ORIGINAL ARTICLE Frequent and possibly inappropriate use of combination therapy with an oral anticoagulant and antiplatelet agents in patients with atrial fibrillation in Europe Raffaele De Caterina, 1,2 Bettina Ammentorp, 3 Harald Darius, 4 Jean-Yves Le Heuzey, 5 Giulia Renda, 1 Richard John Schilling, 6 Tessa Schliephacke, 3 Paul-Egbert Reimitz, 3 Josef Schmitt, 3 Christine Schober, 3 José Luis Zamorano, 7 Paulus Kirchhof, 8,9 for the PREFER in AF Registry Investigators ▸ Additional material is published online only. To view please visit the journal online (http://dx.doi.org/10.1136/ heartjnl-2014-305486). For numbered affiliations see end of article. Correspondence to Professor Raffaele De Caterina, Institute of Cardiology, “G. d’Annunzio” University— Chieti, C/o Ospedale SS. Annunziata, Via dei Vestini, Chieti 66013, Italy; rdecater@unich.it Received 6 January 2014 Revised 30 June 2014 Accepted 2 July 2014 To cite: De Caterina R, Ammentorp B, Darius H, et al. Heart Published Online First: [ please include Day Month Year] doi:10.1136/ heartjnl-2014-305486 ABSTRACT Purpose Combined oral anticoagulant (OAC) and antiplatelet (AP) therapy is generally discouraged in atrial fibrillation (AF) outside of acute coronary syndromes or stenting because of increased bleeding. We evaluated its frequency and possible reasons in a contemporary European AF population. Methods The PREvention oF thromboembolic events– European Registry in Atrial Fibrillation (PREFER in AF) prospectively enrolled AF patients in France, Germany, Austria, Switzerland, Italy, Spain and the UK from January 2012 to January 2013. We evaluated patterns of combined VKA-AP therapy in this population. Results Out of 7243 patients enrolled, 5170 (71.4%) were treated with OAC alone, 808 (11.2%) with AP alone and 791 (10.9%) with a combination of OAC and one (dual) or two AP (triple combination therapy). Compared with patients only prescribed OAC, patients on combination treatment had similar Body Mass Index, but more frequently diabetes (p<0.05), dyslipidaemia ( p<0.01), coronary heart disease (54.2 vs 18.6%; p<0.01) or peripheral arterial disease (10.2 vs 3.7%; p<0.01). Accordingly, they had a higher mean CHA 2 DS 2 VASc (3.7 vs 3.4), and HAS-BLED (2.7 vs 1.9) scores (for both, p<0.01). Of the 660 patients on dual AP+OAC combination therapy, 629 (95.3%) did not have an accepted indication. Out of the 105 patients receiving triple combination therapy, 67 (63.8%) did not have an accepted indication. Conclusions The combined use of OAC and AP therapy is not uncommon in AF, largely inappropriate, explained by the coexistence of coronary or peripheral arterial disease, and not influenced by considerations on the risk of bleeding. INTRODUCTION Atrial fibrillation (AF) and coronary heart disease (CHD) are common and important causes of mor- bidity and mortality, 12 sharing many risk factors, 1 and frequently coexisting. It has indeed been esti- mated that 20% of the AF population has concomi- tant CHD. 3 Atrial fibrillation also frequently coexists with cerebrovascular disease 4 and periph- eral arterial disease (PAD), 4 other manifestations of systemic atherosclerosis. Most patients with AF, with or without coexisting CHD are in need of oral anticoagulant (OAC) therapy with either a vitamin K antagonist (VKA) or one of the non-vitamin K antagonist oral anticoagu- lants (NOAC) to prevent AF-related strokes. 5–7 On the other hand, the main antithrombotic prophy- laxis in patients with evidence of vascular disease is antiplatelet therapy. This is carried on, in the vast majority of cases, with aspirin alone in stable patients; or a combination of aspirin with an ADP P2Y12 inhibitor—mostly clopidogrel—in the first months after an acute event or a stent implant- ation. 8 9 However, the optimal antithrombotic prophylaxis when AF and vascular disease coexist is still a matter of discussion. Dual antiplatelet therapy is considered appropriate to prevent stent throm- bosis after a recent stent implantation (usually for 1 month after implantation of a bare-metal stent (BMS), and 3–6 months after a drug-eluting stent). 10 Furthermore, dual antiplatelet therapy can reduce recurrent ischaemic events after an acute cor- onary syndrome (ACS) 11 12 and prevent stent thrombosis after stenting better than VKAs. 13 Conversely, VKAs are superior to dual antiplatelet therapy to prevent stroke in AF patients. 14 In case of coexisting AF and stable vascular disease (CHD, cerebrovascular disease and PAD) in the absence of a recent stenting and a recent ACS, the current ESC Guidelines in AF 1 7 recommend anticoagulant therapy only, as this proved effective in assuring sec- ondary prophylaxis from vascular events, 15 and as the combination of an anticoagulant (VKA in most cases) with aspirin considerably increases the risk of bleeding with uncertain efficacy/safety advantages. 16 Here, we analysed the baseline data from a large, contemporary European registry of AF patients (a) to describe the patterns of antithrombotic treat- ments in patients with AF and (b) to assess suspected reasons for the pattern of combined OAC and antiplatelet drug treatment, and its appropriateness according to ESC guidelines in five representative European regions in such settings. De Caterina R, et al. Heart 2014;0:1–11. doi:10.1136/heartjnl-2014-305486 1 Arrhythmias and sudden death Heart Online First, published on August 8, 2014 as 10.1136/heartjnl-2014-305486 Copyright Article author (or their employer) 2014. Produced by BMJ Publishing Group Ltd (& BCS) under licence. group.bmj.com on August 8, 2014 - Published by heart.bmj.com Downloaded from