CC BY 4.0 · TH Open 2021; 05(02): e176-e182
DOI: 10.1055/s-0041-1728670
Original Article

Atrial Fibrillation, Oral Anticoagulants, and Concomitant Active Cancer: Benefits and Risks

Adriano Atterman
1   Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden
,
Leif Friberg
1   Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden
,
Kjell Asplund
2   Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
,
Johan Engdahl
1   Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden
› Author Affiliations

Abstract

Aim To determine to what extent active cancer influences the benefit–risk relationship among patients with atrial fibrillation receiving oral anticoagulants for stroke prevention.

Methods In this cohort study of all patients with atrial fibrillation in the Swedish Patient register during 2006 to 2017, 8,228 patients with active cancer and 323,394 without cancer were followed up to 1 year after initiation of oral anticoagulants. Cox regression models, adjusting for confounders and the competing risk of death, were used to assess risk of cerebrovascular and bleeding events.

Results Among patients treated with oral anticoagulants, the risk for cerebrovascular events did not differ between cancer patients and noncancer patients (subhazard ratio [sHR]: 1.12, 95% confidence interval [CI]: 0.98–1.29). Cancer patients had a higher risk for bleedings (sHR: 1.69, CI: 1.56–1.82), but not for fatal bleedings (sHR: 1.17, CI: 0.80–1.70). Use of nonvitamin K oral anticoagulants was associated with lower risk of both cerebrovascular events and bleedings compared with warfarin.

Conclusion Patients with atrial fibrillation and active cancer appear to have similar net cerebrovascular benefit of oral anticoagulant treatment to patients without cancer, despite an increased risk of nonfatal bleedings. Use of nonvitamin K oral anticoagulants was associated with lower risk of all studied outcomes.

Supplementary Material



Publication History

Received: 04 May 2020

Accepted: 11 February 2021

Article published online:
01 June 2021

© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Mosarla RC, Vaduganathan M, Qamar A, Moslehi J, Piazza G, Giugliano RP. Anticoagulation strategies in patients with cancer: JACC review topic of the week. J Am Coll Cardiol 2019; 73 (11) 1336-1349
  • 2 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
  • 3 January CT, Wann LS, Calkins H. et al; Writing Group Members. 2019 AHA/ACC/HRS focused update of the 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Heart Rhythm 2019; 16 (08) e66-e93
  • 4 Atterman A, Friberg L, Asplund K, Engdahl J. Net benefit of oral anticoagulants in patients with atrial fibrillation and active cancer: a nationwide cohort study. Europace 2020; 22 (01) 58-65
  • 5 Cavallari I, Verolino G, Romano S, Patti G. Efficacy and safety of nonvitamin k oral anticoagulants in patients with atrial fibrillation and cancer: a study-level meta-analysis. Thromb Haemost 2020; 120 (02) 314-321
  • 6 Andersen KK, Olsen TS. Risk of ischemic and hemorrhagic strokes in occult and manifest cancers. Stroke 2018; 49 (07) 1585-1592
  • 7 Luengo-Fernandez R, Violato M, Candio P, Leal J. Economic burden of stroke across Europe: a population-based cost analysis. Eur Stroke J 2020; 5 (01) 17-25
  • 8 Smith JG, Platonov PG, Hedblad B, Engström G, Melander O. Atrial fibrillation in the Malmö Diet and Cancer study: a study of occurrence, risk factors and diagnostic validity. Eur J Epidemiol 2010; 25 (02) 95-102
  • 9 Köster M, Asplund K, Johansson Å, Stegmayr B. Refinement of Swedish administrative registers to monitor stroke events on the national level. Neuroepidemiology 2013; 40 (04) 240-246
  • 10 Ludvigsson JF, Andersson E, Ekbom A. et al. External review and validation of the Swedish national inpatient register. BMC Public Health 2011; 11: 450
  • 11 Friberg L, Skeppholm M. Usefulness of Health Registers for detection of bleeding events in outcome studies. Thromb Haemost 2016; 116 (06) 1131-1139
  • 12 Barlow L, Westergren K, Holmberg L, Talbäck M. The completeness of the Swedish Cancer Register: a sample survey for year 1998. Acta Oncol 2009; 48 (01) 27-33
  • 13 Wettermark B, Hammar N, Fored CM. et al. The new Swedish Prescribed Drug Register--opportunities for pharmacoepidemiological research and experience from the first six months. Pharmacoepidemiol Drug Saf 2007; 16 (07) 726-735
  • 14 Brooke HL, Talbäck M, Hörnblad J. et al. The Swedish cause of death register. Eur J Epidemiol 2017; 32 (09) 765-773
  • 15 Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ. 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. Chest 2010; 137 (02) 263-272
  • 16 Pisters R, Lane DA, Nieuwlaat R, de Vos CB, Crijns HJ, Lip GY. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest 2010; 138 (05) 1093-1100
  • 17 Aalen OO, Johansen S. An empirical transition matrix for non-homogeneous Markov chains based on censored observations. Scand Stat Theory Appl 1978; 5: 141-150
  • 18 Fine JP, Gray RJ. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc 1999; 94: 496-509
  • 19 Valachis A, Garmo H, Fredriksson I, Sund M, Lagerqvist B, Holmberg L. Bleeding risk in breast cancer patients during concomitant administration of warfarin and tamoxifen: a population-based nested case-control study. Breast J 2020; 26 (05) 981-987
  • 20 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
  • 21 D'Souza M, Smedegaard L, Madelaire C. et al. Atrial fibrillation and anticoagulation in patients with breast cancer. Scand Cardiovasc J 2019; 53 (05) 247-254
  • 22 Kamphuisen PW, Beyer-Westendorf J. Bleeding complications during anticoagulant treatment in patients with cancer. Thromb Res 2014; 133 (Suppl. 02) S49-S55
  • 23 Fanola CL, Ruff CT, Murphy SA. et al. Efficacy and safety of edoxaban in patients with active malignancy and atrial fibrillation: analysis of the ENGAGE AF - TIMI 48 trial. J Am Heart Assoc 2018; 7 (16) e008987
  • 24 Chen ST, Hellkamp AS, Becker RC. et al. Efficacy and safety of rivaroxaban vs. warfarin in patients with non-valvular atrial fibrillation and a history of cancer: observations from ROCKET AF. Eur Heart J Qual Care Clin Outcomes 2019; 5 (02) 145-152