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 . In another study using APS data, it decreased annually from 68% in 2011 to 62.5% in 2014 . 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 . 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%) . 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%) . 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 . In another study, NOAC use was estimated to be 10.8% of OAC use in 2013, which increased to 48.3% in 2015 . 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 . Another study using the United Kingdom Clinical Practice Research Datalink showed similar results . 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 . 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 . 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 . 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 .
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 . GLORIA-AF revealed that aspirin use was inversely associated with anticoagulant utilization . 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 . 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 . 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 . 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 . 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.