What’s the “go to” anticoagulant for stroke prevention in atrial fibrillation?

Novel oral anticoagulants promise myriad advantages over warfarin for stroke prevention in atrial fibrillation (AF). In global megatrials undertaken to compare efficacy and safety with warfarin, these new drugs appear to have a net clinical benefit with fewer strokes and fewer head bleeds. Dabigatran and rivaroxaban have received licenses for stroke prevention in AF, and apixaban’s approval is expected soon. Additional drugs such as edoxaban are making rapid headway in the pipeline. The question for the individual practitioner is whether to change personal clinical practice. Warfarin has been marketed since 1954. It is difficult to dose properly and has hundreds of drug-drug and drugfood interactions which make achieving the target therapeutic range with an International Normalised Ratio (INR) between 2.0 and 3.0 more than a bit challenging. Excellence in warfarin dosing is usually measured by the yardstick of a time within the therapeutic range (TTR) of 60% or greater. Yet, under almost no other circumstances in life is a 60% success rate considered excellent. Anticoagulation experts themselves proffer divided opinions and uncertainty. Front-line practitioners realise that there is a glut of information, without a unifying and reliable educational source to which they can turn for advice. Separate practice guidelines are issued by the American Heart Association/American College of Cardiology/ Heart Rhythm Society (1), European Society of Cardiology (2), and American College of Chest Physicians (3). Important differences exist among these three sets of guidelines (4). There are substantial and clinically important differences among 12 published schemes to stratify stroke risk in AF (5). And there is confusion about which is the optimal scoring tool for bleeding risk assessment: HAS-BLED (6), ATRIA (7), or HEMORR2HAGES (8). Furthermore, uncertainty abounds among practitioners about how to balance thromboembolic stroke risk with bleeding risk. Nevertheless, valiant attempts are being made to achieve consensus on a set of best practices (9). Uncertainty for the practitioner is encapsulated in a “Controversies in Cardiovascular Medicine” debate published in Circulation. Jack Ansell, MD takes the position that new oral anticoagulants should not be used as first-line agents to prevent stroke in patients with AF (10). He enumerates his personal assessment of the principal disadvantages of novel oral anticoagulants as follows: 1) The short half-life (does not protect against stroke in patients with poor drug adherence); 2) Lack of routine coagulation monitoring (may lower patient adherence); 3) Routine measurement of the precise anticoagulation effect is not available (but might be important to understand why certain patients suffer stroke or major bleeding); 4) Inability to titrate dose; 5) No antidote, and 6) High drug cost. Christopher B. Granger, MD argues that novel oral anticoagulants should be used as first-line agents to prevent stroke in patients with AF (11). He cites the lower stroke rate, lower bleeding rate, lower mortality rate, and markedly improved convenience of the novel oral anticoagulants compared with warfarin in rigorously executed large randomised controlled trials. With regard to Ansell’s concern about low patient adherence to novel oral anticoagulants, Granger reminds us that in the AVERROES Trial of apixaban versus aspirin (12), adherence to apixaban was better than adherence to aspirin. The debate about using warfarin or novel oral anticoagulants as first line agents ignores a fundamental problem in the quest to prevent stroke in AF. Physicians are by nature conservative. They remain reluctant to prescribe warfarin to AF patients at greatest risk of stroke – those who are elderly. Front-line practitioners fear the risk of bleeding from falls and get scared when a patient reports any history of prior bleeding (13). In many instances, physicians, nurse practitioners, and physicians’ assistants remain uncertain whether to prescribe any anticoagulant whatsoever. To inform patients about the risks of stroke in AF and the benefits of anticoagulants to prevent stroke, the American College of Physicians Foundation (www.acpfoundation.org) has just released a series of educational tools for patients and clinicians. These enduring materials have easy to read information for the public and onepage worksheets to facilitate clinicians’ assessment of when the benefit of anticoagulation outweighs the risk in patients with atrial fibrillation. The availability of this practical and relevant information is an important step forward. In the current issue of Thrombosis and Haemostasis, Banerjee et al. take a unique approach toward dissecting the facts surrounding warfarin and novel oral anticoagulants and comparing them with no anticoagulant treatment in a Danish cohort from the Danish National Patient Registry (14). Based on available information from