Download PDF
Thromb Haemost 2020; 120(02): 314-321
DOI: 10.1055/s-0039-3400300
Stroke, Systemic or Venous Thromboembolism
Georg Thieme Verlag KG Stuttgart · New York

Efficacy and Safety of Nonvitamin K Oral Anticoagulants in Patients with Atrial Fibrillation and Cancer: A Study-Level Meta-Analysis

Ilaria Cavallari
1   Department of Cardiovascular Sciences, Campus Bio-Medico University of Rome, Rome, Italy
,
Giuseppe Verolino
1   Department of Cardiovascular Sciences, Campus Bio-Medico University of Rome, Rome, Italy
,
Silvio Romano
2   Department of Life, Health & Environmental Sciences, University of L'Aquila, L'Aquila, Italy
,
Giuseppe Patti
3   Department of Translational Medicine, University of Eastern Piedmont, Maggiore della Carità Hospital, Novara, Italy
› Author Affiliations
Further Information

Publication History

15 July 2019

21 September 2019

Publication Date:
30 November 2019 (online)

Also available at
    Permissions and Reprints

Letter to:

Oral Anticoagulant Treatment in Patients with Atrial Fibrillation and CancerThromb Haemost 2020; 120(02): 194-196
DOI: 10.1055/s-0039-3402809

Abstract

Objectives In this study-level meta-analysis, we evaluated the clinical outcome with nonvitamin K antagonist oral anticoagulants (NOACs) versus vitamin K antagonists (VKAs) in atrial fibrillation (AF) patients with cancer.

Background Anticoagulation in AF patients with cancer is challenging given the coexistence of elevated thrombotic and bleeding risk. The efficacy and safety of NOACs in this setting remain unclear.

Methods We included three randomized trials in our primary analysis (N = 2,661 patients) and three observational studies in our secondary, confirmatory analysis (N = 21,112 patients). Outcome measures were: the composite of any stroke or systemic embolism, ischemic stroke, venous thromboembolism, major bleeding, intracranial bleeding; and all-cause death. Mean follow-up duration was 2.2 years.

Results In the primary analysis, the use of NOACs was associated with similar incidence of stroke/systemic embolism (odds ratio [OR] 0.70, 95% confidence interval 0.45–1.09; p = 0.11), ischemic stroke (OR 0.71, 0.31–1.64; p = 0.42), venous thromboembolism (OR 0.91, 0.33–2.53; p = 0.86), all-cause death (OR 1.02, 0.72–1.42; p = 0.93), and major bleeding (OR 0.81, 0.61–1.06; p = 0.13) compared with VKAs. The occurrence of intracranial bleeding was significantly lower in the NOACs versus VKAs group (OR 0.11, 0.02–0.63; p = 0.01). These results were overall confirmed in the secondary analysis, where there was additionally a significant reduction of stroke/systemic embolism, ischemic stroke, and venous thromboembolism with NOACs.

Conclusion In AF patients with malignancy, NOACs appear at least as effective as VKAs in preventing thrombotic events and reduce intracranial bleeding. NOACs may represent a valid and more practical alternative to VKAs in this setting of high-risk patients.

Keywords

atrial fibrillation - cancer - anticoagulation - stroke - bleeding

Supplementary Material

 

  • References

  • 1 Kirchhof P, Benussi S, Kotecha D. , et al. 2016 ESC guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Rev Española Cardiol (English ed.) 2017; 70 (01) 50
    PubMedSearch in Google Scholar
  • 2 Go AS, Hylek EM, Phillips KA. , et al. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) study. JAMA 2001; 285 (18) 2370-2375
    CrossrefPubMedSearch in Google Scholar
  • 3 Hart RG, Pearce LA, McBride R, Rothbart RM, Asinger RW. ; The Stroke Prevention in Atrial Fibrillation (SPAF) Investigators. Factors associated with ischemic stroke during aspirin therapy in atrial fibrillation: analysis of 2012 participants in the SPAF I-III clinical trials. Stroke 1999; 30 (06) 1223-1229
    CrossrefPubMedSearch in Google Scholar
  • 4 Miyasaka Y, Barnes ME, Gersh BJ. , et al. Secular trends in incidence of atrial fibrillation in Olmsted County, Minnesota, 1980 to 2000, and implications on the projections for future prevalence. Circulation 2006; 114 (02) 119-125
    CrossrefPubMedSearch in Google Scholar
  • 5 Perera V, Bajorek BV, Matthews S, Hilmer SN. The impact of frailty on the utilisation of antithrombotic therapy in older patients with atrial fibrillation. Age Ageing 2009; 38 (02) 156-162
    PubMedSearch in Google Scholar
  • 6 Melloni C, Shrader P, Carver J. , et al; ORBIT-AF Steering Committee. Management and outcomes of patients with atrial fibrillation and a history of cancer: the ORBIT-AF registry. Eur Heart J Qual Care Clin Outcomes 2017; 3 (03) 192-197
    CrossrefPubMedSearch in Google Scholar
  • 7 Steffel J, Verhamme P, Potpara TS. , et al; ESC Scientific Document Group. The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. Eur Heart J 2018; 39 (16) 1330-1393
    CrossrefPubMedSearch in Google Scholar
  • 8 O'Neal WT, Claxton JS, Sandesara PB. , et al. Provider specialty, anticoagulation, and stroke risk in patients with atrial fibrillation and cancer. J Am Coll Cardiol 2018; 72 (16) 1913-1922
    CrossrefPubMedSearch in Google Scholar
  • 9 Suter TM, Ewer MS. Cancer drugs and the heart: importance and management. Eur Heart J 2013; 34 (15) 1102-1111
    CrossrefPubMedSearch in Google Scholar
  • 10 Hutten BA, Prins MH, Gent M, Ginsberg J, Tijssen JG, Büller HR. Incidence of recurrent thromboembolic and bleeding complications among patients with venous thromboembolism in relation to both malignancy and achieved international normalized ratio: a retrospective analysis. J Clin Oncol 2000; 18 (17) 3078-3083
    CrossrefPubMedSearch in Google Scholar
  • 11 Veltkamp R, Hacke W. Neue orale Antikoagulanzien beim Vorhofflimmern. Nervenarzt 2011; 82 (02) 180-189
    CrossrefPubMedSearch in Google Scholar
  • 12 Moher D, Liberati A, Tetzlaff J, Altman DG. ; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 2009; 339 (01) b2535
    CrossrefPubMedSearch in Google Scholar
  • 13 Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 2010; 25: 603-605
    CrossrefPubMedSearch in Google Scholar
  • 14 Higgins JPT, Altman DG, Gøtzsche PC. , et al; Cochrane Bias Methods Group; Cochrane Statistical Methods Group. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ 2011; 343: d5928
    CrossrefPubMedSearch in Google Scholar
  • 15 Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 1959; 22 (04) 719-748
    PubMedSearch in Google Scholar
  • 16 Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003; 327 (7414): 557-560
    CrossrefPubMedSearch in Google Scholar
  • 17 Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics 1994; 50 (04) 1088-1101
    CrossrefPubMedSearch in Google Scholar
  • 18 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
    CrossrefPubMedSearch in Google Scholar
  • 19 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
    CrossrefPubMedSearch in Google Scholar
  • 20 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
    PubMedSearch in Google Scholar
  • 21 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
    CrossrefPubMedSearch in Google Scholar
  • 22 Kim K, Lee YJ, Kim TH. , et al. Effect of non-vitamin K antagonist oral anticoagulants in atrial fibrillation patients with newly diagnosed cancer. Korean Circ J 2018; 48 (05) 406-417
    CrossrefPubMedSearch in Google Scholar
  • 23 Shah S, Norby FL, Datta YH. , et al. Comparative effectiveness of direct oral anticoagulants and warfarin in patients with cancer and atrial fibrillation. Blood Adv 2018; 2 (03) 200-209
    CrossrefPubMedSearch in Google Scholar
  • 24 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
    PubMedSearch in Google Scholar
  • 25 Caine GJ, Stonelake PS, Lip GYH, Kehoe ST. The hypercoagulable state of malignancy: pathogenesis and current debate. Neoplasia 2002; 4 (06) 465-473
    CrossrefPubMedSearch in Google Scholar
  • 26 Cronin-Fenton DP, Søndergaard F, Pedersen LA. , et al. Hospitalisation for venous thromboembolism in cancer patients and the general population: a population-based cohort study in Denmark, 1997-2006. Br J Cancer 2010; 103 (07) 947-953
    CrossrefPubMedSearch in Google Scholar
  • 27 Blom JW, Doggen CJM, Osanto S, Rosendaal FR. Malignancies, prothrombotic mutations, and the risk of venous thrombosis. JAMA 2005; 293 (06) 715-722
    CrossrefPubMedSearch in Google Scholar
  • 28 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
    CrossrefPubMedSearch in Google Scholar
  • 29 Walker AJ, Card TR, West J, Crooks C, Grainge MJ. Incidence of venous thromboembolism in patients with cancer - a cohort study using linked United Kingdom databases. Eur J Cancer 2013; 49 (06) 1404-1413
    CrossrefPubMedSearch in Google Scholar
  • 30 Horsted F, West J, Grainge MJ. Risk of venous thromboembolism in patients with cancer: a systematic review and meta-analysis. PLoS Med 2012; 9 (07) e1001275
    CrossrefPubMedSearch in Google Scholar
  • 31 Steffel J, Verhamme P, Potpara TS. , et al; ESC Scientific Document Group. The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. Eur Heart J 2018; 39 (16) 1330-1393
    CrossrefPubMedSearch in Google Scholar
  • 32 Bona RD, Sivjee KY, Hickey AD, Wallace DM, Wajcs SB. The efficacy and safety of oral anticoagulation in patients with cancer. Thromb Haemost 1995; 74 (04) 1055-1058
    Thieme ConnectPubMedSearch in Google Scholar
  • 33 January CT, Wann LS, Alpert JS. , et al; ACC/AHA Task Force Members. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society. Circulation 2014; 130 (23) 2071-2104
    CrossrefPubMedSearch in Google Scholar
  • 34 Hendrie PC, Garcia DA. Are new oral anticoagulants ready for use in patients with cancer?. J Natl Compr Canc Netw 2013; 11 (11) 1446-1449
    CrossrefPubMedSearch in Google Scholar
  • 35 Lyman GH, Kuderer NM. When to offer thromboprophylaxis to patients with advanced pancreatic cancer: shedding light on the path forward. J Clin Oncol 2015; 33 (18) 1995-1997
    CrossrefPubMedSearch in Google Scholar
  • 36 Raskob GE, van Es N, Verhamme P. , et al; Hokusai VTE Cancer Investigators. Edoxaban for the treatment of cancer-associated venous thromboembolism. N Engl J Med 2018; 378 (07) 615-624
    CrossrefPubMedSearch in Google Scholar
  • 37 Carrier M, Abou-Nassar K, Mallick R. , et al; AVERT Investigators. Apixaban to prevent venous thromboembolism in patients with cancer. N Engl J Med 2019; 380 (08) 711-719
    CrossrefPubMedSearch in Google Scholar
  • 38 Puurunen MK, Gona PN, Larson MG, Murabito JM, Magnani JW, O'Donnell CJ. Epidemiology of venous thromboembolism in the Framingham Heart Study. Thromb Res 2016; 145: 27-33
    CrossrefPubMedSearch in Google Scholar
  • 39 Chee CE, Ashrani AA, Marks RS. , et al. Predictors of venous thromboembolism recurrence and bleeding among active cancer patients: a population-based cohort study. Blood 2014; 123 (25) 3972-3978
    CrossrefPubMedSearch in Google Scholar
  • 40 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
    CrossrefPubMedSearch in Google Scholar