Atrial fibrillation (AF) is common in patients with cancer, and up to one in every four persons with AF has comorbid cancer [1,2].
AF in cancer patients increases the risk of adverse cardiovascular events, further increasing the risk of venous thromboembolism and major bleeding (especially after the beginning of anticoagulation therapy) .
This risk combination complicates the treatment of AF in cancer patients. Therefore, in the absence of a high risk of bleeding, anticoagulation is recommended to prevent stroke in AF patients with CHA2DS2-VASc scores ≥2 in males or ≥3 in females .
CHA2DS2-VASc is the risk score used to identify patients with high arterial thromboembolism (ATE) risk that need anticoagulation treatment. Unfortunately, the CHA2DS2-VASC score does not consider the presence of malignancy, and no reliable VTE risk scores are available for people with cancer and AF .
Considering this, understanding the risk of ATE in patients with cancer and AF is of utmost importance for choosing the best therapeutic approach.
A recent population-based retrospective cohort study assessed if AF patients with CHA2DS2-VASc scores of 0–2 and newly diagnosed cancer (not receiving anticoagulation) have an increased risk of ATE .
The study excluded subjects receiving anticoagulation at the study index and having ATE or possible cancer at any time before the study index.
Subjects were divided into four cohorts: two experimental cohorts, including patients with AF and cancer (‘AF and cancer’, 1411 subjects) or with AF and without cancer (‘AF and no cancer’, 4233 subjects), and two control cohorts, including patients without AF but with cancer (‘no AF and cancer’, 4233 subjects) or without AF and cancer (‘no AF and no cancer’, 19421 subjects) .
In all cohorts, AF was diagnosed previously study index using International Classification of Diseases-Ninth Revision (ICD-9) codes. Subjects were indexed on the date of cancer diagnosis for the ‘AF and cancer’ and the ‘no AF and cancer’ cohorts and on the matched date for the ‘AF and no cancer’ and the ‘no AF and no cancer’ cohorts.
AF, cancer, and ATE
The study results indicate that AF patients with CHA2DS2-VASc ≤2 not receiving anticoagulation at the time of cancer diagnosis have an associated 2.7-fold increase in ATE incidence over the first 12 months compared with matched controls without cancer.
AF patients with cancer had an absolute 12-month cumulative incidence of ATE of 2.13%, while for the matched AF patients without was 0.8%.
These results might indicate that the CHA2DS2-VASc score underestimates the risk of ATE in patients with AF and newly diagnosed cancer.
Also, a subgroup analysis indicates that the risk of ATE over the first 12 months is increased in AF patients with cancer and intermediate thrombotic risk (men with CHA2DS2-VASc = 1 and women with CHA2DS2-VASc = 2) compared with patients without cancer.
Of note, the risk was not increased among men with CHA2DS2-VASc = 2, who are strongly recommended for anticoagulation.
This might indicate that ATE risk can especially increase in patients with cancer without a strong recommendation for anticoagulation according to current guidelines.
AF, cancer, and bleeding
As expected, the cancer cohorts had a higher 12-month incidence of bleeding than the respective noncancer cohorts, regardless of the presence of AF, confirming the higher risk of bleeding in cancer patients. Specifically, the risk of a first bleeding event during the first 12 months was higher in the ‘AF and cancer’ cohort than in the ‘AF and no cancer’ cohort (HR: 2.79; 95% CI: 1.39–5.58) and in the ‘no AF and cancer’ cohort than in the ‘no AF and no cancer’ cohort (HR: 5.62; 95% CI: 3.97–7.95).
In this study, patients were matched for CHA2DS2-VASc scores, age, sex, index year, and duration of AF, but an imbalance in ATE risk factors between the cohorts cannot be ruled out.
Also, there are differences in cardiovascular risk factors between the AF and non-AF populations: the AF population contained more hypertension, heart failure, vascular disease, ischemic heart disease, and diabetes cases.
Finally, no data were available on cancer stage and anticancer treatment, which can modify the risk of thrombosis in patients with cancer.
In AF patients with CHA2DS2-VASc scores of 0–2, newly diagnosed cancer is associated with an increased incidence of stroke, transient ischemic attack, or systemic ATE compared with matched controls without cancer.
Patients with newly diagnosed cancer, AF, and CHA2DS2-VASc scores ≤2 not receiving anticoagulation at cancer diagnosis are associated with an increased ATE incidence over the first 12 months compared with matched controls without cancer.
The risk peaks in men with CHA2DS2-VASc = 1 and women with CHA2DS2-VASc = 2.
- Farmakis D, Parissis J, Filippatos G. Insights into onco-cardiology: atrial fibrillation in cancer. J Am Coll Cardiol. 2014;63(10):945-953.
- Melloni C, Shrader P, Carver J, et al. Management and outcomes of patients with atrial fibrillation and a history of cancer: the ORBIT-AF registry. Eur Heart J Qual Care Clin Outcomes. 2017;3(3):192-197.
- Hu YF, Liu CJ, Chang PM, et al. Incident thromboembolism and heart failure associated with new-onset atrial fibrillation in cancer patients. Int J Cardiol. 2013;165(2):355-357.
- Leader A, Mendelson Cohen N, Afek S, et al. Arterial thromboembolism in patients with atrial fibrillation and CHA2DS2-VASc Score 0 to 2 with and without cancer. J Am Coll Cardiol CardioOnc. 2023 .https://doi.org/10.1016/j.jaccao.2022.08.014 (Epub ahead of press).
- Chu G, Versteeg HH, Verschoor AJ, et al. Atrial fibrillation and cancer – An unexplored field in cardiovascular oncology. Blood Rev. 2019;35:59-67.