Atrial Fibrillation and Malignancy: The Clinical Performance of Non–Vitamin K Oral Anticoagulants—A Systematic Review

Abstract

Atrial fibrillation (AF) is commonly diagnosed in the setting of active cancer. Because of an increased risk of either thromboembolic events or bleeding, the decision to initiate therapeutic anticoagulation in patients with active cancer can be challenging. Moreover, little is still known about the optimal anticoagulation therapy in the setting of AF and cancer, and no guidelines are as yet available. Considering that nonvitamin K antagonist oral anticoagulants (NOACs) are recommended as alternatives to vitamin K antagonists for stroke prevention in AF patients with CHA₂DS_2-VASc score ≥2, the authors performed a systematic review of the current literature to describe the efficacy and safety of NOACs in AF patients with malignancy.

Keywords

atrial fibrillation - cancer - NOACs - dabigatran - apixaban - rivaroxaban - edoxaban - bleeding - stroke - embolism

• References

• 1 Chugh SS, Havmoeller R, Narayanan K. , et al. Worldwide epidemiology of atrial fibrillation: a Global Burden of Disease 2010 Study. Circulation 2014; 129 (08) 837-847
• 2 Mann DL, Krone RJ. Cardiac disease in cancer patients: an overview. Prog Cardiovasc Dis 2010; 53 (02) 80-87
• 3 Hu YF, Liu CJ, Chang PM. , et al. Incident thromboembolism and heart failure associated with new-onset atrial fibrillation in cancer patients. Int J Cardiol 2013; 165 (02) 355-357
• 4 Lainscak M, Dagres N, Filippatos GS, Anker SD, Kremastinos DT. Atrial fibrillation in chronic non-cardiac disease: where do we stand?. Int J Cardiol 2008; 128 (03) 311-315
• 5 Guzzetti S, Costantino G, Fundarò C. Systemic inflammation, atrial fibrillation, and cancer. Circulation 2002; 106 (09) e40 , author reply e40
• 6 Kearon C, Akl EA, Ornelas J. , et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest 2016; 149 (02) 315-352
• 7 Connolly SJ, Ezekowitz MD, Yusuf S. , et al; RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361 (12) 1139-1151
• 8 Patel MR, Mahaffey KW, Garg J. , et al; ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011; 365 (10) 883-891
• 9 Granger CB, Alexander JH, McMurray JJ. , et al; ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011; 365 (11) 981-992
• 10 Giugliano RP, Ruff CT, Braunwald E. , et al; ENGAGE AF-TIMI 48 Investigators. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2013; 369 (22) 2093-2104
• 11 Kirchhof P, Benussi S, Kotecha D. , et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Europace 2016; 18 (11) 1609-1678
• 12 Wells G, Shea B, O'Connell D. , et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. . Available at: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp . Accessed February 12, 2018
• 13 Ording AG, Horváth-Puhó E, Adelborg K, Pedersen L, Prandoni P, Sørensen HT. Thromboembolic and bleeding complications during oral anticoagulation therapy in cancer patients with atrial fibrillation: a Danish nationwide population-based cohort study. Cancer Med 2017; 6 (06) 1165-1172
• 14 Flack KF, Desai J, Kolb JM. , et al. Major gastrointestinal bleeding often is caused by occult malignancy in patients receiving warfarin or dabigatran to prevent stroke and systemic embolism from atrial fibrillation. Clin Gastroenterol Hepatol 2017; 15 (05) 682-690
• 15 Melloni C, Dunning A, Granger CB. , et al. Efficacy and safety of apixaban versus warfarin in patients with atrial fibrillation and a history of cancer: insights from the ARISTOTLE trial. Am J Med 2017; 130 (12) 1440-1448.e1
• 16 Laube ES, Yu A, Gupta D. , et al. Rivaroxaban for stroke prevention in patients with nonvalvular atrial fibrillation and active cancer. Am J Cardiol 2017; 120 (02) 213-217
• 17 Russo V, Rago A, Papa AA. , et al. Use of non-vitamin k antagonist oral anticoagulants in atrial fibrillation patients with malignancy: clinical practice experience in a single institution and literature review. Semin Thromb Hemost 2018; 44 (04) 370-376
• 18 Ianotto JC, Couturier MA, Galinat H. , et al. Administration of direct oral anticoagulants in patients with myeloproliferative neoplasms. Int J Hematol 2017; 106 (04) 517-521
• 19 Schulman S, Kearon C. ; Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 2005; 3 (04) 692-694
• 20 Falanga A, Marchetti M, Russo L. The mechanisms of cancer-associated thrombosis. Thromb Res 2015; 135 (Suppl. 01) S8-S11
• 21 Trujillo-Santos J, Martos FM, Font C. , et al. Analysis of clinical factors affecting the rates of fatal pulmonary embolism and bleeding in cancer patients with venous thromboembolism. Heliyon (Lond) 2017; 3 (01) e00229
• 22 Ruff CT, Giugliano RP, Braunwald E. , et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet 2014; 383 (9921): 955-962