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. 2025 Feb;7(2):157-167.
doi: 10.1016/j.jaccao.2024.10.014. Epub 2025 Jan 14.

The Association of Malignancy With Stroke and Bleeding in Atrial Fibrillation: A Population-Based Cohort Study

Malak El-Rayes  1 , Mohamed Adam  2 , Jiming Fang  3 , Xuesong Wang  3 , Irene Jeong  3 , Peter C Austin  4 , Andrew C T Ha  5 , Michael G Fradley  6 , Thomas A Boyle  6 , Eitan Amir  7 , Paaladinesh Thavendiranathan  8 , Husam Abdel-Qadir  9
Affiliations

The Association of Malignancy With Stroke and Bleeding in Atrial Fibrillation: A Population-Based Cohort Study

Malak El-Rayes et al. JACC CardioOncol. 2025 Feb.

Abstract

Background: It is undetermined if malignancy independently increases stroke risk in atrial fibrillation (AF).

Objectives: This study sought to determine the association of malignancy with stroke and bleeding in AF.

Methods: Population-based cohort study using administrative datasets of people aged ≥66 years with newly diagnosed AF. People diagnosed with malignancy within 5 years before AF diagnosis were matched to cancer-free control subjects on age, sex, AF diagnosis details, CHA2DS2-VASc score, and ATRIA bleeding score. Outcomes included hospitalizations for stroke and hospitalization/emergency visits for bleeding. Cause-specific regression was used to determine the HR for malignancy after adjusting for time-varying anticoagulation status. Analyses were repeated for specific subgroups of cancer patients (with matched control subjects).

Results: Among 199,710 AF patients, 24,991 (12.5%) people had prior malignancy. Malignancy was associated with more inpatient diagnoses of AF (vs outpatient) and less anticoagulation. We matched 43,802 people with AF (21,901 with malignancy, mean age 78.1 years; 59.5% male). After adjusting for anticoagulation status, malignancy had a similar hazard of stroke (HR: 1.01; 95% CI: 0.88-1.15) but higher hazard of bleeding (HR: 1.45; 95% CI: 1.37-1.53) compared with cancer-free control subjects in the matched sample. Analyses of cancer subgroups with comparison to matched control subjects mostly showed consistent results, except for: 1) increased hazard of stroke in lung cancer; and 2) lack of increased bleeding hazard in breast cancer and lymphoma.

Conclusions: People with AF and malignancy generally had similar hazards of stroke but higher hazards of bleeding compared with cancer-free control subjects, suggesting that malignancy should not lower the threshold for anticoagulation in AF.

Keywords: ATRIA; CHA(2)DS(2)-VASc score; anticoagulation; arrhythmia; atrial fibrillation; bleeding; cancer; cerebrovascular disease; epidemiology; stroke; thrombosis.

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Conflict of interest statement

Funding Support and Author Disclosures This study was funded by the Canadian Cardiovascular Society Atrial Fibrillation Research Award and the Ted Rogers Program in Cardiotoxicity Prevention. Dr Adam was funded by the Heart & Stroke/Richard Lewar Centre of Excellence in Cardiovascular Research. Dr Abdel-Qadir was supported by a National New Investigator Award from the Heart and Stroke Foundation of Canada. Dr Thavendiranathan was supported by a Tier II Canada Research Chair and the Canadian Cancer Society/Canadian Institutes of Health Research’s W. David Hargraft Grant (no. 706710). This study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health and the Ministry of Long-Term Care. This study also received funding from the sources described previously. The analyses, conclusions, opinions and statements expressed herein are solely those of the authors and do not reflect those of the funding or data sources; no endorsement is intended or should be inferred. Dr Abdel-Qadir has received consulting and speaker honoraria from Amgen, AstraZeneca, and Jazz Pharmaceuticals. Dr Amir has received honoraria from Seagen, Gilead, Pfizer, and Novartis; and served as a consultant or advisor for AstraZeneca and Novartis. Dr Ha has received speaker honoraria from Bayer, BMS/Pfizer Alliance, and Servier. Dr Thavendiranathan has received consulting and speaker honoraria from GE, Amgen, Boehringer Ingelheim, and AstraZeneca. Dr Fradley has received research grants from Medtronic and AstraZeneca; and consulting fees from AstraZeneca, AbbVie, Janssen, Johnson and Johnson, Pfizer, and Zoll. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Figures

None
Graphical abstract
Figure 1
Figure 1
HR and 95% CI for Stroke Associated With CHA2DS2-VA Scores The HR for stroke associated with different CHA2DS2-VA scores (relative to a score of 1) in people with atrial fibrillation and cancer (left) and cancer-free people with atrial fibrillation (right).
Figure 2
Figure 2
HR and 95% CI for Stroke in Atrial Fibrillation Associated With Cancer The cause-specific HR for stroke associated with a history of malignancy in people with atrial fibrillation relative to cancer-free control subjects, after matching on key risk factors and adjusting for time-varying anticoagulation status. We present data for the full cohort, followed by subgroups of patients with malignancy in comparison with their matched control subjects.
Figure 3
Figure 3
HR and 95% CI for Bleeding in Atrial Fibrillation Associated With Cancer The cause-specific HR for bleeding associated with a history of malignancy in people with atrial fibrillation relative to cancer-free control subjects, after matching on key risk factors and adjusting for time-varying anticoagulation status. We present data for the full cohort, followed by subgroups of patients with malignancy in comparison with their matched control subjects.
Central Illustration
Central Illustration
The Association of Malignancy With Stroke and Bleeding in AF Atrial fibrillation (AF) is associated with lower rates of anticoagulation in patients with cancer compared with cancer-free control subjects. After accounting for differences between groups, cancer is not associated with differences in stroke risks, but some cancers are associated with higher bleeding risk. ATRIA = Anticoagulation and Risk Factors in Atrial Fibrillation.
See this image and copyright information in PMC

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