br Material and methods br
Material and methods
Results A total of 4014 subjects were enrolled and registered during the initial recruitment flap inhibitor from September 2013 through March 2015. In total, 167 subjects were excluded because of missing pivotal data such as height, body weight, or age (date of birth). Finally, 3847 subjects were analyzed for baseline characteristics as shown in Table 1. The mean CHADS2 score was 1.81±1.27, the mean CHADS2-Vasc score was 3.02±1.58, and the mean HAS-BLED score was 2.23±1.06. The usage rate of warfarin was 44.2% overall, and the usage rate of NOACs was 33.5%.
Discussion In earlier years, studies comparing antiplatelet agents such as aspirin salicylate and thienopyridine derivatives with vitamin K-dependent oral anticoagulants and coumarin derivatives such as warfarin were performed to evaluate the efficacy and safety of these drugs for the prevention of thrombotic diseases in subjects with AF [21,22]. Warfarin use with dosage adjustments by prothrombin time-international normalized ratio monitoring strategies was shown to be significantly more effective compared to antiplatelet agents by various clinical trials so far [23–25]. However, although warfarin effectively prevents the development of thrombotic diseases in patients with AF [26,27], the inherent laborious and complex dosage adjustments seemed to cause a low utilization rate of warfarin in relatively lower doses in various clinical observational trials performed in Japan, including the Fushimi AF Registry by Akao et al. [28–30]. In the Fushimi AF Registry, warfarin-based anticoagulant therapies were not widely used in actual clinical settings, with a utilization rate of only 48.5%. In our current analyses, the utilization rate of warfarin was about 44.2%, but the total utilization rate of anticoagulants increased to 77.7% (Table 1). The drugs prescribed to the remaining subjects were antiplatelet agents, such as acetylsalicylic acid, or no drug was prescribed to prevent thrombotic diseases, reflecting the so-called “underuse” of anticoagulants seen in the Fushimi AF Registry. In addition, potential pharmacological dilemmas have led to risk/benefit conflicts. Inappropriate use of warfarin has sometimes resulted in unexpected hemorrhagic events, such as cerebral hemorrhage and gastrointestinal hemorrhage, which can be lethal. As compared with Caucasians, various clinical trials have shown that Asians have a higher risk of cerebral hemorrhage; patients receiving warfarin or other anticoagulants must therefore be closely monitored [31–34]. Other factors such as numerous drug/drug and drug/food interactions and an increased risk of excessive bleeding [35,36] have also discouraged the use of warfarin in Asia. In particular, Asians have a 4-fold higher risk of warfarin-induced intracranial hemorrhage as well as major gastrointestinal bleeding compared to non-Asians [33,37]. These factors have also had a negative impact on the effective use of warfarin, contributing to substantial underutilization . To resolve such “unmet” needs in actual clinical settings, NOACs, such as dabigatran, apixaban, rivaroxaban, and edoxaban, were recently developed and successively launched in Japan. Finally, we have entered the era of NOACs for the management of AF. To date, multiple phase III clinical trials and subsequent post-hoc analyses assessing the efficacy and the safety of NOACs have shown either non-inferiority or superiority to warfarin treatment [17–20]. The efficacy and the safety of dose adjustments in accordance with the individual characteristics of patients, including factors such as post-ischemic stroke [39,40], advanced age [41,42], and concurrent renal impairment [43,44], have been examined under various clinical conditions. Owing to racial differences from patients enrolled in international clinical trials, Japanese clinical trials have consistently shown Lytic infection NOACs are effective and safe in Japanese patients [33,45–49]. In Japan, NOACs as well as warfarin can be used under national coverage by the public health-care insurance system, placing a lower financial burden on patients than that in other countries. Because clinical trials are generally performed in artificially controlled circumstances, the safety and efficacy demonstrated by such studies is generally limited. Unexpected complications and adverse effects or unknown clinical issues that are newly identified should be tested and clarified in actual clinical settings. ASSAF-K is characterized by the participation of medical practitioners in Kanagawa, Japan, which is a representative urban area in a modern developed country. ASSAF-K is expected to reveal the current status of the treatment and outcomes of patients with AF, including rates of compliance with clinical guidelines, and to provide proof of the correctness or inadequacy of current guideline-based treatments for AF in Japan.