Bleeding and New Malignancy Diagnoses After Anticoagulation for Atrial Fibrillation: A Population-Based Cohort Study.

IF 35.5 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS
Circulation Pub Date : 2025-03-18 Epub Date: 2025-02-20 DOI:10.1161/CIRCULATIONAHA.124.070865
Kavi Grewal, Xuesong Wang, Peter C Austin, Cynthia A Jackevicius, Inbar Nardi-Agmon, Dennis T Ko, Douglas S Lee, Paaladinesh Thavendiranathan, Michael Fradley, Paul Dorian, Husam Abdel-Qadir
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引用次数: 0

Abstract

Background: Bleeding after starting anticoagulation for atrial fibrillation (AF) may be the first sign of malignancy, especially in elderly individuals. There are no recommendations to guide investigations for malignancy after new-onset bleeding after anticoagulation for AF. Our objective was to determine the association of bleeding after starting oral anticoagulation for AF with new diagnoses of malignancy in a population-wide sample.

Methods: We conducted a population-based cohort study using linked administrative data sets of people ≥66 years of age who newly initiated warfarin or direct oral anticoagulants after diagnosis with AF between 2008 and 2022. Follow-up was 2 years after starting anticoagulation. We excluded patients with valvular disease, chronic dialysis, venous thromboembolism, previous cancer, or previously documented bleeding. Bleeding was identified from hospital/emergency department discharge records and physician billings, then handled as a time-varying covariate in cause-specific regression models while adjusting for baseline characteristics. The primary outcome was incident malignancy. We also determined the site of origin of the malignancy and the stage at diagnosis if indicated in the Ontario Cancer Registry. Analyses were repeated while limiting the exposure to specific bleeding sites.

Results: Among 119 480 people (mean age, 77.4 years; 52% men) who started anticoagulants, 26 037 (21.8%) had documented bleeding, and 5800 (4.9%) were diagnosed with malignancy within the next 2 years. Bleeding was associated with a higher hazard of cancer diagnosis with a hazard ratio (HR) of 4.0 (95% CI, 3.8-4.3). The HRs for any malignancy were 5.0 (95% CI, 4.6-5.5) for gastrointestinal, 5.0 (95% CI, 4.4-5.7) for genitourinary, 4.0 (95% CI, 3.5-4.6) for respiratory, 1.8 (95% CI, 1.4-2.2) for intracranial, and 1.5 (95% CI, 1.2-2.0) for nasopharyngeal bleeds. The HRs were substantially higher for cancers concordant with the bleeding site (gastrointestinal, 15.4; genitourinary, 11.8; respiratory, 10.1). Cancers were diagnosed at an earlier stage after bleeding (27.6% stage 4 after bleeding versus 31.3% without bleeding; P=0.029).

Conclusions: In anticoagulated patients with AF, bleeding was strongly associated with new cancer diagnoses. Antecedent bleeding was associated with cancer diagnosis at an earlier stage. This highlights the importance of timely investigations in patients with bleeding after anticoagulation for AF, rather than attributing bleeding as an expected adverse effect.

房颤抗凝后出血和新的恶性诊断:一项基于人群的队列研究。
背景:房颤(AF)开始抗凝治疗后出血可能是恶性肿瘤的第一个征兆,特别是在老年人中。对于房颤抗凝治疗后新发出血后的恶性肿瘤调查,目前尚无指导意见。我们的目的是在全人群样本中确定房颤口服抗凝治疗后出血与新诊断的恶性肿瘤之间的关系。方法:我们进行了一项基于人群的队列研究,使用了2008年至2022年间诊断为房颤后新开始使用华法林或直接口服抗凝剂的≥66岁患者的相关管理数据集。开始抗凝治疗后随访2年。我们排除了有瓣膜疾病、慢性透析、静脉血栓栓塞、既往癌症或既往记录出血的患者。从医院/急诊科的出院记录和医生账单中确定出血,然后在调整基线特征的同时,在病因特异性回归模型中作为时变协变量进行处理。主要结局为恶性肿瘤的发生。我们还确定了恶性肿瘤的起源地点和诊断阶段,如果在安大略省癌症登记处指出。在限制暴露于特定出血部位的同时重复分析。结果:119480例患者(平均年龄77.4岁;52%男性)开始使用抗凝剂,26037人(21.8%)有出血记录,5800人(4.9%)在接下来的2年内被诊断为恶性肿瘤。出血与较高的癌症诊断风险相关,风险比(HR)为4.0 (95% CI, 3.8-4.3)。胃肠道出血的hr为5.0 (95% CI, 4.6-5.5),泌尿生殖系统出血的hr为5.0 (95% CI, 4.4-5.7),呼吸系统出血的hr为4.0 (95% CI, 3.5-4.6),颅内出血的hr为1.8 (95% CI, 1.4-2.2),鼻咽出血的hr为1.5 (95% CI, 1.2-2.0)。伴有出血部位的癌症的hr要高得多(胃肠道,15.4;泌尿生殖器的11.8;呼吸,10.1)。癌症在出血后的早期阶段被诊断出来(27.6%在出血后的第4阶段,31.3%没有出血;P = 0.029)。结论:在抗凝治疗的房颤患者中,出血与新的癌症诊断密切相关。先前出血与早期癌症诊断相关。这突出了及时调查房颤抗凝后出血患者的重要性,而不是将出血归因于预期的不良反应。
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来源期刊
Circulation
Circulation 医学-外周血管病
CiteScore
45.70
自引率
2.10%
发文量
1473
审稿时长
2 months
期刊介绍: Circulation is a platform that publishes a diverse range of content related to cardiovascular health and disease. This includes original research manuscripts, review articles, and other contributions spanning observational studies, clinical trials, epidemiology, health services, outcomes studies, and advancements in basic and translational research. The journal serves as a vital resource for professionals and researchers in the field of cardiovascular health, providing a comprehensive platform for disseminating knowledge and fostering advancements in the understanding and management of cardiovascular issues.
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