Elsevier

Progress in Cardiovascular Diseases

Volume 66, May–June 2021, Pages 28-36
Progress in Cardiovascular Diseases

Review Article
Cancer and atrial fibrillation: Epidemiology, mechanisms, and anticoagulation treatment

https://doi.org/10.1016/j.pcad.2021.04.004Get rights and content

Abstract

Cancer patients are at an increased risk of developing atrial fibrillation (AF) and thrombosis. However, the management of anticoagulation in patients with both diseases may be challenging, and data on these patients are lacking. We summarize the current evidence on the incidence and prevalence of cancer in AF and vice versa and provide some practical considerations on the management of oral anticoagulation in specific clinical situations. Low-molecular weight heparins are not approved for thromboprophylaxis in AF, and management of warfarin can be difficult. The use of direct oral anticoagulants may be particularly attractive for their rapid onset/offset action and lower bleeding risk.

Introduction

Advances in screening techniques and treatments have improved the survival of patients with cancer, as shown by data from the American Cancer Society and National Cancer Institute reporting that more than 16.9 million Americans with a history of cancer were alive on January 1, 2019 and this number is expected to increase to 22.1 million by January 2030.1 However, an increased risk of developing cardiovascular diseases (CVD) compared with non–cancer controls is becoming evident in these patients.2 The most common CVD are heart failure (HF), coronary artery disease (CAD), valvular and pericardial diseases, venous thromboembolic disease, peripheral vascular diseases and pulmonary hypertension. In addition, there is a wide spectrum of rhythm disorders that may complicate the clinical course of cancer patients, ranging from brady-arrhythmias and conduction defects to supraventricular arrhythmias and atrial fibrillation (AF).3 The onset of AF may be promoted by the presence of cancer4, 5, 6, 7 and by cancer treatments such as surgery, chemotherapy (CT) and radiotherapy (RT).3,8,9 Furthermore, common risk factors may predispose to both cancer and AF, as well as there may be common pathways driving both tumorigenesis and AF development, such as inflammation.3,8,9

Current guidelines on the management of patients with AF and cancer do not provide clear-cut recommendations on the optimal thrombo-prophylaxis strategy in these patients, especially those undergoing CT or RT.

The purpose of this review is to summarize the current evidence on the relationship between AF and cancer and to provide some practical insights about the use of anticoagulants in this setting.

Section snippets

Risk of AF in patients with cancer

Several studies have shown a 20% prevalence of AF in patients with cancer,4, 5, 6, 7 regardless of the type of cancer.6,10 The highest risk of developing new AF was found in the first three months after the diagnosis of cancer,7 with the risk progressively decreasing after 6 months.10 This early detection of AF may be due to a tighter clinical monitoring of these patients after cancer diagnosis.

In one study, new onset AF was associated with a higher risk of thromboembolism [adjusted Hazard

Risk of cancer in patients with AF

Previous studies showed an increased risk of developing cancer in patients with AF. Indeed, the incidence of cancer in AF patients was reported to be 30–40% higher than in the general population, with men being more likely to develop cancer than women.43 In a retrospective study performed by Hung et al.,43 which included 332,555 AF patients (55.2% were men) without past history of cancer and with a mean age of 70.8 ± 13.1 years, of whom 68.5% were affected by hypertension, 28.4% by diabetes,

Mechanisms linking AF and cancer

There are several mechanisms potentially linking AF and cancer (Fig. 1), including systemic inflammation which seems to represent a common milieu for these two conditions. Increased production of chemokines and cytokines, such as interleukins 1 and 6, and systemic acute phase proteins such as C-reactive protein (CRP), has been described in patients with cancer.50 In addition, inflammation markers, such as high white blood cells, CRP and ceruloplasmin (HR 1.039, 95%CI 1.007–1.072, p = 0.016, HR

Ischaemic and bleeding risk in patients with AF and malignancies

A nationwide database study performed on 533,044 patients with AF or atrial flutter showed an increased risk of death in patients who also had cancer (OR 1.81, 95%CI 1.78–1.85).65

Patients with cancer in the ROCKET AF trial had a higher rate of non-cardiovascular death (HR 1.47, 95%CI 1.04–2.07) compared with those without cancer, mainly due to causes related to cancer (HR 1.30, 95%CI 1.16–1.47).44 An even higher risk of death was reported in the ENGAGE AF-TIMI 48 trial,45 in which 1153 new

DOACs for treating patients with AF and cancer

As the presence of cancer may increase both ischemic and bleeding risk in patients with AF,67 the benefits and advantages of DOAC may be more evident in this subgroup of patients. The bulk of the evidence today supports using DOACs instead of VKA in most patients with AF and cancer.68 The safety and effectiveness of DOACs in the setting of cancer have been recently investigated. A post-hoc analysis from the ARISTOTLE study showed that, in patients with active cancer, compared with warfarin,

Factors affecting management of anticoagulation treatment in patients with AF and cancer

Several factors may affect the management of oral anticoagulation in patients diagnosed with AF and cancer, including 1) drug-drug interactions between oral anticoagulants and anticancer therapies, 2) patient-related characteristics (e.g., thrombocytopenia, liver damage), 3) the presence of other indications for anticoagulants (e.g., VTE, intracardiac thrombus, prosthetic heart valve) and 4) availability of reversal agent.

Management of oral anticoagulation in specific situations

The choice of anticoagulant may change according to cancer treatment, as LMWH, VKAs and DOACs have benefits and drawbacks that should be evaluated on an individual basis. Thus, the anticoagulation treatment may vary in patients undergoing CT, RT, or surgical interventions (Fig. 2). Independently from the type of cancer treatment, the eligibility of patients for DOACs should always be considered, as DOACs are associated with a lower rate of major and ICH compared to VKAs.

However, in patients

Conclusions and perspectives

In conclusion, there is an increased risk of developing AF in patients with cancer, which is particularly high in the first 3 months after the diagnosis of cancer, as a consequence of 1) increased detection of AF during the work-up of cancer, 2) a possible actual increase in AF incidence, perhaps due to systemic inflammation and 3) antineoplastic drugs that increase the risk of AF.

There still are some grey zones that will need further research in the field of oncology and AF. The frequencies of

Funding source

None.

Declaration of Competing Interest

None.

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