Management of atrial fibrillation in patients taking targeted cancer therapies

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Abstract

Atrial fibrillation (AF) is frequently observed in patients being treated for cancer and can lead to increased morbidity and mortality in this population. With the use of newer, targeted cancer therapies, several drug-drug interactions have emerged that complicate the use of antiarrhythmic drugs (AADs) in patients with active malignancy. Moreover, specific targeted therapies such as ibrutinib may contribute directly to the development of AF. The decision to pursue systemic anticoagulation can be challenging in patients with malignancy due to a number of factors, including the need for frequent procedures, the presence of malignancy-related risk factors for bleeding, and limited data regarding the safety of the novel oral anticoagulants (NOACs) in cancer patients. This review describes the challenges associated with AF management in patients with cancer and highlights a number of important drug-drug interactions that can impact patient management.

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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.

A S Go, E Hylek, K. Phillips … (2001)

Atrial fibrillation is the most common arrhythmia in elderly persons and a potent risk factor for stroke. However, recent prevalence and projected future numbers of persons with atrial fibrillation are not well described. To estimate prevalence of atrial fibrillation and US national projections of the numbers of persons with atrial fibrillation through the year 2050. Cross-sectional study of adults aged 20 years or older who were enrolled in a large health maintenance organization in California and who had atrial fibrillation diagnosed between July 1, 1996, and December 31, 1997. Prevalence of atrial fibrillation in the study population of 1.89 million; projected number of persons in the United States with atrial fibrillation between 1995-2050. A total of 17 974 adults with diagnosed atrial fibrillation were identified during the study period; 45% were aged 75 years or older. The prevalence of atrial fibrillation was 0.95% (95% confidence interval, 0.94%-0.96%). Atrial fibrillation was more common in men than in women (1.1% vs 0.8%; P<.001). Prevalence increased from 0.1% among adults younger than 55 years to 9.0% in persons aged 80 years or older. Among persons aged 50 years or older, prevalence of atrial fibrillation was higher in whites than in blacks (2.2% vs 1.5%; P<.001). We estimate approximately 2.3 million US adults currently have atrial fibrillation. We project that this will increase to more than 5.6 million (lower bound, 5.0; upper bound, 6.3) by the year 2050, with more than 50% of affected individuals aged 80 years or older. Our study confirms that atrial fibrillation is common among older adults and provides a contemporary basis for estimates of prevalence in the United States. The number of patients with atrial fibrillation is likely to increase 2.5-fold during the next 50 years, reflecting the growing proportion of elderly individuals. Coordinated efforts are needed to face the increasing challenge of optimal stroke prevention and rhythm management in patients with atrial fibrillation.

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Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer.

Agnes Lee, Mark N Levine, Ross Baker … (2003)

Patients with cancer have a substantial risk of recurrent thrombosis despite the use of oral anticoagulant therapy. We compared the efficacy of a low-molecular-weight heparin with that of an oral anticoagulant agent in preventing recurrent thrombosis in patients with cancer. Patients with cancer who had acute, symptomatic proximal deep-vein thrombosis, pulmonary embolism, or both were randomly assigned to receive low-molecular-weight heparin (dalteparin) at a dose of 200 IU per kilogram of body weight subcutaneously once daily for five to seven days and a coumarin derivative for six months (target international normalized ratio, 2.5) or dalteparin alone for six months (200 IU per kilogram once daily for one month, followed by a daily dose of approximately 150 IU per kilogram for five months). During the six-month study period, 27 of 336 patients in the dalteparin group had recurrent venous thromboembolism, as compared with 53 of 336 patients in the oral-anticoagulant group (hazard ratio, 0.48; P=0.002). The probability of recurrent thromboembolism at six months was 17 percent in the oral-anticoagulant group and 9 percent in the dalteparin group. No significant difference between the dalteparin group and the oral-anticoagulant group was detected in the rate of major bleeding (6 percent and 4 percent, respectively) or any bleeding (14 percent and 19 percent, respectively). The mortality rate at six months was 39 percent in the dalteparin group and 41 percent in the oral-anticoagulant group. In patients with cancer and acute venous thromboembolism, dalteparin was more effective than an oral anticoagulant in reducing the risk of recurrent thromboembolism without increasing the risk of bleeding. Copyright 2003 Massachusetts Medical Society

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Acalabrutinib (ACP-196) in Relapsed Chronic Lymphocytic Leukemia.

John C. Byrd, Bonnie Harrington, Susan O’Brien … (2016)

Irreversible inhibition of Bruton's tyrosine kinase (BTK) by ibrutinib represents an important therapeutic advance for the treatment of chronic lymphocytic leukemia (CLL). However, ibrutinib also irreversibly inhibits alternative kinase targets, which potentially compromises its therapeutic index. Acalabrutinib (ACP-196) is a more selective, irreversible BTK inhibitor that is specifically designed to improve on the safety and efficacy of first-generation BTK inhibitors.

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Contributors

Aarti Asnani: aasnani@mgh.harvard.edu

Anastasia Manning: Anastasia_MM@outlook.com

Moussa Mansour: mmansour@mgh.harvard.edu

Jeremy Ruskin: jruskin@mgh.harvard.edu

Ephraim P. Hochberg: ehochberg@mgh.harvard.edu

Leon M. Ptaszek: lptaszek@mgh.harvard.edu

Journal

Journal ID (nlm-ta): Cardiooncology

Journal ID (iso-abbrev): Cardiooncology

Title: Cardio-oncology

Publisher: BioMed Central (London )

ISSN (Electronic): 2057-3804

Publication date (Electronic): 9 March 2017

Publication date PMC-release: 9 March 2017

Publication date Collection: 2017

Volume: 3

Electronic Location Identifier: 2

Affiliations

[1 ]ISNI 0000 0004 0386 9924, GRID grid.32224.35, Cardio-Oncology Program, Corrigan Minehan Heart Center, Massachusetts General Hospital, ; 149 13th Street, Room 4.302, Boston, MA 02129 USA

[2 ]ISNI 0000 0004 0386 9924, GRID grid.32224.35, Massachusetts General Hospital, ; Boston, MA 02129 USA

[3 ]ISNI 0000 0004 0386 9924, GRID grid.32224.35, Cardiac Arrhythmia Service, Corrigan-Minehan Heart Center, , Massachusetts General Hospital, ; 55 Fruit Street, GRB 109, Boston, MA 02114 USA

[4 ]ISNI 0000 0004 0386 9924, GRID grid.32224.35, Hematology/Oncology, Cancer Center, , Massachusetts General Hospital, ; 55 Fruit Street, Boston, MA 02114 USA

Article

Publisher ID: 21

DOI: 10.1186/s40959-017-0021-y

PMC ID: 7048041

PubMed ID: 32153998

SO-VID: 8afff278-4a30-4921-bfb7-b0eb053294be

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Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 9 November 2016

Date accepted : 18 January 2017

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Keywords: atrial fibrillation,cancer,chemotherapy,targed therapies,ibrutinib,anticoagulation

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Keywords: atrial fibrillation, cancer, chemotherapy, targed therapies, ibrutinib, anticoagulation

Management of atrial fibrillation in patients taking targeted cancer therapies

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Most cited references 23

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.

Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer.

Acalabrutinib (ACP-196) in Relapsed Chronic Lymphocytic Leukemia.

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