Stroke 2006; van Walraven C, Hart RG, Singer DE, et al. Dabigatran etexilate for stroke prevention in patients with atrial fibrillation: Resolving uncertainties in routine practice. Comparative validation of a novel risk score for predicting bleeding risk in anticoagulated patients with atrial fibrillation: the HASBLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly) score. Men are more commonly affected than women and the prevalence increases with age. Both atrial fibrillation and chronic kidney disease are associated with increased risk of stroke and thromboembolic complications. AF is a growing clinical problem owing to the ageing population, and the advances in treatment and improved survival of patients with cardiac disorders such as ischaemic heart disease and heart failure, which predispose to AF.4 It is estimated that, by 2050, up to 16 million people in the US will suffer from AF,5 which is already the commonest arrhythmia encountered in clinical practice.6 The healthcare costs are substantial and AF accounts for 1 % of the National Health Service expenditure in the UK.7. A Phase IV study is investigating various reversal strategies for dabigatran,49 and there is interest around an antibody against the fragment antigen-binding (FAB fragment) of dabigatran being used as a potential antidote: this may work in a similar manner to antibodies used against digoxin in cases of digoxin toxicity. Objectives: The purpose of this study was to describe patterns of OAC use in ESRD patients with AF and their associations with cardiovascular outcomes. Atrial fibrillation: Anticoagulants Discuss the risks and benefits of anticoagulation so that the person can make an informed choice about their treatment. The CHA2DS2-VASc score18 has been proposed and, in various independent validation cohorts, has been shown to reliably identify ‘truly low-risk’ patients (annual stroke rate <1 % per year) and classes fewer patients as ‘intermediate-risk’.19 It also seems to be at least as good as – or possibly better than – the CHADS2 score at identifying ‘high-risk’ patients.19 This score has now been included in international guidelines.20. Hypertension is defined as a systolic blood pressure >160 mmHg. Vitamin K antagonism has been the mainstay of treatment; however, newer drugs with novel mechanisms are also available. The copyright in this work belongs to Radcliffe Medical Media. A consensus document of the Italian Federation of Thrombosis Centers (FCSA). Discontinuation rates were 21 % in the dabigatran 110 mg group, 21 % in the dabigatran 150 mg group and 17 % in the warfarin group at the end of the second year (p<0.001 for dabigatran versus warfarin). Apixaban: an emerging oral factor Xa inhibitor. This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. Dabigatran is the only drug to significantly reduce the risk of ischaemic stroke. Use of anticoagulation in elderly patients with atrial fibrillation who are at risk for falls. technical support for your product directly (links go to external sites): Thank you for your interest in spreading the word about The BMJ. However, to ensure that the benefits exceed the risks of bleeding, appropriate patient selection is essential. Oral anticoagulation in patients with atrial fibrillation: adherence with guidelines in an elderly cohort. Gregory YH Lip has served as a consultant for Bayer, Astellas, Merck, Astr aZeneca, Sanofi, BMS/Pfizer, Daiichi-Sankyo, Biotronik, Portola and Boehringer Ingelheim; he has been on the speakers bureau for Bayer, BMS/Pfizer, Boehring er Ingelheim and Sanofi Aventis. Questions and answers on the use of dabigatran and perpectives on the use of other new oral anticoagulants in patients with atrial fibrillation. There are several important considerations when selecting anticoagulant therapy for patients with atrial fibrillation. It can periodically be reassessed and has been validated in various large real-world cohorts,23 performing favourably compared with other bleeding risk scores.24 The HAS-BLED score has been incorporated into international guidelines. These novel oral anticoagulants (direct thrombin inhibitors and factor Xa inhibitors) obviate many of warfarin’s shortcomings, and they have demonstrated safety and efficacy in large randomized trials of patients with non-valvular atrial fibrillation. Effect of study setting on anticoagulation control: A systematic review and metaregression. One of the major goals in treating AF is a reduction in the incidence of thromboembolic stroke, the most feared complication of AF. Many of the risk factors for stroke are also risk factors for bleeding and, at higher HAS-BLED scores, the net clinical benefit of warfarin is actually greater. White RH, McBurnie MA, Manolio T, et al. Treatments for atrial fibrillation include medicines to control heart rate and reduce the risk of stroke, and procedures such as cardioversion to restore normal heart rhythm. Steger C, Pratter A, Martinek-Bregel M, et al. Olesen JB, Lip GY, Lindhardsen J, et al. Despite the proven efficacy of warfarin, a string of limitations have meant that it is underused by physicians and patients alike. When managing a haemorrhage associated with the use of warfarin, or in other scenarios when prompt reversal of anticoagulation is necessary, there is an established antidote in the form of vitamin K. There are no known antidotes currently available in clinical practice for dabigatran, rivaroxaban or apixaban. Beasley BN, Unger EF, Temple R. Anticoagulant options – why the FDA approved a higher but not a lower dose of dabigatran. Underuse of oral anticoagulants in atrial fibrillation: a systematic review. Pengo V, Crippa L, Falanga A, et al. Where views/opinions are Wolf PA, Abbott RD, Kannel WB. Lip GY, Frison L, Halperin JL, Lane DA. Stroke and thromboembolism in atrial fibrillation: a systematic review of stroke risk factors, risk stratification schema and cost effectiveness data. expressed, they are those of the author(s) and not of Radcliffe Medical For more than 50 years, warfarin has been the primary medication used to reduce the risk of thromboembolic events in patients with atrial fibrillation. New drugs should circumvent many of the limitations associated with warfarin that necessitate regular coagulation monitoring. Both authors approve the final version of the manuscript and are guarantors. Guidelines for managing atrial fibrillation recommend systemic anticoagulation for almost all patients age 65 and older, but in practice up to 50% of older patients do not receive maintenance anticoagulation therapy. The primary efficacy outcomes were stroke or systemic embolism. Hylek EM, D’Antonio J, Evans-Molina C, et al. Ischaemic stroke associated with AF is nearly twice as likely to be fatal as non-AF str… Risks of thromboembolism and bleeding with thromboprophylaxis in patients with atrial fibrillation: A net clinical benefit analysis using a 'real world' nationwide cohort study. Hughes M, Lip GY. Steinberg BA, Peterson ED, Kim S, et al. Background: It is uncertain whether bridging anticoagulation is necessary for patients with atrial fibrillation who need an interruption in warfarin treatment for an elective operation or other elective invasive procedure. Does warfarin for stroke thromboprophylaxis protect against MI in atrial fibrillation patients? Watson T, Shantsila E, Lip GY. Anticoagulation therapy in patients with atrial fibrillation is important. Patients with atrial fibrillation (AF) are at increased thromboembolic risk, and they suffer more severe strokes with worse outcomes. Lakshminarayan K, Solid CA, Collins AJ, et al. The arrhythmia is associated with significant morbidity and mortality, mainly due to thromboembolic events including stroke and systemic embolisms. Cost of an emerging epidemic: an economic analysis of atrial fibrillation in the UK. The use of oral anticoagulation in patients with atrial fibrillation at moderate or high risk of stroke, estimated by established criteria, improves outcomes. Bleeding is the most feared complication of antithrombotic therapy, and this can limit the prescription of oral anticoagulants.21 The HAS-BLED score22 is a simple tool to aid clinicians in undertaking a bleeding risk assessment and prompts them to consider the correctable risk factors for bleeding, such as labile international normalized ratios (INRs), uncontrolled hypertension and concomitant drugs. Crossref Medline Google Scholar; 30. Hypertension is defined as blood pressure consistently above 140/90 mmHg or treated hypertension on medication. Bleeding risk in ‘real world’ patients with atrial fibrillation: comparison of two established bleeding prediction schemes in a nationwide cohort. While it is always difficult to infer comparisons between drugs that have not been tested against each other, there are some differences in the evidence, which clinicians may use to help determine the optimal antithrombotic strategy. Anticoagulants in atrial fibrillation. The role of aspirin for stroke prevention in atrial fibrillation. Pharmacokinetic & Pharmacodynamic Properties of Novel Anticoagulants, Potential Limitations of Novel Anticoagulants. Radcliffe Cardiology is part of Radcliffe Medical Media, an independent Antithrombotic therapy to prevent stroke in patients with atrial fibrillation: A meta-analysis. Alternatives to warfarin must be proven to reliably perform at least as well as warfarin in RCTs, with an acceptable safety profile (ximelegatran was withdrawn due to hepatotoxicity36). Lip GY, Edwards SJ. In 2006, the ACTIVE-W (Atrial fibrillation clopidogrel trial with irbesartan for prevention of vascular events) compared dual antiplatelet therapy with aspirin and clopidogrel to warfarin for the prevention of thromboembolism in AF.37 The trial was stopped early due to the clear superiority of warfarin over dual antiplatelet therapy. Dabigatran has the propensity to cause dyspepsia and gastrointestinal haemorrhage (likely caused by its acidic core), which may limit its use in patients with gastrointestinal upset. This lesson is all about anticoagulation in atrial fibrillation. Please note: your email address is provided to the journal, which may use this information for marketing purposes. This review consists of three parts: chronic anticoagulation, anticoagulation for cardioversion, and a brief comment on anticoagulation around the time of left atrial radiofrequency ablation. Apixaban is an oral, selective and reversible direct factor Xa inhibitor.45 The ARISTOTLE (Apixaban for the prevention of stroke in subjects with atrial fibrillation) study was a randomised, Phase III, double-blind trial comparing apixaban 5 mg twice daily with warfarin titrated to an INR between 2 and 3 in over 18,000 patients.46 The primary outcome was stroke (either ischaemic or haemorrhagic) or systemic embolism, which occurred at a rate of 1.27 % per year in the apixaban group versus 1.60 % per year in the warfarin group (HR 0.79, 95 % CI 0.66–0.95, p<0.001 for non-inferiority, p=0.01 for superiority). Furthermore, the rates of bleeding in the two groups were very similar (2.4 % per year for clopidogrel and aspirin versus 2.2 % per year for warfarin). Deciding when to initiate oral anticoagulation in patients with non-valvular atrial fibrillation is a longstanding, common, and unresolved clinical challenge. Anticoagulation control and prediction of adverse events in patients with atrial fibrillation: a systematic review. Midland Research Practices Network (MidReC): Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial. Atrial fibrillation: an old disease, a new epidemic. Anticoagulation for Stroke Prevention in Patients With Atrial Fibrillation and End-Stage Renal Disease—First, Do No Harm Emilie P. Belley-Cote, MD, PhD 1,2 ; John W. Eikelboom, MBBS, MSc 1,2 Author Affiliations Article Information To recognise and overcome barriers to anticoagulation. Go AS, Hylek EM, Phillips KA, et al. Lip GY. Tap to unmute. Although AF increases the risk of stroke fivefold,12 this risk is not homogenous and depends on the presence or absence of specific stroke risk factors.13 These risk factors were incorporated into the simple CHADS2 score14 and used to artificially categorise patients as ‘low’, ’intermediate’ or ‘high’ risk. Dabigatran versus warfarin in patients with atrial fibrillation. They occurred at a rate of 1.69 % per year in patients assigned to warfarin, versus 1.53 % per year in patients assigned to dabigatran 110 mg (relative risk [RR] 0.91, 95 % confidence interval [CI] 0.74–1.11, p<0.001 for non-inferiority, p=0.34 for superiority compared with warfarin) and 1.11 % in patients assigned to dabigatran 150 mg (RR 0.66, 95 % CI 0.53–0.82, p<0.001 for non-inferiority and superiority compared with warfarin). When used in a low-dose twice-daily regimen, rivaroxaban also has a benefit for patients with a recent acute coronary syndrome (ACS),53 but the impact of the AF prophylaxis dose (20 mg once daily) plus dual antiplatelet therapy in the setting of an ACS has not been studied. Most thromboembolic complications of AF are eminently preventable with oral anticoagulation, and the increasing numbers of AF patients mean antithrombotic therapy is the most crucial management aspect of this common arrhythmia. PAC Atrial Fibrillation Anticoagulant clinical decision aid UKCPA Guidance of Safe Switching of Warfarin to NOACs Atrial Fibrillation Patient Information and Decision Aid Bulletin 224 - Choice of NOAC for Anticoagulation in Atrial Fibrillation Calculating Renal Function when Prescribing NOACs for non-valvular Atrial Fibrillation . A comparison of risk stratification schemes for stroke in 79,884 atrial fibrillation patients in general practice. Although warfarin has been proved to be highly efficacious as thromboprophylaxis, its limitations have negatively affected physicians’ willingness to prescribe – and patients’ willingness to receive – this effective treatment.9 This variability in prescribing habits for thromboprophylaxis has seen large numbers of patients left unprotected against stroke or inadequately protected with antiplatelet therapy,10 despite evidence highlighting that aspirin is an inferior option and carries its own substantial bleeding risk.11 The last decade has therefore seen an intensive search for novel oral anticoagulant drugs that could overcome the limitations associated with warfarin and see more patients with AF properly protected against stroke. Atrial fibrillation is the most common sustained cardiac arrhythmia, and estimates suggest its prevalence is increasing. Rivaroxaban in patients with a recent acute coronary syndrome. Although there is limited evidence informing us on how to deal with specific scenarios, such as peri-operative bridging and anticoagulant overdose, all the safety data available are very reassuring. These limitations of the CHADS2 score prompted efforts to establish a new schema that would be more inclusive of common stroke risk factors and would reliably identify ‘truly low-risk’ patients who do not require antithrombotic therapy, as well as reduce the number of patients at risk of stroke being denied oral anticoagulation. The aims of this prospective, … Arrhythmia & Electrophysiology Review 2012;1(1):12–6, Gregory YH Lip, University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham B18 7QH, UK. [new 2014] 1.5.3 Offer anticoagulation to people with a CHA 2 DS 2-VASc score of 2 or above, taking bleeding risk into account. Based on a literature search, pathogenesis of thromboembolism, risk assessment in patients, efficacy of anticoagulation therapy and its alternatives are discussed. You can download a PDF version for your personal record. Copy link. Table 1 outlines the risk factors that make up the CHA2DS2-VASc score. 860C Home. Patel MR, Mahaffey KW, Garg J, et al. Shopping. Most thromboembolic complications associated with AF can be prevented with anticoagulant therapy.8 For over fifty years, the only effective therapeutic option to prevent stroke in AF patients were vitamin K antagonists – i.e., warfarin. Copyright® 2021 Radcliffe Medical Media. All rights reserved. Atrial fibrillation and renal dysfunction often coexist, each disorder may predispose to the other and contribute to worsening prognosis. Van Walraven C, Jennings A, Oake N, et al. Rivaroxaban and apixaban have not been shown to cause dyspepsia, so may be the optimal option for patients unable to take dabigatran due to dyspepsia. Myocardial ischemic events in patients with atrial fibrillation treated with dabigatran or warfarin in the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial. European Heart Rhythm Association. Atrial fibrillation, Atrial fibrillation (AF) is the most common cardiac arrhythmia.1 Guidelines strongly and uniformly recommend anticoagulation in patients with AF and risk factors for cardioembolic events to mitigate the likelihood of stroke or thromboembolism.2–5 The benefits of oral anticoagulant therapy are directly proportional to the underlying stroke risk as measured by the congestive heart failure, hypertension, age, diabetes mellitus, prior stroke (CHADS2) or congestive heart failure or left ventricular systolic dysfuncti… Dabigatran is a competitive, direct and reversible inhibitor of thrombin. Gregory YH Lip has served as a consultant for Bayer, Astellas, Merck, Astr aZeneca, Sanofi, BMS/Pfizer, Daiichi-Sankyo, Biotronik, Portola and Boehringer Ingelheim; he has been on the speakers bureau for Bayer, BMS/Pfizer, Boehring er Ingelheim and Sanofi Aventis. If left untreated atrial fibrillation is a significant risk factor for stroke and other morbidities. The CC BY-NC option was not available for Radcliffe journals before 1 January 2019. publisher and the Radcliffe Group Ltd. the Management of Patients With Atrial Fibrillation” in areas where new evidence has emerged since its publication. Atrial fibrillation (AF) is an important public health problem affecting approximately 1% of the general population. Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events (ACTIVE W): A randomised controlled trial. Lin P. Reviewing the reality: why we need to change. There have been concerted efforts to unearth new drugs that would fulfil the criteria for the ideal anticoagulant and could represent a viable alternative to warfarin. White HD, Gruber M, Feyzi J, et al. The use of oral anticoagulation in patients with atrial fibrillation at moderate or high risk of stroke, estimated by established criteria, improves outcomes. Furthermore, anticoagulation monitoring is not required, so it is difficult to objectively evaluate a patient’s compliance with treatment. Apixaban demonstrated a benefit with regards to all-cause mortality compared with warfarin: rates of death from any cause were 3.52 % in the apixaban group versus 3.94 % in the warfarin group (HR 0.89, 95 % CI 0.80–0.99, p=0.047). Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Only articles clearly marked with the CC BY-NC logo are published with the Creative Commons by Attribution Licence. The general management strategies of haemorrhage on a novel anticoagulant may include stopping the drug, local measures to cease bleeding, intravenous fluid and blood product support, maintaining a diuresis for renally excreted drugs and the use of haemostatic agents such as prothrombin complex where necessary. Am Heart J. It may be possible for you to be treated by a GP, or you may be referred to a heart specialist (a cardiologist). Bleeding was similar in the two groups (event rate 14.91 % per 100 patient years with rivaroxaban versus 14.52 % with warfarin; HR 1.03, 95 % CI 0.96–1.11, p=0.442). The publication of this article was supported by Daiichi Sankyo Europe GmbH. oral anticoagulation, Atrial fibrillation (AF) is the most frequently encountered sustained arrhythmia with a prevalence of 0.5–10%, depending predominantly on age. Oxford University Hospitals NHS Foundation Trust group. The 75 mg twice daily dose of dabigatran approved by the US Food and Drug Administration in renal impairment was never actually studied in the RE-LY trial.47 A subgroup analysis of the RE-LY trial found that the rates of stroke and thromboembolism were increased in patients with impaired renal function. Objective To evaluate associations between oral anticoagulant (OAC) discontinuation and risk of ischaemic stroke (IS) among patients with atrial fibrillation (AF). One point is awarded for abnormal renal function and another point for abnormal liver function, and the same applies to drugs and/or alcohol. The authors certify that the manuscript represents their own work and are solely responsible for its content. Validation of clinical classification schemes for predicting stroke: Results from the National Registry of Atrial Fibrillation. About 13–26% of all acute ischaemic strokes are related to non-valvular atrial fibrillation, the most common cardiac arrhythmia globally. stroke prevention. The clinical implications of new oral anticoagulants: will the potential advantages be achieved? Drug discontinuation occurred less frequently: 25.3 % with apixaban versus 27.5 % with warfarin (p=0.001). Mant J, Hobbs FD, Fletcher K, et al. Risks of stroke and mortality associated with suboptimal anticoagulation in atrial fibrillation patients. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the Euro Heart Survey on Atrial Fibrillation. Most thromboembolic complications of AF are eminently preventable with oral anticoagulation, and the increasing numbers of AF patients mean antithrombotic therapy is the most crucial management aspect of this common arrhythmia. Both doses of dabigatran were associated with a significantly reduced risk of haemorrhagic stroke and intracranial haemorrhage when compared with warfarin. Factors associated with an increased risk of thromboembolic events in patients with atrial fibrillation (AF) include increasing age, rheumatic heart disease, poor left ventricular function, previous myocardial infarction, hypertension and a past history of a thromboembolic event. E : g.y.h.lip@bham.ac.uk. Sellers MB, Newby LK. Patients with atrial fibrillation (AF) are at increased thromboembolic risk, and they suffer more severe strokes with worse outcomes. Lip GY, Andreotti F, Fauchier L, et al. In addition, there has been advancement in the risk stratification of patients with AF. Rivaroxaban induced significantly less fatal bleeding and intracranial haemorrhage, but paradoxically significantly more patients on rivaroxaban required a blood transfusion or suffered a haemoglobin decrease of 2 g/dl or more. 1.5.2 Consider anticoagulation for men with a CHA 2 DS 2-VASc score of 1. Miyasaka Y, Barnes ME, Gersh BJ, et al. Self-monitoring can improve the quality of INR control33 and may bring the TTR closer to that achieved in clinical trials.34 Despite its unequivocal efficacy when properly used, warfarin has well documented limitations (see Table 3).35. For patients with atrial fibrillation who are receiving warfarin and require an elective operation or other elective invasive procedure, the need for bridging anticoagulation during perioperative interruption of warfarin treatment has long been uncertain.1-3 Each year, this common clinical scenario affects approximately one in six warfarin-treated patients with atrial fibrillation.4,5 Warfarin treatment is typically stopped 5 days before a… All three drugs also demonstrate positive bleeding profiles when compared with warfarin, especially intracranial haemorrhage and haemorrhagic stroke. Mega JL, Braunwald E, Wiviott SD, et al. Background: Atrial fibrillation (AF) is common in patients with end-stage renal disease (ESRD). BAS and JPP jointly interpreted the data and drafted and revised the manuscript. The CHADS2 score also classifies many patients as ‘intermediate-risk’,15 and there is evidence that warfarin is superior to aspirin for this group of patients.16 Similarly, the evidence suggests that aspirin is ineffective as stroke prevention for patients identified as ‘low-risk’ by CHADS2.17 Therefore the utilisation of the CHADS2 score in isolation would result in substantial numbers of patients at risk of stroke being undertreated. Low-dose aspirin for prevention of stroke in low-risk patients with atrial fibrillation: Japan Atrial Fibrillation Stroke Trial. A comparison of risk stratification schemes for stroke in 79,884 atrial fibrillation patients in general practice. As our experience with these new drugs grows, we will better be able to deal with the challenges they present. Rivaroxaban is an oral, reversible, direct factor Xa inhibitor.43 Although its half-life is 7–12 hours, factor Xa is inhibited for up to 24 hours. Atrial fibrillation (AF) poses a significant burden to patients, physicians, and healthcare systems globally. Compared with warfarin, dabigatran 150 mg was found to induce a small increase in the number of myocardial infarction events that was not statistically significant.40 Warfarin is protective against myocardial infarction,41 and the small numerical increase in myocardial infarction events with dabigatran must be interpreted in the context of the overall net clinical benefit of dabigatran over warfarin and the lack of any increase in new angina hospitalisations or revascularisations.42. The views and opinions expressed are those of the authors and not necessarily those of Daiichi Sankyo Europe GmbH. Lip GY, Lane DA. Atrial fibrillation and atrial flutter are important risk factors for stroke. BAS was funded by NIH T-32 training grant #5 T32 HL 7101-38. Furthermore, there is no evidence base to guide management in certain specific challenging clinical scenarios, such as an intentional overdose of anticoagulants, switching between warfarin and new agents, major bleeding, and anticoagulant bridging in the peri-operative period. It is not affiliated with or is Roser-Jones C, Becker RC. Stroke prevention with aspirin, warfarin and ximelagatran in patients with non-valvular atrial fibrillation: A systematic review and meta-analysis. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors In Atrial Fibrillation (ATRIA) study. You will encounter these medications in almost every care setting, and anticoagulation is definitely an area where prescribers look … Stroke patients with atrial fibrillation have a worse prognosis than patients without: data from the Austrian Stroke registry. In vitro and in vivo studies of the novel antithrombotic agent BAY 59-7939- an oral direct Factor Xa inhibitor. Atrial fibrillation increases the risk of stroke, which is a leading cause of death and disability worldwide. Lip GY, Nieuwlaat R, Pisters R, et al. European Heart Rhythm Association, European Association for Cardio-Thoracic Surgery, Camm AJ, Kirchhof P, Lip GY, et al. Vascular disease is defined as previous myocardial infarction, peripheral arterial disease or aortic plaque. An increased TTR is associated with less thromboembolism, less bleeding, fewer myocardial infarctions and fewer deaths.30,31 Small improvements in TTR translate into significant benefits,32 with a low TTR potentially obliterating the benefit of anticoagulation. If you are unable to import citations, please contact The trial’s population was generally high-risk, with 86 % of the total population possessing a CHADS2 score of 3 or higher. Hohnloser SH, Oldgren J, Yang S, et al. Study in Healthy Volunteers of the Reversion by Haemostatic Drugs of the Anticoagulant Effect of New Antithrombotics (REVNEWANTICO), Available at: Van Ryn J, Stangier J, Haertter S, et al.