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Aims: The aim of this study was to compare the clinical effectiveness and safety of direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) in routine clinical practice. Methods: This retrospective cohort study used linked administrative data. The study population (n = 14 577) included patients with a diagnosis of AF (confirmed in hospital) who initiated DOAC treatment in Scotland between August 2011 and December 2015. Multivariate Cox proportional hazard models were used to estimate hazard ratios of thromboembolic events, mortality and bleeding events. Results: No differences between the DOACs were observed with regard to the risk of stroke, systemic embolism or cardiovascular death. In contrast, the risk of myocardial infarction was higher among patients prescribed apixaban in comparison to those on rivaroxaban (HR 1.67, 95% CI 1.02‐2.71), and all‐cause mortality was higher among rivaroxaban patients in contrast to both apixaban (1.22 [1.01–1.47]) and dabigatran (1.55 [1.16–2.05]) patients; rivaroxaban patients also had a higher risk of pulmonary embolism than apixaban patients (5.27 [1.79–15.53]). The risk of other major bleeds was higher among rivaroxaban patients compared to apixaban (1.50 [1.10–2.03]) and dabigatran (1.58 [1.01–2.48]) patients; the risks of gastrointestinal bleeds and overall bleeding were higher among rivaroxaban patients than among apixaban patients (1.48 [1.01–2.16] and 1.52 [1.21–1.92], respectively). Conclusions: All DOACs were similarly effective in preventing strokes and systemic embolisms, while patients being treated with rivaroxaban exhibited the highest bleeding risks. Observed differences in the risks of all‐cause mortality, myocardial infarction and pulmonary embolism warrant further research. [ABSTRACT FROM AUTHOR]

The development of evidence-based guidelines requires scrupulous attention to the method of critical appraisal. Many critical appraisal systems give 'gold standard' status to randomised controlled trials (RCTs) due to their ability to limit bias. While guidelines with a prominent research base consisting of RCTs have been well served by such systems, specialist societies with research bases consisting of a wide range of study designs have been at a disadvantage, potentially leading to inappropriately low grades being given for recommendations. A review of the Scottish Intercollegiate Guidelines Network, the Grading of Recommendations Assessment, Development and Evaluation, the Graphic Appraisal Tool for Epidemiology and the National Service Framework for Long Term Conditions grading systems was therefore undertaken. A matrix was developed suggesting the optimum grading system for the type of guideline being developed or question being addressed by a specialist society. [ABSTRACT FROM AUTHOR]