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Introduction: Novel oral anticoagulants have been tested against warfarin for atrial fibrillation, yet no direct comparison is available. We thus aimed to perform pair-wise (direct) and warfarin-adjusted network (i.e. indirect) meta-analyses of novel oral anticoagulants for atrial fibrillation. Methods: Databases were searched for randomized warfarin-controlled trials of novel anticoagulants for non- valvular atrial fibrillation. The primary end-point was long-term stroke/systemic embolism. Odds ratios (95% intervals) were computed with RevMan and WinBUGS. Results: Seven trials (52701 patients) were included, focusing on apixaban, dabigatran, edoxaban and rivaroxaban. Pair-wise meta-analysis showed that after a weighted average of 23 months these novel anticoagulants lead to significant reductions in the risk of stroke/systemic embolism (odds ratio = 0.81 [0.71-0.92], I2 = 23%) and all cause death (odds ratio = 0.88 [0.82-0.95], I2 = 0%) in comparison to warfarin. Network meta-analysis showed that apixaban and dabigatran proved similarly superior to warfarin in preventing stroke/systemic embolism (odds ratio = 0.78 [0.62-0.96] for apixaban vs warfarin; odds ratio = 0.66 [0.52-0.84] for high-dose dabigatran vs warfarin; odds ratio for apixaban vs high-dose dabigatran = 1.17 [0.85-1.63]), but apixaban was associated with fewer major bleedings (odds ratio = 0.73 [0.57-0.93]) and drug discontinuations (odds ratio = 0.64 [0.52-0.78]) than dabigatran. Rivaroxaban did not reduce stroke/systemic embolism (odds ratio = 0.87 [0.71- 1.07]) or major bleedings in comparison to warfarin (odds ratio = 0.87 [0.71-1.07]) and was associated with more major bleedings in comparison to apixaban (odds ratio = 1.52 [1.19-1.92]). Data for edoxaban were inconclusive. Conclusions: Novel oral anticoagulants appear as a very promising treatment option for atrial fibrillation. [ABSTRACT FROM AUTHOR]

The hierarchy of evidence based medicine postulates that systematic reviews of homogenous randomized trials represent one of the uppermost levels of clinical evidence. Indeed, the current overwhelming role of systematic reviews, meta-analyses and meta-regression analyses in evidence based heath care calls for a thorough knowledge of the pros and cons of these study designs, even for the busy clinician. Despite this sore need, few succinct but thorough resources are available to guide users or would-be authors of systematic reviews. This article provides a rough guide to reading and, summarily, designing and conducting systematic reviews and meta-analyses. [ABSTRACT FROM AUTHOR]