PRAGUE‐17 2020.

Methods	Investigator‐initiated, multicentre, prospective, open‐label, randomised, noninferiority trial conducted at 10 cardiac centres in the Czech Republic.
Participants	Moderate‐ or high‐risk patients with nonvalvular AF were eligible if indicated for anticoagulation and had: 1) history of bleeding requiring intervention or hospitalization; 2) history of a cardioembolic event while taking anticoagulation agents; or 3) a moderate to high risk profile, defined as CHA2DS2‐VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke, transient ischemic attack, or thromboembolism, vascular disease, age 65–74 years, sex category [female]) of ≥3 plus HAS‐BLED (uncontrolled hypertension, abnormal renal or liver function, stroke, bleeding, labile international normalized ratio, elderly, drugs or alcohol) of ≥2. Key exclusion criteria included mechanical valve prosthesis, mitral stenosis, comorbidities other than AF mandating anticoagulation, patent foramen ovale with large atrial septal aneurysm, mobile aortic plaque, symptomatic carotid arterial atherosclerosis, clinically significant bleeding within 30 days, cardioembolic event within 30 days, and creatinine clearance of <30 mL/min.
Interventions	Left atrial appendage closure versus non‐vitamin K direct oral anticoagulant (DOAC). Patients randomised to the DOAC group could receive either rivaroxaban, apixaban, or dabigatran at the manufacturer‐recommended dose.
Outcomes	The primary outcome was a composite of safety and efficacy characteristics of both strategies: 1) stroke (ischaemic or haemorrhagic) or transient iachaemic attack (TIA)2) systemic embolism; 3) clinically significant bleeding; 4) cardiovascular death; or 5) significant peri‐procedural or device‐related complications. Clinically significant bleeding was a composite of major and nonmajor clinically relevant bleeding (NMCRB), according to the International Society on Thrombosis and Hemostasis (ISTH) criteria. Major bleeding includes either a decrease in haemoglobin of ≥2.0 g/dL during a 24‐h period, transfusion of ≥2 units of packed red cells, bleeding at a critical site (intracranial, intraspinal, intraocular, pericardial, intramuscular with compartment syndrome, or retroperitoneal), or fatal bleeding. NMCRB is defined as bleeding requiring hospitalization or an invasive procedure but not meeting ISTH major criteria. Complications included pericardial effusion requiring drainage/pericardiocentesis or surgery, cardioembolism, peri‐procedural bleeding requiring surgical revision or transfusion, device embolisation, device‐related thrombus with cardioembolism, or others as assessed by the operator and clinical endpoint committee (CEC). Secondary endpoints included the individual components of the primary endpoint.
Notes

a Patients such as those not eligible for continued administration at the approved dosage for the drug due to concerns about bleeding risk, or those who have not been administered available oral anticoagulants at the approved dosage but are expected to have a high bleeding risk from available oral anticoagulants at the approved dosage.

b For warfarin, INR controlled between 1.6 and 2.6.

c Subcutaneous bleeding will be included if there is at least 1 hematoma with a maximal diameter of at least 5 cm, and urinary findings will be included if frank hematuria is observed.

d History of mitral valve repair is allowed in the trial. CHADS2, Congestive heart failure, Hypertension, Age, Diabetes, prior Stroke or transient ischaemic attack; INR, international normalized ratio.