Table 1.

PICOS criteria for inclusion and exclusion of systematic review.

	Inclusion Criteria	Exclusion Criteria
Population	Patients with NVAF receiving any of the treatments below. All studies in the SLR must include ≥90% patients with NVAF. SLRs including studies with <90% patients with NVAF must report data separately for the NVAF studies	Not a population of interest (i.e., non-NVAF patients) Studies of patients receiving ablation, cardioversion, or left-atrial appendage closure
Intervention/comparator	DOACs (apixaban, dabigatran, rivaroxaban, edoxaban) and warfarin studies need to have compared 1 or more DOACs and/or warfarin	Studies not reporting outcomes for population of interest
Outcome	Clinical outcomes: • Stroke/systemic embolism • Major bleeding (ISTH or modified ISTH). • Patients with CHADS2 ≥3 • Elderly patients (age ≥ 75 years) • Patients with heart failure Doses included: Apixaban: 5 mg or 2.5 mga Rivaroxaban: 20 mg or 15 mg Dabigatran: 150 mg or 110 mg Edoxaban: 60 mg	SLRs/NMAs of observational studies, nonsystematic reviews, primary research trials, primary observational studies, case reports, case series, narrative reviews Letters to the editor, guidelines, meeting abstracts In vitro pharmacodynamic or pharmacokinetic studies only, animal studies, genetic studies only
Study design	SLR of randomized controlled trials

PICOS, patients, intervention, comparator, outcomes, study design; DOAC, direct oral anticoagulant; ISTH, International Society on Thrombosis and Hemostasis; CHADS₂, [congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke (double weight)]; NMA, network meta-analysis; NVAF, nonvalvular atrial fibrillation; SLR, systematic literature review.

^aAny network meta-analysis comparison of apixaban 2.5 mg only with another DOAC was not included.