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Open Access 06-09-2024 | Atrial Fibrillation | Original Research Article

Impact of Newly Diagnosed Cancer on Bleeding Events in Patients with Atrial Fibrillation Treated with Direct Oral Anticoagulants

Authors: Francesco Angeli, Luca Bergamaschi, Matteo Armillotta, Angelo Sansonetti, Andrea Stefanizzi, Lisa Canton, Francesca Bodega, Nicole Suma, Sara Amicone, Damiano Fedele, Davide Bertolini, Andrea Impellizzeri, Francesco Pio Tattilo, Daniele Cavallo, Lorenzo Bartoli, Ornella Di Iuorio, Khrystyna Ryabenko, Marcello Casuso Alvarez, Virginia Marinelli, Claudio Asta, Mariachiara Ciarlantini, Giuseppe Pastore, Andrea Rinaldi, Daniela Paola Pomata, Ilaria Caldarera, Carmine Pizzi

Published in: American Journal of Cardiovascular Drugs

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Abstract

Background

In patients with atrial fibrillation (AF), the association between cancer and cardioembolic or bleeding risk during oral anticoagulant therapy still remains unclear.

Purpose

We aimed to assess the impact of cancer present at baseline (CB) or diagnosed during follow-up (CFU) on bleeding events in patients treated with direct oral anticoagulants (DOACs) for non-valvular AF (NVAF) compared with patients without CB or CFU, respectively.

Methods

All consecutive patients with NVAF treated with DOACs for stroke prevention were enrolled between January 2017 and March 2019. Primary outcomes were bleeding events or cardiovascular death, non-fatal stroke and non-fatal myocardial infarction, and the composite endpoint between patients with and without CB and between patients with and without CB.

Results

The study population comprised 1170 patients who were followed for a mean time of 21.6 ± 9.5 months. Overall, 81 patients (6.9%) were affected by CB, while 81 (6.9%) were diagnosed with CFU. Patients with CFU were associated with a higher risk of bleeding events and major bleeding compared with patients without CFU. Such an association was not observed between the CB and no CB populations. In multivariate analysis adjusted for anemia, age, creatinine, CB and CFU, CFU but not CB remained an independent predictor of overall and major bleeding (hazard ratio [HR] 2.67, 95% confidence interval [CI] 1.8–3.89, p < 0.001; HR 3.02, 95% CI 1.6–3.81, p = 0.001, respectively).

Conclusion

During follow-up, newly diagnosed primitive or metastatic cancer in patients with NVAF taking DOACs is a strong predictor of major bleeding regardless of baseline hemorrhagic risk assessment. In contrast, such an association is not observed with malignancy at baseline. Appropriate diagnosis and treatment could therefore reduce the risk of cancer-related bleeding.
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Literature
1.
go back to reference Cheng W-L, Kao Y-H, Chen S-A, Chen Y-J. Pathophysiology of cancer therapy-provoked atrial fibrillation. Int J Cardiol. 2016;219:186–94.CrossRefPubMed Cheng W-L, Kao Y-H, Chen S-A, Chen Y-J. Pathophysiology of cancer therapy-provoked atrial fibrillation. Int J Cardiol. 2016;219:186–94.CrossRefPubMed
2.
go back to reference O’Neal WT, Lakoski SG, Qureshi W, et al. Relation between cancer and atrial fibrillation (from the reasons for geographic and racial differences in stroke study). Am J Cardiol. 2015;115:1090–4.CrossRefPubMedPubMedCentral O’Neal WT, Lakoski SG, Qureshi W, et al. Relation between cancer and atrial fibrillation (from the reasons for geographic and racial differences in stroke study). Am J Cardiol. 2015;115:1090–4.CrossRefPubMedPubMedCentral
3.
go back to reference Farmakis D, Parissis J, Filippatos G. Insights into onco-cardiology. J Am Coll Cardiol. 2014;63:945–53.CrossRefPubMed Farmakis D, Parissis J, Filippatos G. Insights into onco-cardiology. J Am Coll Cardiol. 2014;63:945–53.CrossRefPubMed
4.
go back to reference Guzzetti S, Costantino G, Fundarò C. Systemic inflammation, atrial fibrillation, and cancer. Circulation. 2002;106(9):e40. Guzzetti S, Costantino G, Fundarò C. Systemic inflammation, atrial fibrillation, and cancer. Circulation. 2002;106(9):e40.
6.
go back to reference Erichsen R, Christiansen CF, Frøslev T, Jacobsen J, Sørensen HT. Intravenous bisphosphonate therapy and atrial fibrillation/flutter risk in cancer patients: a nationwide cohort study. Br J Cancer. 2011;105:881–3.CrossRefPubMedPubMedCentral Erichsen R, Christiansen CF, Frøslev T, Jacobsen J, Sørensen HT. Intravenous bisphosphonate therapy and atrial fibrillation/flutter risk in cancer patients: a nationwide cohort study. Br J Cancer. 2011;105:881–3.CrossRefPubMedPubMedCentral
7.
go back to reference Lateef N, Kapoor V, Ahsan MJ, et al. Atrial fibrillation and cancer; understanding the mysterious relationship through a systematic review. J Community Hosp Intern Med Perspect. 2020;10:127–32.CrossRefPubMedPubMedCentral Lateef N, Kapoor V, Ahsan MJ, et al. Atrial fibrillation and cancer; understanding the mysterious relationship through a systematic review. J Community Hosp Intern Med Perspect. 2020;10:127–32.CrossRefPubMedPubMedCentral
8.
go back to reference Foà A, Paolisso P, Bergamaschi L, et al. Clues and pitfalls in the diagnostic approach to cardiac masses: are pseudo-tumours truly benign? Eur J Prev Cardiol. 2022;29:e102–4.CrossRefPubMed Foà A, Paolisso P, Bergamaschi L, et al. Clues and pitfalls in the diagnostic approach to cardiac masses: are pseudo-tumours truly benign? Eur J Prev Cardiol. 2022;29:e102–4.CrossRefPubMed
9.
10.
go back to reference Angeli F, Fabrizio M, Paolisso P, et al. Cardiac masses: classification, clinical features and diagnostic approach [in Italian]. G Ital Cardiol (Rome). 2022;23:620–30.PubMed Angeli F, Fabrizio M, Paolisso P, et al. Cardiac masses: classification, clinical features and diagnostic approach [in Italian]. G Ital Cardiol (Rome). 2022;23:620–30.PubMed
11.
go back to reference Paolisso P, Foà A, Magnani I, et al. Development and validation of a diagnostic echocardiographic mass score in the approach to cardiac masses. JACC Cardiovasc Imaging. 2022;15(11):2010–2.CrossRefPubMed Paolisso P, Foà A, Magnani I, et al. Development and validation of a diagnostic echocardiographic mass score in the approach to cardiac masses. JACC Cardiovasc Imaging. 2022;15(11):2010–2.CrossRefPubMed
12.
go back to reference Paolisso P, Foà A, Bergamaschi L, et al. Echocardiographic markers in the diagnosis of cardiac masses. J Am Soc Echocardiogr. 2023;36(5):464-473.e2.CrossRefPubMed Paolisso P, Foà A, Bergamaschi L, et al. Echocardiographic markers in the diagnosis of cardiac masses. J Am Soc Echocardiogr. 2023;36(5):464-473.e2.CrossRefPubMed
13.
go back to reference D’Angelo EC, Paolisso P, Vitale G, et al. Diagnostic accuracy of cardiac computed tomography and 18-F fluorodeoxyglucose positron emission tomography in cardiac masses. JACC Cardiovasc Imaging. 2020;13:2400–11.CrossRefPubMed D’Angelo EC, Paolisso P, Vitale G, et al. Diagnostic accuracy of cardiac computed tomography and 18-F fluorodeoxyglucose positron emission tomography in cardiac masses. JACC Cardiovasc Imaging. 2020;13:2400–11.CrossRefPubMed
14.
go back to reference Bedetti G, Pasanisi EM, Pizzi C, Turchetti G, Loré C. Economic analysis including long-term risks and costs of alternative diagnostic strategies to evaluate patients with chest pain. Cardiovasc Ultrasound. 2008;6:21.CrossRefPubMedPubMedCentral Bedetti G, Pasanisi EM, Pizzi C, Turchetti G, Loré C. Economic analysis including long-term risks and costs of alternative diagnostic strategies to evaluate patients with chest pain. Cardiovasc Ultrasound. 2008;6:21.CrossRefPubMedPubMedCentral
15.
go back to reference Bedetti G, Pizzi C, Gavaruzzi G, Lugaresi F, Cicognani A, Picano E. Suboptimal awareness of radiologic dose among patients undergoing cardiac stress scintigraphy. J Am Coll Radiol. 2008;5:126–31.CrossRefPubMed Bedetti G, Pizzi C, Gavaruzzi G, Lugaresi F, Cicognani A, Picano E. Suboptimal awareness of radiologic dose among patients undergoing cardiac stress scintigraphy. J Am Coll Radiol. 2008;5:126–31.CrossRefPubMed
17.
go back to reference Lyon AR, López-Fernández T, Couch LS, et al. 2022 ESC guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur Heart J. 2022;43:4229–361.CrossRefPubMed Lyon AR, López-Fernández T, Couch LS, et al. 2022 ESC guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur Heart J. 2022;43:4229–361.CrossRefPubMed
18.
go back to reference Zamorano JL, Lancellotti P, Rodriguez Muñoz D, et al. 2016 ESC position paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for practice guidelines: the task force for cancer treatments and cardiovascular toxicity of the European Society of Cardiology (ESC). Eur Heart J. 2016;37:2768–801.CrossRefPubMed Zamorano JL, Lancellotti P, Rodriguez Muñoz D, et al. 2016 ESC position paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for practice guidelines: the task force for cancer treatments and cardiovascular toxicity of the European Society of Cardiology (ESC). Eur Heart J. 2016;37:2768–801.CrossRefPubMed
19.
go back to reference Fitzpatrick T, Carrier M, Le Gal G. Cancer, atrial fibrillation, and stroke. Thromb Res. 2017;155:101–5.CrossRefPubMed Fitzpatrick T, Carrier M, Le Gal G. Cancer, atrial fibrillation, and stroke. Thromb Res. 2017;155:101–5.CrossRefPubMed
20.
go back to reference Russo V, Rago A, Papa A, 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;44:370–6.CrossRefPubMed Russo V, Rago A, Papa A, 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;44:370–6.CrossRefPubMed
21.
go back to reference Steffel J, Collins R, Antz M, et al. 2021 European Heart Rhythm Association practical guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. EP Eur. 2021;23:1612–76. Steffel J, Collins R, Antz M, et al. 2021 European Heart Rhythm Association practical guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. EP Eur. 2021;23:1612–76.
22.
go back to reference Hindricks G, Potpara T, Dagres N, et al. 2020 ESC guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2021;42:373–498.CrossRefPubMed Hindricks G, Potpara T, Dagres N, et al. 2020 ESC guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2021;42:373–498.CrossRefPubMed
23.
go back to reference Anon. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013;310(2):2191–4. Anon. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013;310(2):2191–4.
24.
go back to reference McLean E, Cogswell M, Egli I, Wojdyla D, de Benoist B. Worldwide prevalence of anaemia, WHO vitamin and mineral nutrition information system, 1993–2005. Public Health Nutr. 2009;12:444.CrossRefPubMed McLean E, Cogswell M, Egli I, Wojdyla D, de Benoist B. Worldwide prevalence of anaemia, WHO vitamin and mineral nutrition information system, 1993–2005. Public Health Nutr. 2009;12:444.CrossRefPubMed
25.
go back to reference Prins MH, Lensing AWA, Brighton TA, et al. Oral rivaroxaban versus enoxaparin with vitamin K antagonist for the treatment of symptomatic venous thromboembolism in patients with cancer (EINSTEIN-DVT and EINSTEIN-PE): a pooled subgroup analysis of two randomised controlled trials. Lancet Haematol. 2014;1:e37–46.CrossRefPubMed Prins MH, Lensing AWA, Brighton TA, et al. Oral rivaroxaban versus enoxaparin with vitamin K antagonist for the treatment of symptomatic venous thromboembolism in patients with cancer (EINSTEIN-DVT and EINSTEIN-PE): a pooled subgroup analysis of two randomised controlled trials. Lancet Haematol. 2014;1:e37–46.CrossRefPubMed
26.
go back to reference Agnelli G, Buller HR, Cohen A, et al. Oral apixaban for the treatment of venous thromboembolism in cancer patients: results from the AMPLIFY trial. J Thromb Haemost. 2015;13:2187–91.CrossRefPubMed Agnelli G, Buller HR, Cohen A, et al. Oral apixaban for the treatment of venous thromboembolism in cancer patients: results from the AMPLIFY trial. J Thromb Haemost. 2015;13:2187–91.CrossRefPubMed
27.
go back to reference Sacco RL, Kasner SE, Broderick JP, et al. An updated definition of stroke for the 21st century: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2013;44:2064–89.CrossRefPubMedPubMedCentral Sacco RL, Kasner SE, Broderick JP, et al. An updated definition of stroke for the 21st century: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2013;44:2064–89.CrossRefPubMedPubMedCentral
28.
go back to reference Thygesen K, Alpert JS, Jaffe AS, et al. Fourth universal definition of myocardial infarction (2018). Eur Heart J. 2019;40:237–69.CrossRefPubMed Thygesen K, Alpert JS, Jaffe AS, et al. Fourth universal definition of myocardial infarction (2018). Eur Heart J. 2019;40:237–69.CrossRefPubMed
29.
go back to reference 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;3:692–4.CrossRefPubMed 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;3:692–4.CrossRefPubMed
30.
go back to reference Hu Y-F, Chen Y-J, Lin Y-J, Chen S-A. Inflammation and the pathogenesis of atrial fibrillation. Nat Rev Cardiol. 2015;12:230–43.CrossRefPubMed Hu Y-F, Chen Y-J, Lin Y-J, Chen S-A. Inflammation and the pathogenesis of atrial fibrillation. Nat Rev Cardiol. 2015;12:230–43.CrossRefPubMed
31.
go back to reference Mery B, Guichard J-B, Guy J-B, et al. Atrial fibrillation in cancer patients: hindsight, insight and foresight. Int J Cardiol. 2017;240:196–202.CrossRefPubMed Mery B, Guichard J-B, Guy J-B, et al. Atrial fibrillation in cancer patients: hindsight, insight and foresight. Int J Cardiol. 2017;240:196–202.CrossRefPubMed
32.
go back to reference D’Souza M, Carlson N, Fosbøl E, et al. CHA2 DS2-VASc score and risk of thromboembolism and bleeding in patients with atrial fibrillation and recent cancer. Eur J Prev Cardiol. 2018;25:651–8.CrossRefPubMed D’Souza M, Carlson N, Fosbøl E, et al. CHA2 DS2-VASc score and risk of thromboembolism and bleeding in patients with atrial fibrillation and recent cancer. Eur J Prev Cardiol. 2018;25:651–8.CrossRefPubMed
33.
go back to reference 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;120:213–7.CrossRefPubMedPubMedCentral 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;120:213–7.CrossRefPubMedPubMedCentral
34.
go back to reference 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: e008987.CrossRefPubMedPubMedCentral 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: e008987.CrossRefPubMedPubMedCentral
35.
go back to reference 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;130:1440-1448.e1.CrossRefPubMed 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;130:1440-1448.e1.CrossRefPubMed
36.
go back to reference Pardo Sanz A, Rincón LM, Guedes Ramallo P, et al. Current status of anticoagulation in patients with breast cancer and atrial fibrillation. Breast. 2019;46:163–9.CrossRefPubMed Pardo Sanz A, Rincón LM, Guedes Ramallo P, et al. Current status of anticoagulation in patients with breast cancer and atrial fibrillation. Breast. 2019;46:163–9.CrossRefPubMed
37.
go back to reference Pritchard ER, Murillo JR, Putney D, Hobaugh EC. Single-center, retrospective evaluation of safety and efficacy of direct oral anticoagulants versus low-molecular-weight heparin and vitamin K antagonist in patients with cancer. J Oncol Pharm Pract. 2019;25:52–9.CrossRefPubMed Pritchard ER, Murillo JR, Putney D, Hobaugh EC. Single-center, retrospective evaluation of safety and efficacy of direct oral anticoagulants versus low-molecular-weight heparin and vitamin K antagonist in patients with cancer. J Oncol Pharm Pract. 2019;25:52–9.CrossRefPubMed
38.
go back to reference Angelini DE, Radivoyevitch T, McCrae KR, Khorana AA. Bleeding incidence and risk factors among cancer patients treated with anticoagulation. Am J Hematol. 2019;94(7):780–5.CrossRefPubMed Angelini DE, Radivoyevitch T, McCrae KR, Khorana AA. Bleeding incidence and risk factors among cancer patients treated with anticoagulation. Am J Hematol. 2019;94(7):780–5.CrossRefPubMed
39.
go back to reference Johnstone C, Rich SE. Bleeding in cancer patients and its treatment: a review. Ann Palliat Med. 2018;7:265–73.CrossRefPubMed Johnstone C, Rich SE. Bleeding in cancer patients and its treatment: a review. Ann Palliat Med. 2018;7:265–73.CrossRefPubMed
40.
go back to reference Gage BF, Yan Y, Milligan PE, et al. Clinical classification schemes for predicting hemorrhage: results from the National Registry of Atrial Fibrillation (NRAF). Am Heart J. 2006;151:713–9.CrossRefPubMed Gage BF, Yan Y, Milligan PE, et al. Clinical classification schemes for predicting hemorrhage: results from the National Registry of Atrial Fibrillation (NRAF). Am Heart J. 2006;151:713–9.CrossRefPubMed
Metadata
Title
Impact of Newly Diagnosed Cancer on Bleeding Events in Patients with Atrial Fibrillation Treated with Direct Oral Anticoagulants
Authors
Francesco Angeli
Luca Bergamaschi
Matteo Armillotta
Angelo Sansonetti
Andrea Stefanizzi
Lisa Canton
Francesca Bodega
Nicole Suma
Sara Amicone
Damiano Fedele
Davide Bertolini
Andrea Impellizzeri
Francesco Pio Tattilo
Daniele Cavallo
Lorenzo Bartoli
Ornella Di Iuorio
Khrystyna Ryabenko
Marcello Casuso Alvarez
Virginia Marinelli
Claudio Asta
Mariachiara Ciarlantini
Giuseppe Pastore
Andrea Rinaldi
Daniela Paola Pomata
Ilaria Caldarera
Carmine Pizzi
Publication date
06-09-2024
Publisher
Springer International Publishing
Published in
American Journal of Cardiovascular Drugs
Print ISSN: 1175-3277
Electronic ISSN: 1179-187X
DOI
https://doi.org/10.1007/s40256-024-00676-y

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