Atrial Fibrillation
Anticoagulation for Atrial Fibrillation in Patients With Cancer
2022 Volume 86 Issue 2 Pages 211-212
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2022 Volume 86 Issue 2 Pages 211-212
Cancer is an independent risk factor for atrial fibrillation (AF). A population-based study in Korea reported a 1.6-fold increase in incident AF in patients with cancer compared with age- and sex-matched controls without cancer.1 There are several putative explanations for the increased risk of AF in patients with cancer.2 Cancer-related systemic inflammation is thought to contribute to atrial remodeling. Autonomic nervous system imbalance due to pain and emotional and/or physical stress may also predispose to AF. Moreover, AF may be a complication of cancer therapies, including surgery and chemotherapy. With the aging of society, the prevalence of AF in patients with cancer is expected to increase, but there is insufficient data on the effect of active cancer on outcomes in elderly patients with AF.
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Patients with cancer simultaneously have hypercoagulability and bleeding diathesis. In addition, they have a 4- to 7-fold higher risk of venous thromboembolism (VTE) than the general population or patients without cancer, as well as a 2-fold higher risk of bleeding during anticoagulation therapy.3 The efficacy and safety of anticoagulation in patients with cancer remain topics of interest. Previously, we reported that direct oral anticoagulants (DOACs) are as effective as warfarin in preventing stroke and systemic embolism without increasing the risk of major bleeding among Japanese patients with cancer with AF.4 However, that was a single-center retrospective study with a small sample size. Further investigation is warranted to confirm the efficacy and safety of oral anticoagulants in patients with AF and cancer.
In this issue of the Journal, Ikeda et al5 report their findings from a study that prospectively evaluated the effect of active cancer on thrombosis and bleeding risk in elderly patients with AF using real-world data. There was no significant difference in the incident rate of stroke/systemic embolic events (SEE) between elderly patients with AF and active cancer, and those without active cancer. Patients with active cancer had a higher incidence of major bleeding and all-cause death than those without active cancer. No differences in efficacy and safety were observed between DOACs and warfarin in elderly patients with AF and cancer. Thus, Ikeda et al provide new insights into the effect of active cancer on outcomes in elderly patients with AF.
It is interesting to note that the incidence of stroke/SEE in the cancer group was similar to that in the non-cancer group (hazard ratio [HR], 1.00; 95% confidence interval [CI], 0.82–1.22).5 Because hypercoagulability has been reported to be associated with the increased risk of VTE in patients with cancer,6 it can be assumed that cancer-related hypercoagulability could exacerbate thrombus formation in patients with AF. However, post-hoc analyses of several randomized clinical trials showed similar incidences of thromboembolic events. The ROCKET AF trial showed no difference in the incidence of stroke/SEE (HR, 0.86; 95% CI, 0.55–1.33) in patients with a history of cancer compared with patients without a history of cancer.7 In the ARISTOTLE trial, there was no significant difference in the incidence of stroke/SEE between patients with cancer (12.7% with active cancer, and 87.3% with remote cancer) and those without cancer (HR, 0.93; 95% CI, 0.63–1.37).8 The ENGAGE AF-TIMI 48 trial showed that active cancer was not associated with an increased risk of stroke/SEE (HR, 1.08; 95% CI, 0.83–1.42).9 The present study revealed that active cancer had a similar effect on the incidence of stroke/SEE in elderly patients with AF.
The risk of bleeding in patients with AF and cancer may be associated with cancer status (active cancer, remote cancer, or history of cancer). In the present study, Ikeda et al report that elderly patients with active cancer and AF were at a higher risk of major bleeding.5 Their result is consistent with the findings of the ENGAGE AF-TIMI 48 trial.9 On the other hand, the ROCKET AF trial showed no significant difference in major bleeding (HR, 1.17; 95% CI, 0.88–1.54) between patients with and those without a history of cancer.7 In the ARISTOTLE trial, there was no significant difference in any bleeding between patients with cancer (12.7% with active cancer, and 87.3% with remote cancer) and those without cancer (HR, 1.10; 95% CI, 0.99–1.22).8
It is necessary to pay attention to drug interactions during anticoagulation in patients with cancer. DOACs are substrates of the permeability glycoprotein (P-gp) or cytochrome P450 (CYP3A4), which are induced or inhibited by some chemotherapeutic agents.10 Warfarin also interacts with other drugs (e.g., 5-fluorouracil and capecitabine).11,12 In addition, appetite loss due to cancer itself and/or chemotherapy can affect the international normalized ratio. Therefore, the use of warfarin in patients with cancer is challenging. In the present study, there were no differences in efficacy and safety between DOACs and warfarin in elderly patients with AF and cancer.5 It is conceivable that DOACs could be an available alternative to warfarin in elderly patients with AF and cancer.
Some aspects of the management of patients with AF and cancer, such as the effect of cancer status, stage, type, and treatment on thrombosis and risk of bleeding in patients with AF, need to be addressed in future studies. Several risk assessment scores, such as the CHADS2, CHA2DS2-VASc, and HAS-BLED scores, do not include cancer as a risk factor in patients with AF. The usefulness of these scores in patients with cancer remains to be clarified. Despite these limitations, the present study provides new and important information on the effect of active cancer on outcomes in elderly Japanese patients with AF.
The authors declare there are no conflicts of interest and no funding.
