Thus, for these choices that are not expected to result in a difference in mor- tality, for every 1,000 patients treated for 1 year, if the number of nonfatal strokes prevented is less than one-third of the number of nonfatal major extracranial bleeds caused by a given antithrom- botic therapy, we have recommended against that intervention. If the number of nonfatal strokes prevented is appreciably more than one-third of the number of nonfatal major extracranial bleeding events that result from a given antithrombotic therapy, we have recommended in favor. Making these trade-offs requires not only estimates regarding average patient values for the relevant outcomes but also best esti- mates of (1) the effect of a given treatment on these outcomes against a given comparator (ie, relative risk) and (2) the absolute event rates for these outcomes in untreated patients (or, for PICO questions of a treatment vs an active comparator, the absolute event rates in patients receiving the active comparator). In the following section, we present the methods used to obtain these estimates for our guidelines. 1.3 Estimating the Magnitude of Treatment Effect For each clinical question, we extracted data regarding the previously discussed outcomes from the relevant clinical trials. When there were multiple randomized controlled trials (RCTs) addressing the same clinical question, we conducted meta- analyses using random-effects models and the Mantel-Haenszel method to obtain pooled estimates of treatment effect, expressed as relative risk. For studies that did not report the proportion of strokes that were fatal and nonfatal, we used all available data in the published report to obtain a best estimate of the effect of The article ends with a discussion of practical issues in the use of adjusted-dose vitamin K antago- nist (VKA) therapy in patients with AF and sugges- tions for future research. 