Original Article| Volume 81, ISSUE 4, P385-389, April 2023

Long-term outcome and risk factors associated with events in patients with atrial fibrillation treated with oral anticoagulants: The ASSAF-K registry

Published:September 12, 2022DOI:


      • Real-world oral anti-coagulant treatment status was clarified.
      • The event rate with direct anti-coagulants was significantly lower than warfarin.
      • Adverse events tended to be lower with direct oral anticoagulants than warfarin.



      Oral anticoagulant therapy for atrial fibrillation (AF) has changed dramatically. Direct oral anticoagulant (DOAC) therapy is administered by general practitioners and specialists. However, the beneficial long-term effects and safety of DOACs have not been well investigated in real-world clinical practice.


      The ASSAF-K (a study of the safety and efficacy of OAC therapy in the treatment of AF in Kanagawa), a prospective, multi-center, observational study, was conducted to clarify patient characteristics, status of OAC treatment, long-term outcomes, and adverse events, including cerebrovascular disease, bleeding, and death.


      A total of 4014 patients were enrolled (hospital: 2500 cases; clinic: 1514 cases). The number of patients in the final dataset was 3367 (mean age, 72.6 ± 10.0 years; males, 66.3 %). CHA2DS2-VASc and HAS-BLED scores were 3.0 ± 1.6 and 2.2 ± 1.0, respectively. The risk factors of the primary composite outcome (all-cause death, serious bleeding events, cerebral hemorrhage, and stroke) were higher age, lower body mass index, lower diastolic blood pressure, lower creatine clearance, history of heart failure, history of stroke, and medication of anti-platelet agents. The event-free rates of the primary composite outcome with DOACs, warfarin, and without OACs were 92.7 %, 88.0 %, and 87.4 %, respectively. The event rate of DOACs was significantly lower than that of warfarin [HR 0.63 (95 % CI 0.48–0.81)], and similar results were observed after adjustment for AF stroke risk score [HR 0.70 (95 % CI 0.54–0.90)]. Serious bleeding events tended to occur less frequently with DOACs compared with warfarin [unadjusted HR 0.53 (95 % CI 0.31–0.91), adjusted HR 0.61 (95 % CI 0.33–1.11)].


      This multi-center registry demonstrated the long-term outcome in patients with AF treated with and without OACs and suggests that DOAC therapy is safe and beneficial in hospitals and clinics.

      Graphical abstract


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        • Schnabel R.B.
        • Yin X.
        • Gona P.
        • Larson M.G.
        • Beiser A.S.
        • McManus D.D.
        • 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
        • Inoue H.
        • Fujiki A.
        • Origasa H.
        • Ogawa S.
        • Okumura K.
        • Kubota I.
        • et al.
        Prevalence of atrial fibrillation in the general population of Japan: an analysis based on periodic health examination.
        Int J Cardiol. 2009; 137: 102-107
        • Santhanakrishnan R.
        • Wang N.
        • Larson M.G.
        • Magnani J.W.
        • McManus D.D.
        • Lubitz S.A.
        • et al.
        Atrial fibrillation begets heart failure and vice versa: temporal associations and differences in preserved versus reduced ejection fraction.
        Circulation. 2016; 133: 484-492
        • 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
        • Ruff C.T.
        • Giugliano R.P.
        • Braunwald E.
        • Hoffman E.B.
        • Deenadayalu N.
        • Ezekowitz M.D.
        • et al.
        Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials.
        Lancet. 2014; 383: 955-962
        • Chatterjee S.
        • Sardar P.
        • Biondi-Zoccai G.
        • Kumbhani D.J.
        New oral anticoagulants and the risk of intracranial hemorrhage: traditional and bayesian meta-analysis and mixed treatment comparison of randomized trials of new oral anticoagulants in atrial fibrillation.
        JAMA Neurol. 2013; 70: 1486-1490
        • January C.T.
        • Wann L.S.
        • Calkins H.
        • Chen L.Y.
        • Cigarroa J.E.
        • Cleveland Jr., J.C.
        • et al.
        2019 AHA/ACC/HRS focused update of the 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 clinical practice guidelines and the Heart Rhythm Society in collaboration with the Society of Thoracic Surgeons.
        Circulation. 2019; 140: e125-e151
        • Hindricks G.
        • Potpara T.
        • Dagres N.
        • Arbelo E.
        • Bax J.J.
        • Blomström-Lundqvist C.
        • et al.
        2020 ESC guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the european Association of Cardio-Thoracic Surgery (EACTS).
        Eur Heart J. 2021; 42: 373-498
        • Akao M.
        • Chun Y.H.
        • Wada H.
        • Esato M.
        • Hashimoto T.
        • Abe M.
        • et al.
        Current status of clinical background of patients with atrial fibrillation in a community-based survey: the fushimi AF registry.
        J Cardiol. 2013; 61: 260-266
        • Okumura Y.
        • Yokoyama K.
        • Matsumoto N.
        • Tachibana E.
        • Kuronuma K.
        • Oiwa K.
        • et al.
        Current use of direct oral anticoagulants for atrial fibrillation in Japan: findings from the SAKURA AF registry.
        J Arrhythm. 2017; 33: 289-296
        • Okumura K.
        • Tomita H.
        • Nakai M.
        • Kodani E.
        • Akao M.
        • Suzuki S.
        • et al.
        Risk factors associated with ischemic stroke in Japanese patients with nonvalvular atrial fibrillation.
        JAMA Netw Open. 2020; 3e202881
        • Hatori Y.
        • Sakai H.
        • Kunishima T.
        • Hatori N.
        • Chen L.
        • Ishigami T.
        • et al.
        Rationale and design of ASSAF-K (a study of the safety and efficacy of anticoagulant therapy in the treatment of atrial fibrillation in Kanagawa).
        J Arrhythm. 2017; 33: 111-116
        • Lip G.Y.H.
        • Nieuwlaat R.
        • Pisters R.
        • Lane D.A.
        • Crijns H.J.G.M.
        Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation.
        Chest. 2010; 137: 263-272
        • 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
        • Wang K.L.
        • Lip G.Y.
        • Lin S.J.
        • Chiang C.E.
        Non-vitamin K antagonist oral anticoagulants for stroke prevention in asian patients with nonvalvular atrial fibrillation: meta-analysis.
        Stroke. 2015; 46: 2555-2561
        • Xue Z.
        • Zhang H.
        Non–vitamin K antagonist oral anticoagulants versus warfarin in asians with atrial fibrillation meta-analysis of randomized trials and real-world studies.
        Stroke. 2019; 50: 2819-2828
        • Yamashita Y.
        • Uozumi R.
        • Hamatani Y.
        • Esaton M.
        • Chun Y.-H.
        • Tsuji H.
        • et al.
        Current status and outcomes of direct oral anticoagulant use in real-world atrial fibrillation patients - fushimi AF registry.
        Circ J. 2017; 81: 1278-1285
        • Okumura Y.
        • Yokoyama K.
        • Matsumoto N.
        • Tachibana E.
        • Kuronuma K.
        • Oiwa K.
        • et al.
        Three-year clinical outcomes associated with warfarin vs. Direct oral anticoagulant use among japanese patients with atrial fibrillation - findings from the SAKURA AF registry.
        Circ J. 2018; 82: 2500-2509
        • Rohla M.
        • Weiss T.W.
        • Pecen L.
        • Patti G.
        • Siller-Matula J.M.
        • Schnabel R.B.
        • et al.
        Risk factors for thromboembolic and bleeding events in anticoagulated patients with atrial fibrillation: the prospective, multicentre observational PREvention oF thromboembolic events - european registry in atrial fibrillation (PREFER in AF).
        BMJ Open. 2019; 9e022478