparison of clinical outcomes of edoxaban versus apixaban, dabigatran, rivaroxaban, and vitamin K antagonists in patients with atrial fibrillation in Germany: A real-world cohort study

Published:November 12, 2021DOI:https://doi.org/10.1016/j.ijcard.2021.11.008

      Highlights

      • Edoxaban is a factor X inhibitor approved for stroke prevention in AF patients.
      • The real-world data from AF patients receiving Edoxaban is limited.
      • The risk of ischemic stroke was lower for patients receiving edoxaban.
      • Major bleeding was similar for patients receiving edoxaban, apixaban, or dabigatran.
      • Edoxaban provides stroke prevention while maintaining favorable safety.

      Abstract

      Background

      The aim of the study was to compare the real-world effectiveness and safety in atrial fibrillation (AF) patients treated with edoxaban versus other oral anticoagulants (OACs) (apixaban, dabigatran, rivaroxaban, and vitamin K antagonists [VKA]) in Germany.

      Methods and results

      Using a representative database of 3.5 million statutory health-insured lives in Germany, a retrospective cohort study was conducted to examine ischemic stroke (IS) or systemic embolism (SE) and major bleeding in AF patients initiating anticoagulant therapy from January 2014 through June 2017. Inverse probability of treatment weighting using propensity score was applied for baseline covariate adjustment. Cox proportional hazards models were used to estimate the adjusted risk (hazard ratio [HR]) of each outcome comparing edoxaban versus other OACs.
      Among 21,038 patients treated with OACs, 1236 edoxaban, 6053 apixaban, 1306 dabigatran, 7013 rivaroxaban, and 5430 VKA patients were included. The adjusted combined risks of IS or SE were lower (p < 0.05) for each edoxaban pairwise comparison with other OACs (HR: 0.83 vs. apixaban, 0.60 vs. dabigatran, 0.72 vs. rivaroxaban, 0.64 vs. VKA). Edoxaban favored lower risks of major bleeding compared with rivaroxaban (HR: 0.74) and VKA (HR: 0.47). No differences in the risk of major bleeding were found between edoxaban and apixaban (p = 0.33), and between edoxaban and dabigatran (p = 0.06).

      Conclusions

      Edoxaban was associated with better effectiveness compared with other OACs in AF patients from Germany. Edoxaban also demonstrated a favorable safety profile.

      Keywords

      Abbreviations:

      Abbreviation (Description), ACEI (Angiotensin Converting Enzyme Inhibitors), AF (Atrial Fibrillation), AIDS (Acquired Immunodeficiency Syndrome), ARB (Angiotensin Receptor Blockers), DVT (Deep Vein Thrombosis), ED (Emergency Department), ESRD (End-Stage Renal Disease), GFL (Gesundheitsforen Leipzig GmbH), HCRU (Healthcare Resource Utilization), HIV (Human Immunodeficiency Virus), HR (Hazard Ratio), INR (International Normalized Ratio), IPTW (Inverse Probability Treatment Weight), IS (Ischemic Stroke), NOAC (Non-VKA Oral Anticoagulant), NSAIDs (Non-Steroidal Anti-Inflammatory Drugs), OAC (Oral Anticoagulant), PE (Pulmonary Embolism), SE (Systemic Embolism), TBI (Traumatic Brain Injury), VKA (Vitamin K Antagonists), VTE (Venous Thromboembolism)
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      References

        • Patel N.J.
        • Atti V.
        • Mitrani R.D.
        • Viles-Gonzalez J.F.
        • Goldberger J.J.
        Global rising trends of atrial fibrillation: a major public health concern.
        Heart. 2018; 104: 1989-1990
        • Wolf P.A.
        • Abbott R.D.
        • Kannel W.B.
        Atrial fibrillation as an independent risk factor for stroke: the Framingham study.
        Stroke. 1991; 22: 983-988
        • Schnabel R.B.
        • Yin X.
        • Gona P.
        • et al.
        50 year trends in atrial fibrillation prevalence, incidence, risk factors, and mortality in the Framingham heart study: a cohort study.
        Lancet. 2015; 386: 154-162
        • Kumar K.
        Overview of atrial fibrillation. UpToDate Web site. Published 2020.
        (Accessed March 11, 2021)
        • January C.T.
        • Wann L.S.
        • Alpert J.S.
        • et al.
        2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association task force on practice guidelines and the Heart Rhythm Society.
        Circulation. 2014; 130: e199-e267
        • Kirchhof P.
        • Benussi S.
        • Kotecha D.
        • et al.
        2016 ESC guidelines for the management of atrial fibrillation developed in collaboration with EACTS.
        Eur. Heart J. 2016; 37: 2893-2962
        • Zoni-Berisso M.
        • Lercari F.
        • Carazza T.
        • Domenicucci S.
        Epidemiology of atrial fibrillation: European perspective.
        Clin. Epidemiol. 2014; 6: 213-220
        • Wilke T.
        • Groth A.
        • Mueller S.
        • et al.
        Incidence and prevalence of atrial fibrillation: an analysis based on 8.3 million patients.
        Europace. 2013; 15: 486-493
        • Chan Y.-H.
        • Lee H.-F.
        • See L.-C.
        • et al.
        Effectiveness and safety of four direct oral anticoagulants in asian patients with nonvalvular atrial fibrillation.
        Chest. 2019; 156: 529-543
        • Kakkos S.K.
        • Kirkilesis G.I.
        • Tsolakis I.A.
        Editor's choice - efficacy and safety of the new oral anticoagulants dabigatran, rivaroxaban, apixaban, and edoxaban in the treatment and secondary prevention of venous thromboembolism: a systematic review and meta-analysis of phase III trials.
        Eur. J. Vasc. Endovasc. Surg. 2014; 48: 565-575
        • Schwill S.
        • Krug K.
        • Peters-Klimm F.
        • et al.
        Novel oral anticoagulants in primary care in patients with atrial fibrillation: a cross-sectional comparison before and after their introduction.
        BMC Fam. Pract. 2018; 19: 115
        • Giugliano R.P.
        • Ruff C.T.
        • Braunwald E.
        • et al.
        Edoxaban versus warfarin in patients with atrial fibrillation.
        N. Engl. J. Med. 2013; 369: 2093-2104
        • Marston X.L.
        • Wang R.
        • Yeh Y.-C.
        • et al.
        Comparison of clinical outcomes with edoxaban versus apixaban, dabigatran, rivaroxaban, and vitamin K antagonist in patients with atrial fibrillation in Germany: a real-world cohort study.
        Eur. Heart J. 2020; 41 (ehaa946. 0401)
        • Wang R.
        • Marston X.L.
        • Yeh Y.-C.
        • Zimmermann L.
        • Ye X.
        • Gao X.
        Comparison of treatment adherence and persistence with edoxaban versus apibaxan, dabigatran, rivaroxaban, and vitamin K antagonist in non-valvulvar atrial fibrillation patients in Germany: a propensity-matched cohort study.
        Value Health. 2020; 23: S106
        • Yeh Y.-C.
        • Wang R.
        • Marston X.L.
        • Zimmermann L.
        • Ye X.
        • Gao X.
        Improved adherence to anticoagulant therapy with once-daily regimen: a real-world study in patients with atrial fibrillation in Germany.
        Eur. Heart J. 2020; 41
        • Steffel J.
        • Verhamme P.
        • Potpara T.S.
        • et al.
        The 2018 european heart rhythm association practical guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation.
        Eur. Heart J. 2018; 39: 1330-1393
        • Quan H.
        • Li B.
        • Couris C.M.
        • et al.
        Updating and validating the charlson comorbidity index and score for risk adjustment in hospital discharge abstracts using data from 6 countries.
        Am. J. Epidemiol. 2011; 173: 676-682
        • Kokotailo R.A.
        • Hill M.D.
        Coding of stroke and stroke risk factors using international classification of diseases, revisions 9 and 10.
        Stroke. 2005; 36: 1776-1781
        • Lip G.Y.H.
        • Keshishian A.
        • Li X.
        • et al.
        Effectiveness and safety of oral anticoagulants among nonvalvular atrial fibrillation patients.
        Stroke. 2018; 49: 2933-2944
        • Inoue K.
        • Hirao K.
        • Aonuma K.
        • et al.
        HAS-BLED score as a predictor of bleeding complications from catheter ablation of atrial fibrillation: a subanalysis of the Japanese anti-coagulation regimen exploration in AF catheter ablation registries.
        J. Cardiol. 2020; 75: 82-89
        • Gage B.F.
        • Waterman A.D.
        • Shannon W.
        • Boechler M.
        • Rich M.W.
        • Radford M.J.
        Validation of clinical classification schemes for predicting stroke: results from the national registry of atrial fibrillation.
        JAMA. 2001; 285: 2864-2870
        • Go A.S.
        • Hylek E.M.
        • Chang Y.
        • et al.
        Anticoagulation therapy for stroke prevention in atrial fibrillation: how well do randomized trials translate into clinical practice?.
        JAMA. 2003; 290: 2685-2692
        • Lip G.Y.
        • Frison L.
        • Halperin J.L.
        • Lane D.A.
        Comparative validation of a novel risk score for predicting bleeding risk in anticoagulated patients with atrial fibrillation: the HAS-BLED (Hypertension, abnormal Renal/Liver function, stroke, bleeding history or predisposition, labile INR, elderly, Drugs/Alcohol Concomitantly) score.
        J. Am. Coll. Cardiol. 2011; 57: 173-180
        • Pisters R.
        • Lane D.A.
        • Nieuwlaat R.
        • de Vos C.B.
        • Crijns H.J.
        • Lip G.Y.
        A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey.
        Chest. 2010; 138: 1093-1100
        • Chi N.F.
        • Wang Y.
        • Chien L.N.
        • Chien S.C.
        • Ko Y.
        Health care costs and utilization of dabigatran compared with warfarin for secondary stroke prevention in patients with nonvalvular atrial fibrillation: a retrospective population study.
        Med. Care. 2018; 56: 410-415
        • Austin P.C.
        An introduction to propensity score methods for reducing the effects of confounding in observational studies.
        Multivar. Behav. Res. 2011; 46: 399-424
        • Harel Z.
        • Sholzberg M.
        • Shah P.S.
        • et al.
        Comparisons between novel oral anticoagulants and vitamin K antagonists in patients with CKD.
        J. Am. Soc. Nephrol. 2014; 25: 431-442
        • Hicks T.
        • Stewart F.
        • Eisinga A.
        NOACs versus warfarin for stroke prevention in patients with AF: a systematic review and meta-analysis.
        Open Heart. 2016; 3e000279
        • Skjøth F.
        • Larsen T.B.
        • Rasmussen L.H.
        • Lip G.Y.
        Efficacy and safety of edoxaban in comparison with dabigatran, rivaroxaban and apixaban for stroke prevention in atrial fibrillation.An indirect comparison analysis.
        Thromb. Haemost. 2014; 111: 981-988
        • Prada-Ramallal G.
        • Takkouche B.
        • Figueiras A.
        Bias in pharmacoepidemiologic studies using secondary health care databases: a scoping review.
        BMC Med. Res. Methodol. 2019; 19: 53