Risk of arterial thromboembolism in patients with concomitant atrial fibrillation and cancer: a systematic review and meta-analysis
Authors: Balomenakis C , Papazoglou A , Vlachopoulou D , Kartas A , Moysidis D , Vouloagkas I , Tsagkaris C , Samaras A , Krystalli C , Karagiannidis E , Giannakoulas G 
Published: October 2022

Abstract

Background/Introduction
Atrial fibrillation (AF) and cancer often co-exist and have been independently associated with increased risk of arterial thromboembolism (TE), all cause death and bleeding; however, no cumulative data exist regarding the clinical course of AF patients with comorbid cancer.

Purpose
The aim of this systematic review and meta-analysis is to synthesize the available data regarding the incidence of major adverse cardiovascular events in AF patients in association with concurrent cancer.

Methods
The composite outcome of any TE (ischemic stroke, transient ischemic attack, or arterial thrombosis) was defined as the primary study outcome, while all-cause mortality and major or clinically relevant non-major bleeding occurrence as the secondary ones. Literature search was conducted in PubMed (MEDLINE), WebOfScience, Scopus, CENTRAL, OpenGrey, and EThOS databases. A random-effects model meta-analysis was performed. Subgroup analyses were conducted assessing the effect of active cancer history and various cancer subtypes on the outcomes of interest. Meta-regression analyses were also performed to examine the relative impact of CHA2DS2VASC and HASBLED prognostic scores on the risk of TE and bleeding, respectively.

Results
Overall 17 studies were included in our analysis, encompassing a total of 3,151,861 AF patients. Comorbid cancer was non-significantly associated with lower odds of TE than AF alone (pooled odds ratio (pOR) = 0.85, 95% confidence interval (CI): 0.69–1.03, I2=87%). The likelihood for all-cause death and bleeding occurrence was significantly higher in AF patients with cancer (pOR = 2.27, 95% CI: 1.69–3.06, I2=99%); pOR = 1.58, 95% CI: 1.26–1.97, I2=97% respectively) compared to those without cancer. Subgroup analysis on active cancer status did not yield any substantial difference, marginally improving the heterogeneity of our analysis. The highest all-cause mortality likelihood was observed in Liver-Pancreas-Gallbladder category (pOR = 10.58, 95% CI: 4.69–23.88, I2=98%) while the highest bleeding likelihood was encountered in Genitourinary cancer (pOR = 1.90, 95% CI: 1.42–2.55, I2=71.9%). The performed meta-regression analyses did not yield any significant results.

Conclusions
Our meta-analysis of 17 eligible studies demonstrated that cancer does not seem to be associated with increased risk of TE, while with increased all-cause death and bleeding occurrence in AF patients. This correlation might be explained by higher cancer-driven mortality rates (competing risk), many cases of TE being left undiagnosed within the scope of palliative cancer care, misdiagnosed episodes of TE due to the presence of brain metastases, optimal cardio-oncology monitoring, and more frequent usage of prophylactic anticoagulation treatment for cancer-associated venous thromboembolism. Nonetheless, further competing-risk survival analyses are warranted before reaching definite conclusions.

Funding Acknowledgement
Type of funding sources: None.