Table 1.
Exclusion criteria
| Mechanical heart valves, moderate to severe mitral stenosis, or new implantation (within 3 months prior to randomization) of a bioprosthetic heart valve, with or without AF |
| Transient AF or AF of a reversible nature (eg, myocarditis, postsurgery, ionic disturbances, thyrotoxicosis, pneumonia, or severe anemia) |
| Post‐stroke or a systemic thromboembolic event within the past 6 months prior to randomization |
| Thrombus in the LAA, left atrium, left ventricle, or aorta; an intracardial mass; or history of LAA occlusion/exclusion (either by surgery or by a procedure) |
| MI within 2 months prior to randomization or CABG surgery within 3 months prior to randomization |
| Signs of bleeding, history of clinically relevant ISTH‐defined bleeding, or conditions associated with high risk of bleeding; overt GI bleeding or active ulcer within the previous year |
| Recent severe trauma, major surgery, or deep‐organ biopsy |
| Active infective endocarditis |
| Uncontrolled HTN (BP >170/100 mm Hg) |
| Hemorrhagic disorder including known or suspected hereditary or acquired bleeding or coagulation disorder in the last 12 months prior to randomization |
| Contraindication for edoxaban, VKA, LMWH, or heparin therapy including known allergies, hypersensitivity, or intolerance to any component of these drugs or their excipients |
| Receiving DAPT or planned to receive DAPT during the study |
| Concomitant use of UFH, LMWH, heparin derivatives (eg, fondaparinux), or OACs; bridging with LMWH around the ablation procedure is prohibited |
| Chronic use of medicines affecting hemostasis, including higher doses of ASA (100 mg/d allowed) or chronic oral or parenteral intake of NSAIDs on ≥4 d/wk (use of NSAIDs via other routes is not restricted) |
| Active liver disease or persistent (confirmed by repeat assessments at least a week apart) elevation of liver enzymes/bilirubin: |
| ALT or AST ≥2× ULN |
| TBL ≥1.5× ULN (subjects whose elevated TBL is due to known Gilbert syndrome may be included in the study) |
| Hepatic disease associated with coagulopathy and clinically relevant bleeding risk |
| Kidney failure (calculated CrCl <15 mL/min) |
| Hb <10 g/dL, or platelet count <100 000 cells/μL or WBC count <3000 cells/μL |
| Preplanned invasive diagnostic or therapeutic procedures/interventions (other than endoscopy) during the study period in which bleeding is anticipated; a planned procedure using laser catheter ablation or other forms of catheter ablation different from radiofrequency or cryoballoon |
| Participation in any other interventional trial; previous randomization in this study |
| Active cancer undergoing chemotherapy, radiation, or major surgery within the next 5 months |
| Significant active/uncontrolled concurrent medical illness; life expectancy <6 months |
| Known drug or alcohol dependence within the past 12 months prior to randomization, as judged by the investigators |
| Female patients of childbearing potential not using highly effective contraceptiona; female patients who are pregnant or breastfeeding |
| Patients considered by the investigators to have a condition that would place the patient at increased risk of harm; patients unlikely to comply with the protocol |
Abbreviations: AF, atrial fibrillation; ALT, alanine transaminase; ASA, acetylsalicylic acid (aspirin); AST, aspartate transaminase; BP, blood pressure; CABG, coronary artery bypass grafting; CrCl, creatinine clearance; DAPT, dual antiplatelet therapy; GI, gastrointestinal; Hb, hemoglobin; HTN, hypertension; ISTH, International Society on Thrombosis and Haemostasis; LAA, left atrial appendage; LMWH, low‐molecular‐weight heparin; MI, myocardial infarction; NSAID, nonsteroidal anti‐inflammatory drug; OAC, oral anticoagulant; TBL, total bilirubin; UFH, unfractionated heparin; ULN, upper limit of normal; VKA, vitamin K antagonist; WBC, white blood cell.
a
Females taking oral contraceptives should have been on therapy for ≥3 months.