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CLINICAL STATEMENTS AND GUIDELINES

January 2, 2024 Circulation. 2024;149:e1–e156. DOI: 10.1161/CIR.0000000000001193 e110

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

cancer therapies associated with a higher risk of AF, evaluation and optimization of cardiovascular risk factors or disease by a cardiologist could be beneficial in decreasing incident and recurrent AF and associated cardiovascular events, although no data are available specifically in patients with cancer. Furthermore, elevated natriuretic peptides or a history of previous AF can identify patients at higher risk of AF after major thoracic cancer surgery.26,27

3 No large RCTs are available that compare DOACs

to warfarin in patients with AF and cancer. A metaanalysis of post-hoc analyses of RCTs and retrospective observational studies that compared DOACs with warfarin in patients with AF and cancer (n=229 221) demonstrated a lower risk of stroke or systemic embolism (RR, 0.65 [95% CI, 0.52-0.81]; P=0.001) and major bleeding (RR, 0.68 [95% CI, 0.50-0.92]; P=0.01) with DOACs.8 This meta-analysis included post hoc analyses of patients with cancer and AF from the ROCKET AF (rivaroxaban versus warfarin), ENGAGE TIMI-48 (edoxaban versus warfarin), and ARISTOTLE (apixaban versus warfarin) trials. These findings were consistent in patients defined as having active cancer, although definitions of active cancer varied by study. An additional large retrospective observation study comparing DOACs to warfarin in patients with active cancer demonstrated a lower risk of the composite endpoint of ischemic stroke/intracranial bleeding in patients taking DOACs compared with VKA (adjusted HR, 0.65 [95% CI, 0.48-0.88]).7 Although most of the data in this patient population came from retrospective observational studies that may be prone to selection bias, findings are largely consistent with post hoc analyses from RCTs and the major RCTs comparing DOACs with VKA in general. Special consideration should be given to patient bleeding risk and antineoplastic drug interactions in this patient population (Table 30).18,19

10.15 CKD and Kidney Failure

CKD and kidney failure (formerly end-stage renal disease) share common risk factors with AF, such as hypertension and diabetes, and unsurprisingly, CKD and AF are associated in a disproportionate manner. In population studies, baseline serum creatinine, eGFR, and proteinuria were strongly associated with incident of AF during followup.1,2 AF at baseline also predicted new renal dysfunction or proteinuria, suggesting a bidirectional relationship between CKD and AF.2 In an insurance database of 206 229 adults with confirmed CKD, over a mean follow-up of 5 years, there was a 67% increased rate of kidney failure among patients with CKD who developed incident AF compared with those without AF, even after adjustment for baseline factors.3 Data on the management of AF in patients with CKD is limited because the major trials of rate control, rhythm control, and catheter ablation have generally not reported eGFR or CKD as a baseline variable or excluded such patients. Antiarrhythmic drug doses are adjusted based on pharmacokinetic data and clinical experience, with amiodarone being the only drug that does not require dose adjustment in patients with CKD or those receiving dialysis. Catheter ablation is feasible, although particular attention must be paid to fluid balance when using irrigated radiofrequency catheters. Anticoagulation in patients with CKD and AF is covered in Section 6.8.4 (“Chronic Kidney Disease [CKD]/Kidney Failure”).

10.16 Anticoagulation Use in Patients With

Liver Disease Recommendations for Anticoagulation Use in Patients With Liver Disease Referenced studies that support the recommendations are summarized in the Online Data Supplement. COR LOE Recommendations

2a B-NR 1 For patients with AF who are at increased risk of

systemic thromboembolism and mild or moderate liver disease (Child-Pugh* class A or B), OAC therapy is reasonable in the absence of clinically significant liver disease–induced coagulopathy or thrombocytopenia.1–7

2a B-NR 2 For patients with AF who are at increased risk of

systemic thromboembolism and mild or moderate liver disease (Child-Pugh class A or B) and who are deemed to be candidates for anticoagulation, it is reasonable to prescribe DOACs (Child-Pugh class A: any DOAC; Child-Pugh class B: apixaban, dabigatran, or edoxaban) over warfarin.1,7–11

3: Harm C-LD 3 For patients with AF and moderate liver disease

(Child-Pugh class B) at increased risk of systemic thromboembolism, rivaroxaban is contraindicated due to the potentially increased risk of bleeding.12

*Child-Pugh scoring: the severity of liver disease, primarily cirrhosis in patients with diagnosed liver disease. Child-Pugh A (mild): 5-6 points; Child-Pugh B (moderate): 7-9 points; Child-Pugh C (severe): 10-15 points. The score is based on the 5 variables: encephalopathy (none=1 point, grade 1 and 2=2 points, grade 3 and 4=3 points); ascites (none=1 point, slight=2 points, moderate=3 points); total bilirubin (<2 mg/mL=1 point, 2-3 mg/mL=2 points, >3 mg/mL=3 points); albumin (>3.5 mg/mL=1 point, 2.8-3.5 mg/mL=2 points, <2.8 mg/mL=3 points); INR (<1.7=1 point, INR 1.7-2.2=2 points, INR >2.2=3 points).

Table 30.  Special Considerations for Anticoagulation in Patients With AF on Active Cancer Treatment Increased bleeding risk High bleeding risk estimators (eg, HAS-BLED) Thrombocytopenia (platelet <50 000/uL) Intracranial malignancy Gastrointestinal malignancy History of major bleeding Severe kidney dysfunction (eGFR <30 mL/ min/1.73 m2) Drug interactions P-glycoprotein inducers or inhibitors CYP3A4 inducers or inhibitors AF indicates atrial fibrillation; eGFR, estimated glomerular filtration rate; and HAS-BLED, hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio (INR), elderly (age ≥65 years), drugs/alcohol concomitantly).

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