Patients with cancer and atrial fibrillation treated with doacs: A prospective cohort study Maria Cristina Vedovati a, ⁎ ,1 , Michela Giustozzi a,1 , Paolo Verdecchia b,1 , Lucia Pierpaoli c,1 , Serenella Conti d,1 , Melina Verso a,1 , Francesco Di Filippo c,1 , Emanuela Marchesini a,1 , Giulio Bogliari a,1 , Giancarlo Agnelli a,1 , Cecilia Becattini a,1 a Internal and Cardiovascular Medicine - Stroke Unit, University of Perugia, Perugia, Italy b Department of Medicine, Hospital of Assisi, Assisi, Italy c Emergency Medicine, S. Maria Delle Croci Hospital, Ravenna, Italy d Division of Cardiology, S. Matteo degli Infermi Hospital, Spoleto, Italy abstract article info Article history: Received 25 April 2018 Received in revised form 19 June 2018 Accepted 27 July 2018 Available online xxxx Background: Limited data are available on the use of direct oral anticoagulants (DOACs) in patients with cancer and atrial fibrillation (AF). Methods: Consecutive patients with non-valvular AF treated with DOACs were enrolled in a prospective cohort with the aim of evaluating thromboembolic (ischemic stroke or transient ischemic attack or systemic embolism) and major bleeding (MB) events according to presence and type of cancer. The risk of study outcomes over time was compared using Kaplan-Meier method and log-rank test or Cox proportional hazards regression. Results: 2304 patients with non-valvular AF receiving DOACs were enrolled and 16 excluded: 2288 analysed of whom 289 (12.6%) had cancer. Gastrointestinal (21%), genitourinary (15%), prostate (15%), haematological (14%), breast (13%), and lung (8%) were the more frequent sites of cancer. After a mean follow-up of 451 days, thromboembolic events occurred in 2.1% and 0.8% patient-year of cancer and non-cancer patients (adjusted-HR 2.58, 95% CI 1.08–6.16, p = 0.033). The rate of MB was 6.6% and 3.0% patient- year in cancer and non-cancer patients (adjusted-HR 2.02, 95% CI 1.25–3.27, p = 0.004). The differences in bleeding were mainly accounted for by bleeding at gastrointestinal and genitourinary sites. No significant differ- ences were found concerning the rates of non-cancer-related mortality, fatal bleeding or fatal thrombotic events. Conclusions: In this study, the higher bleeding risk found in cancer compared to non-cancer patients was mainly due to an excess of bleeding at gastrointestinal and at genitourinary sites. Larger studies on the optimal manage- ment of cancer patients with AF are needed. © 2018 Published by Elsevier B.V. Keywords: Dabigatran Rivaroxaban Apixaban Atrial fibrillation Cancer Anticoagulants 1. Introduction Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and an important risk factor for stroke, heart failure and dementia [1–3]. The incidence of AF is known to be related to ageing, cardiovascular conditions (such as hypertension, heart failure, valvular disease) and non-cardiovascular conditions (such as diabetes, thyroid dysfunction, chronic pulmonary or kidney diseases). More recently, a correlation has been reported between AF and cancer [4,5]. The preva- lence of a concomitant history of cancer was reported up to 20% of AF patients in recent registries or cohort studies [6,7]. For several decades, vitamin K antagonists (VKAs) have been used in patients with AF to reduce the incidence of stroke or systemic embolism. Direct oral anticoagulants (DOACs) are being increasingly prescribed and are now recommended as the first choice anticoagulant agents in patients with non-valvular AF. In patients affected by both AF and cancer, antithrombotic treatment is challenging. Cancer patients are at high risk of both thromboembolic and bleeding events for the direct interaction of cancer with the coagulation system and for the effect of chemotherapy [5]. Clinically relevant data on antithrombotic treatment in cancer patients with AF are limited and only a position paper examines this topic [8]. Indeed, only a few number of cancer patients (those with presumed long life expectancy) were included in the DOAC phase III trials on AF. Post-hoc analyses from these studies led to inconclusive results concerning the thrombotic and bleeding risks of cancer and non-cancer patients as well as in cancer patients receiving DOACs or VKAs [9,10]. A retrospective analysis of a Danish cohort of AF patients on oral anticoagulant treatment showed a similar rate of International Journal of Cardiology xxx (2018) xxx–xxx ⁎ Corresponding author at: Internal and Cardiovascular Medicine - Stroke Unit, University of Perugia, Via G Dottori 1, 06129 Perugia, Italy. E-mail address: mariacristina.vedovati@unipg.it (M.C. Vedovati). 1 This author takes responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. IJCA-26805; No of Pages 6 https://doi.org/10.1016/j.ijcard.2018.07.138 0167-5273/© 2018 Published by Elsevier B.V. Contents lists available at ScienceDirect International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard Please cite this article as: M.C. Vedovati, et al., Patients with cancer and atrial fibrillation treated with doacs: A prospective cohort study, Int J Cardiol (2018), https://doi.org/10.1016/j.ijcard.2018.07.138