Further research is very unlikely to change our con dence in the estimate of effect Weak (conditional) recommendation, Moderate-quality evidence Bene ts closely balanced with risks and burden We are moderately con dent in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Best action may differ depending on circumstances or patients or societal values. Higher quality research may well have an important impact on our con dence in the estimate of effect and may change the estimate Weak (conditional) recommendation, Low quality evidence Uncertainty in the estimates of bene ts, risks, and burden; bene ts, risk and burden may be closely balanced Our con dence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Other alternatives may be equally reasonable. Higher quality research is likely to have an important impact on our con dence in the estimate of effect and may well change the estimate (Continued) Evidence-Based Medicine [ # C H E S T N O V E M B E R ] Consistent with the ninth edition of the guideline, the outcomes most relevant to patients with AF include death, nonfatal stroke, systemic embolism, nonfatal major extracranial bleeding, and the burden and lifestyle limitations associated with outpatient antithrombotic To facilitate decision-making, the term stroke in this guideline includes both ischemic stroke and hemorrhagic stroke, which together with systemic embolism was the principal outcome in most stroke prevention trials. Additional considerations were all- cause and cardiovascular mortality. For bleeding outcomes, we focused on major bleeding, which was the principal safety outcome in most stroke prevention trials. Major bleeding included intracranial bleeding, the most severe and disabling form of anticoagulant-related bleeding. 