Risks and benefits of direct oral anticoagulants versus warfarin in a real world setting: cohort study in primary care [在真实环境中，直接口服抗凝药和华法林的风险与益处：初级保健中的队列研究]

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BMJ 2018; 362 doi: https://doi.org/10.1136/bmj.k2505 (Published 04 July 2018)
Cite this as: BMJ 2018;362:k2505

Authors
Yana Vinogradova, Carol Coupland, Trevor Hill, Julia Hippisley-Cox

Abstract
Objective To investigate the associations between direct oral anticoagulants (DOACs) and risks of bleeding, ischaemic stroke, venous thromboembolism, and all cause mortality compared with warfarin.

Design Prospective open cohort study.

Setting UK general practices contributing to QResearch or Clinical Practice Research Datalink.

Participants 132 231 warfarin, 7744 dabigatran, 37 863 rivaroxaban, and 18 223 apixaban users without anticoagulant prescriptions for 12 months before study entry, subgrouped into 103 270 patients with atrial fibrillation and 92 791 without atrial fibrillation between 2011 and 2016.

Main outcome measures Major bleeding leading to hospital admission or death. Specific sites of bleeding and all cause mortality were also studied.

Results In patients with atrial fibrillation, compared with warfarin, apixaban was associated with a decreased risk of major bleeding (adjusted hazard ratio 0.66, 95% confidence interval 0.54 to 0.79) and intracranial bleeding (0.40, 0.25 to 0.64); dabigatran was associated with a decreased risk of intracranial bleeding (0.45, 0.26 to 0.77). An increased risk of all cause mortality was observed in patients taking rivaroxaban (1.19, 1.09 to 1.29) or on lower doses of apixaban (1.27, 1.12 to 1.45). In patients without atrial fibrillation, compared with warfarin, apixaban was associated with a decreased risk of major bleeding (0.60, 0.46 to 0.79), any gastrointestinal bleeding (0.55, 0.37 to 0.83), and upper gastrointestinal bleeding (0.55, 0.36 to 0.83); rivaroxaban was associated with a decreased risk of intracranial bleeding (0.54, 0.35 to 0.82). Increased risk of all cause mortality was observed in patients taking rivaroxaban (1.51, 1.38 to 1.66) and those on lower doses of apixaban (1.34, 1.13 to 1.58).

Conclusions Overall, apixaban was found to be the safest drug, with reduced risks of major, intracranial, and gastrointestinal bleeding compared with warfarin. Rivaroxaban and low dose apixaban were, however, associated with increased risks of all cause mortality compared with warfarin.