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  • NS-398 Since antithrombotic therapy for patients with AF

    2019-04-15

    Since antithrombotic therapy for patients with AF is rapidly changing with the increasing use of dabigatran, rivaroxaban, and apixaban, some of the primary issues that will influence the future revision of various guidelines (HRS [Heart Rhythm Society], ESC [European Society of Cardiology], ACC [American College of Cardiology], CCS [Canadian Cardiovascular Society], JCS [Japanese Circulation Society], etc.) would be how to use warfarin and other drugs for different indications and to determine the most accurate clinical position of each drug. In particular, there are data currently suggesting that the bleeding risk associated with newer anticoagulants is lower than that of warfarin [11–14]. Therefore, a central point in the new guidelines or statements would be to expand the indications of these newer anticoagulant drugs to include low-risk patients (CHADS2 score 0/1) and to reconsider the indications of antiplatelet agents, including acetylsalicylic NS-398 (ASA).
    Current status of international guidelines after launch of novel anticoagulants When developing guidelines on antithrombotic therapy, we must consider that novel anticoagulants are approved in different countries at different times. Since the primary role of guidelines is to describe how to use currently available drugs, guidelines used in a country should describe regimens of drugs currently available in that country. However, the approval status of dabigatran, rivaroxaban, apixaban, and edoxaban as of the end of 2012 differs among Asia-Pacific countries (Table 1), and this may pose a problem in establishing a common guideline document for those countries. Table 2 lists current guidelines for antithrombotic therapy in AF. The Joint Working Groups for the Guidelines for Pharmacotherapy of Atrial Fibrillation (JCS 2008, referred to as the “JCS 2008” guidelines hereinafter) [9] published an urgent statement on antithrombotic therapy of AF in 2011 after the launch of dabigatran in Japan [15]. The ESC 2010 guidelines for the management of AF (referred to as the “ESC 2010” guidelines) [4] recommend risk stratification according to the CHADS2 score, and recommend the CHA2DS2-VASc score in low-risk patients with a CHADS2 score of 0/1. Although all relevant guidelines describe that oral anticoagulants (OACs) are indicated for patients with a CHADS2 score of ≥2, the indication differs across guidelines. The ESC 2010 guidelines describe that dabigatran may be considered an alternative to warfarin; the “Quick Reference Guide: Atrial Fibrillation Information for the Health Practitioner” proposed by the government of Western Australia (referred to as the “Australian 2011” guidelines) [6] lists warfarin only; the evidence-based clinical practice guidelines for antithrombotic therapy for AF proposed by the American College of Chest Physicians (referred to as the “ACCP 2012” guidelines) [3] made recommendations only for dabigatran, which was approved for use in AF, among novel OACs as an alternative to warfarin; and the focused 2012 update of the CCS AF guidelines (referred to as the “CCS 2012” guidelines) [8] suggest that when OAC therapy is indicated, most patients should receive dabigatran, rivaroxaban, or apixaban in preference to warfarin, since all these drugs are associated with less intracranial hemorrhage (ICH) and are much simpler to use. However, the CCS 2012 guidelines describe that the preference for one of the novel OACs over warfarin is less marked among patients already receiving warfarin with stable international normalized ratio (INR) and no bleeding complications. The ESC 2012 focused update guidelines [5] use a description of novel OACs to include apixaban, which was not approved yet at the time of revision. It should be emphasized, however, that in the ROCKET AF [13] (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) trial, patients with a CHADS2 score of ≥2 were investigated and thus rivaroxaban should be indicated for this population of patients. The JCS\'s urgent statement [15] recommends that factor Xa inhibitors currently under development will be included as drugs “recommended” or “can be considered” for use according to the CHADS2 score of patients evaluated in clinical trials. On the basis of this consideration, the JCS\'s urgent statement placed dabigatran as a drug of choice for patients with a CHADS2 score of 1 and warfarin as a drug that “can be considered.”