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与华法林相比,肾功能与非维生素K口服抗凝剂在房颤患者安全性和疗效结果方面的研究:一项系统评价和Meta回归分析

Renal function and non-vitamin K oral anticoagulants in comparison with warfarin on safety and efficacy outcomes in atrial fibrillation patients: a systemic review and meta-regression analysis.

作者信息

Nielsen Peter Brønnum, Lane Deirdre A, Rasmussen Lars Hvilsted, Lip Gregory Y H, Larsen Torben Bjerregaard

机构信息

Department of Cardiology, Aalborg AF Study Group, Aalborg University Hospital, Aalborg, Denmark,

出版信息

Clin Res Cardiol. 2015 May;104(5):418-29. doi: 10.1007/s00392-014-0797-9. Epub 2014 Nov 22.

Abstract

OBJECTIVE

To investigate the relative effect of warfarin versus non-vitamin K oral anticoagulants (NOACs) in thrombotic and bleeding outcomes in subgroups of atrial fibrillation (AF) patients with varying degrees of renal dysfunction.

METHODS

Systemic review and meta-regression analyses on NOACs versus warfarin, supplemented with indirect comparisons were conducted. The eligibility criteria for inclusion were randomised controlled trials comparing NOACs against warfarin for stroke prevention in AF patients. Outcomes of interest were stroke or systemic embolism (SE) and major bleeding.

RESULTS

Five studies comprising 72,845 AF patients randomised to either a NOAC or warfarin were included in the meta-regression analysis. A shift in strata from no renal impairment to renal impairment resulted in a non-significant impact on bleeding and stroke/SE, indicating similar safety and efficacy, despite renal function status. Apixaban was associated with less major bleeding compared to dabigatran and rivaroxaban but not edoxaban in patients with moderate renal impairment. For efficacy outcomes, only dabigatran 150 mg was statistically significantly favoured compared to edoxaban 30 mg. For efficacy outcomes in mild renal impairment, both dabigatran 150 mg and rivaroxaban 10 mg (J-ROCKET) were statistically significantly favoured against edoxaban 30 mg.

CONCLUSION

Non-vitamin K oral anticoagulants had similar efficacy and safety compared to warfarin across different levels of renal function. Indirect comparisons suggest that apixaban and edoxaban were associated with a better safety profile in patients with moderate renal impairment. However, caution is warranted when interpreting indirect comparisons of drugs investigated in different trials. Prescribers should fit the most appropriate NOAC to the AF patient characteristics (and vice versa) to individualise effective stroke prevention.

摘要

目的

探讨华法林与非维生素K口服抗凝药(NOACs)对不同程度肾功能不全的心房颤动(AF)患者血栓形成和出血结局的相对影响。

方法

对NOACs与华法林进行系统评价和meta回归分析,并辅以间接比较。纳入标准为比较NOACs与华法林预防AF患者卒中的随机对照试验。感兴趣的结局为卒中或全身性栓塞(SE)和大出血。

结果

meta回归分析纳入了5项研究,共72845例随机接受NOAC或华法林治疗的AF患者。从无肾功能损害到肾功能损害的分层变化对出血和卒中/SE无显著影响,表明无论肾功能状态如何,安全性和有效性相似。在中度肾功能不全患者中,与达比加群和利伐沙班相比,阿哌沙班大出血较少,但与依度沙班相比无差异。对于疗效结局,仅达比加群150 mg在统计学上显著优于依度沙班30 mg。对于轻度肾功能不全的疗效结局,达比加群150 mg和利伐沙班10 mg(J-ROCKET)在统计学上均显著优于依度沙班30 mg。

结论

在不同肾功能水平下,非维生素K口服抗凝药与华法林的疗效和安全性相似。间接比较表明,阿哌沙班和依度沙班在中度肾功能不全患者中安全性更好。然而,在解释不同试验中研究药物的间接比较时应谨慎。处方者应根据AF患者的特征选择最合适的NOAC(反之亦然),以实现有效的卒中预防个体化。

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