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CLINICAL STATEMENTS AND GUIDELINES

Circulation. 2024;149:e1–e156. DOI: 10.1161/CIR.0000000000001193 January 2, 2024 e109

Joglar et al 2023 Guideline for the Diagnosis and Management of Atrial Fibrillation

AF and cancer are at an increased risk for major bleeding.18 They also are commonly on antineoplastic agents, which may have important drug interactions with OACs.19 Thus, these factors should be carefully considered in determining indication and choice of OAC.

Recommendation-Specific Supportive Text 1.	 In patients with cancer who develop AF in the pres-

ence of cancer therapeutics associated with an increased risk of incident AF (Table 29), the first approach usually consists of optimizing AF control while continuing cancer therapy. However, if AF control cannot be achieved, decisions regarding dose reduction of the cancer therapy or even stoppage can only be made in concert with the oncology team and SDM with the patient. Drugdrug interactions between cancer, antiarrhythmic, rate-control, and anticoagulant therapies are common and require close attention.1 For example, in the case of BTK inhibitors, CYP3A inhibitors such as amiodarone, dronedarone, verapamil, and diltiazem are usually avoided, due to the associated risk of elevation in ibrutinib levels.1 Further, ibrutinib can raise levels of digoxin, a P-glycoprotein substrate.1 Therefore, beta blockers are considered the best option for rate control in BTK inhibitor-associated AF. If additional agents are needed for AF control, any concomitant reduction in dose of ibrutinib is guided by oncology.1 Further, QTc prolongation, which is more common in patients with cancer due to several cancer therapies, antiemetics, antibiotics, and electrolyte derangements, can be further exacerbated by QT-prolonging antiarrhythmic agents.3 Structured screening by pharmacists for potential drug-drug interactions could provide benefit.2

2 Certain medical cancer therapies can increase the

risk of incident AF (Table 29). Patients with cancer and AF are older and have higher rates of hypertension, MI, and HF compared with those who do not develop AF.13–15 The development of perioperative AF has been strongly associated with perioperative complications.20 In general, patients with cancer and CVD may be undertreated with GDMT or less often referred to specialists for cardiovascular care.21 Optimization of cardiovascular conditions such as hypertension and HF may decrease the risk of incident AF, AF recurrence, and of major adverse cardiovascular events, including stroke.22–25 Therefore, in patients without a history of AF, or those with previous history of AF, who are to be started on

Table 29.  Medical Cancer Therapy Associated With Increased Risk of AF (>1%)

Frequency Reported in Clinical Trials

and Observational Studies

Cancer Therapy Common: Incidence

1%-10% Frequent:

>10% Comments

Anthracyclines Doxorubicin, epirubicin, idarubicin, mitoxantrone X AF may be a secondary result of anthracycline cardiotoxicity; studies in different populations demonstrate variable risk of AF Antimetabolites Clofarabine combined with cytarabine 5FU Cepecitabine Gemcitabine X X X X Alkylating agents Cyclophosphamide Melphalan + stem cell transplantation X X* *Stem cell transplantation is associated with an increased risk of AF,28,29 and the risk may be higher with melphalan-associated regimens. Immunomodulatory drugs Lenalidomide Interleukin-2 X X Given rates reported from patients with multiple myeloma, AF due to underlying cardiac AL amyloid may contribute TKIs Ibrutinib (BTKi) Acalbrutinib (second-generation BTKi) Zanubrutinib (second-generation BTKi) Ponatinib (BCR-ABL TKI) and other TKIs (eg, trametinib, osimertinib, nilotinib, ribociclib) VEGF inhibitor Sorafenib in combination with 5FU BRAF inhibitor Vemurafenib X†

X X X

X

X X† †Reported AF rates with ibrutinib have varied across trials (4%-18%),6,30 partly related to varying duration of follow-up and patient factors. Second-generation BTKis have more selective BTK activity and are associated with a lower incidence of AF than ibrutinib.31

Based on FDA adverse event reporting system4

CAR T-cell therapy Tisagenlecleucel Axicabtagene ciloleucel X X Monoclonal antibodies Rituximab X Table developed by 2023 Atrial Fibrillation Guideline Writing Committee. Data extracted from Buza et al32 and Fradley et al.33 AF indicates atrial fibrillation; BTKi, Bruton’s kinase inhibitor; CAR, chimeric antigen receptor; FDA, US Food and Drug Administration; 5FU, 5 fluorouracil; and TKI, tyrosine kinase inhibitor.

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