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Underutilization of anticoagulants in patients with nonvalvular atrial fibrillation in the era of non-vitamin K antagonist oral anticoagulants



Non-vitamin K antagonist oral anticoagulants (NOACs) are preferred over vitamin K antagonists (VKAs) as oral anticoagulant (OAC) therapy in patients with nonvalvular atrial fibrillation (NVAF). This study aimed to estimate the current status and risk factors of OAC underutilization in the NOAC era.


A cross-sectional study using nationwide claims data was conducted. Elderly patients with NVAF at an increased risk of stroke were selected as candidates for OAC therapy before the index date (July 1, 2018). The status of anticoagulant utilization on the index date and factors influencing the use of anticoagulants was investigated in these patients.


Of the 11,056 patients with NVAF who were eligible for OAC therapy, 7238 (65.5%) were receiving OAC on the index date, and 6302 (87.1%) were receiving NOACs. Patients aged ≥ 75 years had higher anticoagulant utilization than those aged 65–69 years. Among comorbid diseases, while hypertension was the most influential positive factor (odds ratio [OR] = 1.644; confidence interval [CI] = 1.445–1.869) in OAC utilization, severe renal disease was the most influential negative factor (OR = 0.289; CI = 0.200–0.416). Aspirin use had a significantly low OR (OR = 0.097; CI = 0.085–0.110) of anticoagulant use. OAC use was approximately 1.5 times higher in patients with persistent or permanent AF than in those with paroxysmal AF.


Approximately one-third of patients who are recommended anticoagulation therapy do not take OACs, even though the use of NOACs has become more common. It should be widely recognized that aspirin cannot be an alternative to OACs, and anticoagulant therapy should be actively implemented.


The prevalence of atrial fibrillation (AF) is rising worldwide due to an aging population and advances in diagnostic technology [1, 2]. In the USA, approximately 5.2 million individuals were affected by AF in 2010, and 12.1 million individuals have estimated to be affected by AF in 2030 [1, 3]. In South Korea, the prevalence of AF has been consistently increasing from 0.73% in 2006 to 1.53% in 2015 and is expected to reach 5.81% in 2060 [4]. AF is associated with a four–fivefold increased risk of ischemic stroke [5] and is known as an independent risk factor for ischemic stroke severity, recurrence, and mortality [6].

For patients with AF and an elevated CHA2DS2-VASc (congestive heart failure, hypertension, age ≥ 75 years [doubled], diabetes mellitus, prior stroke or transient ischemic attack [TIA] [doubled], vascular disease, age 65–74 years, and sex) score, oral anticoagulants (OACs) are recommended because the risk of stroke can be greatly reduced by anticoagulation therapy [7,8,9,10]. However, the underutilization of anticoagulation therapy in patients with AF has been recognized as a global health problem [11,12,13,14].

OAC therapy for patients with AF has been limited to warfarin for a long time, and insufficient OAC option has been evaluated as a risk factor for OAC underutilization [15]. However, since the introduction of non-vitamin K antagonist oral anticoagulants (NOACs) in the 2010s, a range of OACs have become available for patients with AF. Moreover, NOACs are recommended over warfarin in NOAC-eligible patients with AF as it has non-inferior or superior efficacy and lower risk of serious bleeding than warfarin [7,8,9,10].

In South Korea, NOACs were considered second-line therapy in stroke prevention after the failure of warfarin due to contraindication, sensitivity, or treatment failure until July 2015. Currently, NOACs are used as first-line therapy. After February 2016, the following NOACs have been used dabigatran, rivaroxaban, apixaban, and edoxaban.

In a previous study, the rate of anticoagulant underutilization among patients with AF in South Korea was significant. Although it has been improving every year, it is considerably high [15, 16]. Female sex, old age, medical aid, and vascular disease have been identified as risk factors for anticoagulant underutilization [15]. NOACs have excellent efficacy in stroke prevention and are clinically useful for reducing the risk of bleeding. Further, dose adjustments are not needed for NOACs. Hence, the expansion of NOAC reimbursement criteria and diversification of drug choice is expected to improve the underutilization of anticoagulation therapy.

Several studies on the underutilization of anticoagulation therapy in patients with AF have been conducted, but the use of drugs was judged roughly, and most studies were conducted during the early stages of reimbursement criteria expansion [15,16,17]. Therefore, this study aimed to evaluate the current status and risk factors of OAC underutilization through cross-sectional analysis using real-world data.


Study data

Aged Population Sample (APS) data on approximately 700,000 individuals (10% extraction rate) aged ≥ 65 years in South Korea, collected by the Health Insurance Review and Assessment Service (HIRA) in 2018 (HIRA-APS-2018-0039), were used.

The Korean Classification of Diseases-7 codes (KCD-7 codes; the Korean version of ICD-10) was used to identify patients with specific diseases or conditions. Ingredient codes were used to identify four NOACs (dabigatran, rivaroxaban, apixaban, and edoxaban), warfarin, and aspirin (“Appendix”).

The South Korean health insurance system consolidates all types of social insurance (the National Health Insurance [NHI], Medical Aid [MedAid], and Patriots & Veterans Insurance [PVI]) into a single-payer, and all citizens are obligated to subscribe to the system [18]. All types of social insurance are subject to the same benefit criteria but differ only in the patients’ paying rate of healthcare costs for copayments. The NHI covers approximately 97% of the population and imposes a duty on income, while the MedAid is a guaranteed system for low-income people and the PVI is for national veterans [18]. The Institutional Review Board of the Pusan National University approved this study (PNU IRB/2020_92_HR).

Study subjects

Patients who were primarily diagnosed with AF or atrial flutter (AFL) between January 1, 2018, and June 30, 2018, were identified. Patients with valvular heart disease were excluded. Patients with mitral stenosis or valve replacement based on KCD-7 codes were classified as patients with valvular heart disease. Among patients with nonvalvular AF (NVAF), those who had a CHA2DS2-VASc score of ≥ 2 were considered appropriate candidates for anticoagulant therapy in this study. We investigated whether the study subjects were receiving OACs on the index date (July 1, 2018) and the types of OACs they were receiving.

The following factors influencing the use of anticoagulants were investigated: age, sex, insurance type, the presence of comorbid diseases, medical institution type, region, aspirin use, and AF type. Insurance types were divided into the NHI and MedAid/PVI. Comorbid diseases included congestive heart failure, hypertension, diabetes mellitus, stroke/TIA, vascular disease, anemia, severe renal disease, and prior hemorrhage. The medical institution types were divided into tertiary hospitals, general hospitals, and primary medical institutions. The region was divided into the capital city, six metropolitan cities, and other regions.

Statistical analysis

The patients’ demographic characteristics are presented using frequency analysis and as percent, since all of them are categorical variables. The p values were determined using chi-squared tests for the anticoagulant utilization. We performed multiple logistic regression analysis to analyze the factors affecting the anticoagulant utilization. The Hosmer–Lemeshow test was used to ensure the accuracy of the goodness of fit for the models. All statistical analyses were performed using R Statistical Software (version 4.1.1; R Foundation for Statistical computing, Vienna, Austria), and the significance level was set at p < 0.05.


Subject characteristics

A total of 11,056 patients with NVAF requiring OAC therapy were included in the analysis on the index date (Fig. 1). The demographics and clinical characteristics of the study subjects are summarized in Table 1. Patients aged ≥ 75 comprised 56.0% of the study population, and the proportion of male patients was higher than that of female patients (52.0% vs. 48.0%). On the index date, 15.6% of patients were using aspirin.

Fig. 1
figure 1

Extraction of study subject. AF, atrial fibrillation; AFL, atrial flutter; CHA2DS2-VASc, congestive heart failure, hypertension, age of ≥ 75 years [doubled], diabetes mellitus, prior stroke or transient ischemic attack [TIA] [doubled], vascular disease, age of 65 to 74 years, and sex; HIRA-APS, Health Insurance Review & Assessment Service-Aged Population Sample; NOAC, non-vitamin K antagonist oral anticoagulant; NVAF, nonvalvular atrial fibrillation; OAC, oral anticoagulant

Table 1 Demographic characteristics and anticoagulant utilization

Anticoagulants utilization rate

Of the 11,056 patients, 7,238 (65.5%) were receiving OACs on the index date. Among them, 6,302 (87.1%) patients were receiving NOACs. Rivaroxaban was the most commonly prescribed NOAC (32.9%), followed by edoxaban (28.0%), apixaban (26.9%), and dabigatran (12.3%).

Anticoagulant use increased with the increasing age, and anticoagulant use was lower in men than in women. Further, anticoagulant use was higher in patients with congestive heart failure, hypertension, diabetes mellitus, and stroke/TIA, whereas it was lower in patients with vascular disease, anemia, severe renal disease, and prior hemorrhage. The anticoagulant utilization rate was the highest in tertiary hospitals, followed by general hospitals and primary medical institutions/others. Furthermore, it was the highest in the capital city, followed by the six metropolitan cities and other regions. The anticoagulant utilization rate was significantly lower in patients receiving aspirin than in those not receiving aspirin. The anticoagulant utilization rate was the highest for persistent AF, followed by permanent AF, paroxysmal AF, and AFL.

Predictors of anticoagulants utilization

Table 2 presents the results of the multiple logistic regression analysis. Anticoagulant use was higher in patients aged ≥ 75 years than in those aged 65–69 years. Among comorbidities, hypertension was the most influential factor (odds ratio [OR] = 1.644; confidence interval [CI] = 1.445–1.869). Aspirin use had a significantly low OR (OR = 0.097; CI = 0.085–0.110) of anticoagulant use. OAC use was approximately 1.5 times higher in patients with persistent or permanent AF than in those with paroxysmal AF.

Table 2 Adjusted odds ratios and 95% confidence intervals from the multiple logistic regression analysis of anticoagulant utilization


In this study, the anticoagulant underutilization rate was estimated to be 34.5%, which appeared to be better than that reported in previous studies. In a cross-sectional study using National Patients Sample data compiled by the HIRA in 2009, 64.0% of patients with AF and risk factors did not use OAC for one year [16]. In another study using APS data, it decreased annually from 68% in 2011 to 62.5% in 2014 [15]. In a study on the temporal trends of antithrombotic therapy for stroke prevention, OAC prescription showed a constant increase from 32.0% in 2008 to 46.0% in 2015 [17]. Since the method of defining underutilization in each study was different, it is difficult to directly compare the results of these studies, but the overall underutilization rate tended to decrease. However, it is important to note that one-third of the patients with NVAF at high risk of stroke do not receive OAC according to our study. Anticoagulant therapy is suboptimal for patients with AF globally [1, 11], and the anticoagulant therapy rate is relatively lower in patients with NVAF in Asia than in other regions worldwide [19, 20]. The data from GARFIELD-AF (Global Anticoagulant Registry in the FIELD-Atrial Fibrillation) revealed that anticoagulant treatment rate with vitamin K antagonist (VKA) was lower in newly diagnosed NVAF patients in Asia than in other regions (37.8% vs. 53.3%) [19]. GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) also reported that anticoagulant treatment was less in Asia, where 55.2% of NVAF patients received NOAC or VKA between November 2011 and December 2014 compared to patients in Europe (90.1%), or North America (78.3%) [20]. The benefits of anticoagulant therapy in patients with AF have been established regardless of ethnicity [21,22,23,24]; hence, anticoagulant therapy should be administered to all eligible patients.

The diversification of OAC options after the introduction of NOACs has contributed to the reduction in the anticoagulant underutilization rate. By analyzing the type of anticoagulant used, NOACs have surpassed warfarin as an OAC treatment choice. Until 2014, the percentage of NOACs in OACs in AF patients was less than 10% in South Korea [15, 25], but increased significantly to 36.2% in 2015 and 60.8% in 2016 [25]. In another study, NOAC use was estimated to be 10.8% of OAC use in 2013, which increased to 48.3% in 2015 [17]. In our study, it further increased to 87.1%. This result is consistent with the findings of separate studies from other countries. In a study using the Danish nationwide registry, the pattern of initiating OAC treatment was 41% with NOAC in January 2012, but it increased to 76% in December 2015 [26]. Another study using the United Kingdom Clinical Practice Research Datalink showed similar results [27]. In patients with AF and VTE, new VKA use decreased by 31% between 2009 and 2015, while new NOAC use increased by 17-fold between 2012 and 2015, and 56.5% of all OAC prescriptions were NOACs in 2015 [27]. It seems a reasonable change considering that compared to warfarin, NOACs are less susceptible to interactions with food or other drugs and have the advantage of not requiring regular blood tests. In our study, the most used NOAC was rivaroxaban, consistent with that reported in a previous study in 2015 [17]. While the UK study showed the same trend as our study in 2015, apixaban was the most preferred NOAC in Denmark in the same year [26, 27].

When comparing the risk factors for anticoagulant underutilization with those of previous studies, it is remarkable that women no longer have higher underutilization rates than men [15,16,17]. This is in line with the findings from previous studies, in which the transition from warfarin to NOAC was faster in women [28]. It is presumed that women were less satisfied with warfarin therapy, and the improvement in treatment rate after the introduction of new drugs was more prominent in female patients than in male patients [28].

Anemia, severe renal disease, and prior hemorrhage are comorbidities that significantly increase the bleeding risk as a component of the ATRIA (anticoagulation and risk factors in AF) bleeding score along with age (> 75 years) and hypertension. Although current guidelines recommend that a high bleeding risk score cannot be a contraindication to anticoagulant therapy [7,8,9, 29], OAC is still avoided in these patients. Moreover, NOAC has reduced the bleeding risk in Asians [30, 31], and it is presumed that the fear of bleeding still has a significant effect on OAC utilization. Recognizing that the benefits outweigh the risks of anticoagulation even in patients with a high bleeding risk is important for appropriate anticoagulant therapy. Aspirin use is one of the most significant risk factors of anticoagulant underutilization. OAC underutilization for AF may be perpetuated by aspirin use, which remains a soft option for physicians based on a misunderstanding of the safety and efficacy of aspirin [32]. GLORIA-AF revealed that aspirin use was inversely associated with anticoagulant utilization [20]. Several studies have demonstrated that aspirin has no benefit for stroke prevention in patients with AF and increases the risk of bleeding [33,34,35]. Hence, aspirin has been excluded from the treatment options in recent guidelines [7, 9, 36, 37], but these changes have not been fully integrated in clinical practice. Aspirin should no longer be recognized as a soft option, and it is necessary to further encourage physicians to select a better antithrombotic option.

Based on the level of healthcare facilities, OAC use was the highest in tertiary hospitals, followed by general hospitals and primary medical institutions/others. This is consistent with the order of more active use of new treatments, which has been shown consistently in other studies [38]. Regarding AF types, the OAC utilization rate was significantly higher in patients with persistent and permanent AF than in those with paroxysmal AF and AFL. This seems to be related to the degree of stroke risk [39,40,41]. However, AF guidelines recommend OAC therapy for stroke prevention regardless of the AF type [7,8,9,10] since significant episodes of stroke occur even in patients with paroxysmal AF [42]. There was no significant difference depending on the region.

This study has some limitations. First, we used claims data, which were collected with the purpose of reimbursement and not for clinical or research purposes; therefore, information on diagnosis may be susceptible to upcoding by providers looking for a higher reimbursement rate [43]. Moreover, since the data did not include uninsured events, we could not obtain some information, such as over-the-counter aspirin use. Second, these claims data did not contain clinical data such as laboratory test results, disease severity, or patient-reported outcomes [44]. Therefore, we estimated the clinical status of patients using the provided disease codes (“Appendix”). Third, socioeconomic factors such as income, education, and health behaviors were not reflected. Finally, AF types are difficult to distinguish clearly, and the proportion classified as others is quite high (31.9%); therefore, the effect of AF type on OAC use may not be accurate.

Despite these limitations, this study is meaningful. It reports the use of anticoagulants in the recent time when OAC choices have become diverse and NOACs are widely used. In addition, in this study, we defined only those who were taking medication as of July 1, 2018, as OAC users for obtaining data closer to the actual use, unlike previous studies that used the conservative method of defining OAC users if OAC was used even once a year.


This study demonstrates that approximately one-third of patients who are recommended anticoagulation therapy do not take OAC, even though using NOACs has become more common. It should be widely recognized that aspirin cannot be an alternative to OAC, and anticoagulant therapy should be actively implemented.


  1. Benjamin EJ, Muntner P, Alonso A, et al. Heart disease and stroke statistics-2019 update: a report from the American heart association. Circulation. 2019;139(10):e56–528.

    Article  Google Scholar 

  2. Zulkifly H, Lip GYH, Lane DA. Epidemiology of atrial fibrillation. Int J Clin Pract. 2018;72(3):e13070.

    Article  Google Scholar 

  3. Colilla S, Crow A, Petkun W, et al. Estimates of current and future incidence and prevalence of atrial fibrillation in the US adult population. Am J Cardiol. 2013;112(8):1142–7.

    Article  Google Scholar 

  4. Kim D, Yang PS, Jang E, et al. 10-year nationwide trends of the incidence, prevalence, and adverse outcomes of non-valvular atrial fibrillation nationwide health insurance data covering the entire Korean population. Am Heart J. 2018;202:20–6.

    Article  Google Scholar 

  5. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham study. Stroke. 1991;22(8):983–8.

    Article  CAS  Google Scholar 

  6. Lin HJ, Wolf PA, Kelly-Hayes M, et al. Stroke severity in atrial fibrillation. The Framingham study. Stroke. 1996;27(10):1760–4.

    Article  CAS  Google Scholar 

  7. January CT, Wann LS, Calkins H, et al. 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. Heart Rhythm. 2019.

  8. Lip GYH, Banerjee A, Boriani G, et al. Antithrombotic therapy for atrial fibrillation: CHEST guideline and expert panel report. Chest. 2018;154(5):1121–201.

    Article  Google Scholar 

  9. Lee JM, Joung B, Cha MJ, et al. Erratum: 2018 KHRS guidelines for stroke prevention therapy in korean patients with nonvalvular atrial fibrillation. Korean J Med. 2018;93(3):311–2.

    Article  Google Scholar 

  10. Brieger D, Amerena J, Attia JR, et al. National heart foundation of Australia and Cardiac Society of Australia and New Zealand: Australian clinical guidelines for the diagnosis and management of atrial fibrillation 2018. Med J Aust. 2018;27:1209–66.

    Google Scholar 

  11. Gamra H, Murin J, Chiang CE, et al. Use of antithrombotics in atrial fibrillation in Africa, Europe, Asia and South America: insights from the International RealiseAF Survey. Arch Cardiovasc Dis. 2014;107(2):77–87.

    Article  Google Scholar 

  12. Ogilvie IM, Newton N, Welner SA, et al. Underuse of oral anticoagulants in atrial fibrillation: a systematic review. Am J Med. 2010;123(7):638-645.e634.

    Article  CAS  Google Scholar 

  13. Bai Y, Wang YL, Shantsila A, et al. The global burden of atrial fibrillation and stroke: a systematic review of the clinical epidemiology of atrial fibrillation in Asia. Chest. 2017;152(4):810–20.

    Article  Google Scholar 

  14. Liu T, Yang H-l, Gu L, et al. Current status and factors influencing oral anticoagulant therapy among patients with non-valvular atrial fibrillation in Jiangsu province, China: a multi-center, cross-sectional study. BMC Cardiovasc Disord. 2020;20(1):22.

    Article  CAS  Google Scholar 

  15. Choi EJ, Lee IH, Je NK. Inadequate stroke prevention in Korean atrial fibrillation patients in the post-warfarin era. Int J Cardiol. 2016;220:647–52.

    Article  Google Scholar 

  16. Lee IH, Kim H, Je NK. Underutilization of warfarin for stroke prophylaxis in patients with atrial fibrillation or atrial flutter in Korea. J Cardiol. 2015;66(6):475–81.

    Article  Google Scholar 

  17. Lee SR, Choi EK, Han KD, et al. Temporal trends of antithrombotic therapy for stroke prevention in Korean patients with non-valvular atrial fibrillation in the era of non-vitamin K antagonist oral anticoagulants: a nationwide population-based study. PLoS ONE. 2017;12(12):e0189495.

    Article  Google Scholar 

  18. Service NHI. National Health Insurance System of Korea. wwwkobiakr/skin/bbs/downloads_e2/downloadphp?tbl=policy_report&no=401. 2015.

  19. Oh S, Goto S, Accetta G, et al. Vitamin K antagonist control in patients with atrial fibrillation in Asia compared with other regions of the world: Real-world data from the GARFIELD-AF registry. Int J Cardiol. 2016;223:543–7.

    Article  Google Scholar 

  20. Huisman MV, Rothman KJ, Paquette M, et al. The changing landscape for stroke prevention in AF: findings from the GLORIA-AF registry phase 2. J Am Coll Cardiol. 2017;69(7):777–85.

    Article  Google Scholar 

  21. Xian Y, O’Brien EC, Liang L, et al. Association of preceding antithrombotic treatment with acute ischemic stroke severity and in-hospital outcomes among patients with atrial fibrillation. JAMA. 2017;317(10):1057–67.

    Article  Google Scholar 

  22. Chan YH, See LC, Tu HT, et al. Efficacy and safety of apixaban, dabigatran, rivaroxaban, and warfarin in Asians with nonvalvular atrial fibrillation. J Am Heart Assoc. 2018;7(8).

  23. 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(10):2819–28.

    Article  CAS  Google Scholar 

  24. Hankey GJ, Stevens SR, Piccini JP, et al. Intracranial hemorrhage among patients with atrial fibrillation anticoagulated with warfarin or rivaroxaban: the rivaroxaban once daily, oral, direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation. Stroke. 2014;45(5):1304–12.

    Article  CAS  Google Scholar 

  25. Ko YJ, Kim S, Park K, et al. Impact of the health insurance coverage policy on oral anticoagulant prescription among patients with atrial fibrillation in Korea from 2014 to 2016. J Korean Med Sci. 2018;33(23):e163.

    Article  Google Scholar 

  26. Staerk L, Fosbøl EL, Gadsbøll K, et al. Non-vitamin K antagonist oral anticoagulation usage according to age among patients with atrial fibrillation: temporal trends 2011–2015 in Denmark. Sci Rep. 2016;6:31477.

    Article  CAS  Google Scholar 

  27. Loo SY, Dell’Aniello S, Huiart L, et al. Trends in the prescription of novel oral anticoagulants in UK primary care. Br J Clin Pharmacol. 2017;83(9):2096–106.

    Article  CAS  Google Scholar 

  28. Park S, Je NK. Factors that affect time to switch from warfarin to a direct oral anticoagulant after change in the reimbursement criteria in patients with atrial fibrillation. J Cardiovasc Pharmacol Ther. 2020;25(1):57–64.

    Article  Google Scholar 

  29. Steffel J, Verhamme P, Potpara TS, 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(16):1330–93.

    Article  CAS  Google Scholar 

  30. Cha MJ, Choi EK, Han KD, et al. Effectiveness and safety of non-vitamin K antagonist oral anticoagulants in Asian patients with atrial fibrillation. Stroke. 2017;48(11):3040–8.

    Article  CAS  Google Scholar 

  31. Yasaka M, Lip GY. Impact of non-vitamin k antagonist oral anticoagulants on intracranial bleeding in Asian patients with non-valvular atrial fibrillation. Circ J. 2014;78(10):2367–72.

    Article  CAS  Google Scholar 

  32. Ben Freedman S, Gersh BJ, Lip GY. Misperceptions of aspirin efficacy and safety may perpetuate anticoagulant underutilization in atrial fibrillation. Eur Heart J. 2015;36(11):653–6.

    Article  CAS  Google Scholar 

  33. Olesen JB, Lip GY, Lindhardsen J, et al. Risks of thromboembolism and bleeding with thromboprophylaxis in patients with atrial fibrillation: a net clinical benefit analysis using a “real world” nationwide cohort study. Thromb Haemost. 2011;106(4):739–49.

    CAS  PubMed  Google Scholar 

  34. Ogilvie IM, Welner SA, Cowell W, et al. Ischaemic stroke and bleeding rates in “real-world” atrial fibrillation patients. Thromb Haemost. 2011;106(1):34–44.

    Article  CAS  Google Scholar 

  35. Lip GY. The role of aspirin for stroke prevention in atrial fibrillation. Nat Rev Cardiol. 2011;8(10):602–6.

    Article  CAS  Google Scholar 

  36. National Clinical Guideline C. National Institute for Health and Clinical Excellence: Guidance. In: Atrial Fibrillation: The Management of Atrial Fibrillation. London: National Institute for Health and Care Excellence (UK) Copyright © National Clinical Guideline Centre, 2014;2014.

  37. Camm AJ, Lip GY, De Caterina R, et al. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association. Eur Heart J. 2012;33(21):2719–47.

    Article  Google Scholar 

  38. Kim J, Park S, Kim H, et al. National trends in metformin-based combination therapy of oral hypoglycaemic agents for type 2 diabetes mellitus. Eur J Clin Pharmacol. 2019;75(12):1723–30.

    Article  CAS  Google Scholar 

  39. Vanassche T, Lauw MN, Eikelboom JW, et al. Risk of ischaemic stroke according to pattern of atrial fibrillation: analysis of 6563 aspirin-treated patients in ACTIVE-A and AVERROES. Eur Heart J. 2014;36(5):281–8.

    Article  Google Scholar 

  40. Al-Kawaz M, Omran SS, Parikh NS, et al. Comparative risks of ischemic stroke in atrial flutter versus atrial fibrillation. J Stroke Cerebrovasc Dis. 2018;27(4):839–44.

    Article  Google Scholar 

  41. Link MS, Giugliano RP, Ruff CT, et al. Stroke and mortality risk in patients with various patterns of atrial fibrillation: results from the ENGAGE AF-TIMI 48 trial (effective anticoagulation with factor Xa next generation in atrial fibrillation-thrombolysis in myocardial infarction 48). Circ Arrhythm Electrophysiol. 2017;10(1).

  42. Wang Y, Ma C-S, Du X, et al. Thromboembolic risks associated with paroxysmal and persistent atrial fibrillation in Asian patients: a report from the Chinese atrial fibrillation registry. BMC Cardiovasc Disord. 2019;19(1):283.

    Article  Google Scholar 

  43. Kim L, Kim J-A, Kim S. A guide for the utilization of health insurance review and assessment service national patient samples. Epidemiol Health. 2014;36:e2014008.

    Article  Google Scholar 

  44. Kim S, Kim M-S, You S-H, et al. Conducting and reporting a clinical research using korean healthcare claims database. Korean J Fam Med. 2020;41(3):146–52.

    Article  Google Scholar 

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We used Aged Population Sample data from 2018 that were collected by the Korea Health Insurance Review and Assessment Service (HIRA-APS-2018-0039); however, the results are not related to the Ministry of Health and Welfare or HIRA.

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Correspondence to Nam Kyung Je.

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Appendix: Disease and medication codes

Appendix: Disease and medication codes


Atrial fibrillation

I48, I480–I484, I489

Paroxysmal atrial fibrillation


Persistent atrial fibrillation


Permanent atrial fibrillation


Atrial flutter


Atrial fibrillation and atrial flutter

I48, I489

Congestive heart failure

I50, I110, I130, I132



Diabetes mellitus


Prior stroke or transient ischemic attack or thromboembolism

G45, I26, I63-64, I676, I74, I80, I82

Vascular disease

I21–24, I70, I73


D50–53, D55, D59–64

Severe renal disease

N184-185, T824, Y841, Z49, Z940, Z992

Renal disease

I12–13, N03–05, N10–12, N14–19, Z940, N184–185, T824, Y841, Z49, Z992

Previous hemorrhage

I60–62, I690–692, K2211, K226, K250, K252, K254, K256, K260, K262, K264, K266, K270, K272, K274, K276, K280, K282, K284, K286, K290, K625, K920–922

Valvular heart disease

I050, I052, I059, I080–081, I083, I089, I342, I349, T820, T826, Z952–954



613701AC, 613702AC


511401AT, 511402AT, 511403AT, 511404AT


617001AT, 617002AT


643601AT, 643602AT, 643603AT


249103AT, 249105AT


110701AT, 110702AT, 110801AT, 110802AT, 111001AC, 111001AT, 111002AT, 111003AC, 111003AT, 517900AC, 517900AT, 667500AC, 489700AC

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Park, S., Je, N.K. Underutilization of anticoagulants in patients with nonvalvular atrial fibrillation in the era of non-vitamin K antagonist oral anticoagulants. Int J Arrhythm 23, 1 (2022).

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