EDITORIAL

Non-vitamin K antagonist oral anticoagulationagents in anticoagulant naıve atrial fibrillationpatientsTorben Bjerregaard Larsen1,2*

1Department of Cardiology, Aalborg AF Study Group, Aalborg University Hospital, Aalborg DK-9000, Denmark; and2Thrombosis Research Unit, Department of Clinical Medicine, Faculty of Health, Aalborg University, DK-9000 Aalborg, Denmark

Received 31 July 2014; accepted after revision 2 August 2014

This editorial refers to ‘Non-vitamin K antagonist oral antic-oagulation agents (NOACs) in anticoagulant naıve atrialfibrillation patients: Danish Nationwide Descriptive Data2011–2013’ by J.B. Olesen et al., doi:10.1093/europace/euu225.

Atrial fibrillation (AF) is the commonest cardiac rhythm disorder andis associated with an increased risk of mortality and morbidity fromstroke and thromboembolism. Stroke prevention is essential forthe management of AF, and the landscape for stroke preventionhas changed with the availability of non-vitamin K antagonist oralanticoagulants (NOAC).

Several NOACs now exist, offering similar (or better) effective-ness, safety, and convenience to the vitamin K antagonists (VKAs);1

those with evidence from large randomized trials of stroke preven-tion in patients with AF fall into two drug classes: the direct thrombininhibitors (e.g. dabigatran), and the oral factor Xa inhibitors (e.g. riv-aroxaban, apixaban, and, most recently, edoxaban).

In this Journal, Jonas Bjerring Olesen and colleagues2 presentfindings from a large descriptive drug utilization study of all oralanticoagulation-naıve AF patients initiating oral anticoagulationfrom 22 August 2011 through 31 October 2013. The authors identi-fied more than 18 000 patients of whom 53% initiated warfarin treat-ment, 38% dabigatran, 7% rivaroxaban, and 1% apixaban. Oneinteresting finding was that patients prescribed rivaroxaban or apix-aban had a higher predicted stroke and bleeding risk compared withwarfarin or dabigatran initiators.

The European Society of Cardiology (ESC) Guidelines recom-mend oral anticoagulation for patients with a CHA2DS2-VAScscore of 2 or more (Class I recommendation) and are in favour ofthis therapy in patients with a CHA2DS2-VASc score of 1 (Class IIarecommendation).1 In this Danish study, all users of NOAC had

CHA2DS2-VASc scores higher than 2. While warfarin remains aviable option, the ESC Guidelines state that NOACs may be pre-ferred over warfarin, given their greater efficacy, safety, and conveni-ence. NovelOACs havebeen increasingly used in Europe, including inpatients with newly diagnosed AF. However, there are restrictions tothe use of NOACs in patients with a various degree of renal impair-ment, and each of these agents has been issued with a set of specificrules relating to renal function.3 In this study on new users by Olesenet al., it is therefore very reassuring that users of NOAC were feweramong patients with chronic kidney disease in accordance with theESC Guidelines, mostnotably fordabigatran (80% of this drug is elimi-nated renally). However, a substantial proportion of dabigatran initia-tors are patients who are switched from warfarin, so-called switchers,and they differ substantially from new users in terms of co-morbidities and stroke risk.4 One must take this into considerationwhen data are interpreted. Indeed, another Danish drug utilizationstudy recently showed that a large proportion of NOAC usersswitch back to VKA within a short timeframe.5 Reasons for thiswere not clear.

In observational studies of intended drug effects or safety, substan-tial confounding (by indication) is to be expected since the perceivedrisk is often closely related to the physician’s choice of treatment.Where there is confounding, there is also the possibility of residualconfounding. Taken to the extreme, heterogeneity in risk factors(measured or unmeasured) between treatment groups in key riskfactors might be a possible explanation for observed associationsor differences. Therefore, a careful choice of methods and principlesthat can mitigate confounding is imperative. Post-marketing cohortstudies can indeed contribute to our understanding of drug safetyand effectiveness over time. As an example, prescribing informationand our knowledge about NOAC drug characteristics show differ-ences in terms of how patients received different NOACs.

The opinions expressed in this article are not necessarily those of the Editors of Europace or of the European Society of Cardiology.

* Corresponding author. Tel: +45 97 66 45 40; Fax: +45 97 66 45 42. E-mail address: tobl@rn.dk

Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2014. For permissions please email: journals.permissions@oup.com.

Europacedoi:10.1093/europace/euu223

Europace Advance Access published October 23, 2014by guest on O

ctober 27, 2014D

ownloaded from

However, we need studies that actually compare outcomes as aconsequence of these differences.

Novel OACs have heralded a new era in anticoagulation forpatients with AF. To ensure that patients derive the maximumbenefit from therapy, understanding the differences betweenNOACs and VKAs and the practical implications for day-to-day prac-tice is critical. However, clinical experience of NOACs outside oftrials remains limited, and further insights into appropriate use willundoubtedly become apparent as these agents are prescribedmore widely.

Conflict of interest: T.B.L. has been an investigator for JanssenScientific Affairs and Boehringer Ingelheim, and served on speakerbureaux for Bayer, Bristol-Myers Squibb/Pfizer, Janssen Pharmaceu-ticals, Takeda, Roche Diagnostics, and Boehringer Ingelheim.

References1. Camm AJ, Lip GYH, De Caterina R, Savelieva I, Atar D, Hohnloser SH et al. 2012

focused update of the ESC Guidelines for the management of atrial fibrillation: anupdate of the 2010 ESC Guidelines for the management of atrial fibrillation—developed with the special contribution of the European Heart Rhythm Association.Europace 2012;14:1385–413.

2. Olesen JB, Sørensen R, Hansen ML, Lamberts M, Weeke P, Mikkelsen AP et al.Non-vitamin k antagonist oral anticoagulation agents in anticoagulant naıve atrialfibrillation patients: Danish nationwide descriptive data 2011–2013. Europace 2014;doi:10.1093/europace/euu225.

3. Savelieva I, Camm AJ. Practical considerations for using novel oral anticoagulants inpatients with atrial fibrillation. Clin Cardiol 2014;37:32–47.

4. Larsen TB, Gorst-Rasmussen A, Rasmussen LH, Skjøth F, Rosenzweig M, Lip GYH.Bleeding events among new starters and switchers to dabigatran compared withwarfarin in atrial fibrillation. Am J Med 2014;127:650–6.e5.

5. Pottegard A, Poulsen BK, Larsen MD, Hallas J. Dynamics of vitamin K-antagonist andnew oral anticoagulants use in atrial fibrillation: A Danish drug utilization study.J Thromb Haemost 2014; doi: 10.1111/jth.12662.

EditorialPage 2 of 2

by guest on October 27, 2014

Dow

nloaded from