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非瓣膜性心房颤动患者口服抗凝药预防卒中持续性的早期真实世界证据:一项英国初级医疗保健队列研究

Early real-world evidence of persistence on oral anticoagulants for stroke prevention in non-valvular atrial fibrillation: a cohort study in UK primary care.

作者信息

Johnson Michelle E, Lefèvre Cinira, Collings Shuk-Li, Evans David, Kloss Sebastian, Ridha Essra, Maguire Andrew

机构信息

OXON Epidemiology, London, UK.

Department of Worldwide Health Economics & Outcomes Research, Bristol-Myers Squibb, Paris, France.

出版信息

BMJ Open. 2016 Sep 26;6(9):e011471. doi: 10.1136/bmjopen-2016-011471.

Abstract

OBJECTIVES

To examine the characteristics and persistence in patients newly initiated with oral anticoagulants (OACs) for stroke prevention in non-valvular atrial fibrillation (NVAF).

DESIGN

Cohort study in Clinical Practice Research Datalink.

SETTING

UK primary care.

PARTICIPANTS

15 242 patients with NVAF newly prescribed apixaban, rivaroxaban, dabigatran or vitamin K antagonists (VKAs) between 1 December 2012 and 31 October 2014. 13 089 patients were OAC naïve.

OUTCOME MEASURES

Patient characteristics and risk of non-persistence compared to apixaban using Cox regression models over the entire follow-up and using a time-partitioned approach to handle non-proportional hazards.

RESULTS

Among the OAC naïve patients, VKAs were most common (78.1%, n=10 218), followed by rivaroxaban (12.1%, n=1589), dabigatran (5.7%, n=741) and apixaban (4.1%, n=541). High baseline stroke risk (CHADSVASc ≥2) ranged from 80.2% (dabigatran) to 88.4% (apixaban and rivaroxaban). History of stroke and bleeding was the highest among apixaban (23.7% and 31.6%) and lowest among VKA patients (15.9% and 27.5%). Across the entire follow-up period, adjusting for differences in characteristics, there was no evidence of a difference in non-persistence between VKA and apixaban (HR 0.92 (95% CI 0.68 to 1.23)). Non-persistence was higher with dabigatran (HR 1.67 (1.20 to 2.32)) and rivaroxaban (HR 1.41 (1.02 to 1.93)) than apixaban. Using the partitioned approach, non-persistence was lower with VKA (HR 0.33 (0.22 to 0.48)), and higher with dabigatran (HR 1.65 (1.08 to 2.52)) compared to apixaban in the first 2 months of follow-up. After 2 months, non-persistence was higher with VKA (HR 1.70 (1.08 to 2.66)) and dabigatran (HR 2.10 (1.30 to 3.41)). Pooling OAC naïve and experienced patients, non-persistence was also higher with rivaroxaban compared to apixaban after 2 months of follow-up (HR 1.69 (1.19 to 2.39)).

CONCLUSIONS

Observed differential prescribing of OACs can result in channelling bias in comparative effectiveness research. Persistence patterns changed over follow-up time, but there are indications of improved persistence rates with apixaban over other OACs in the UK. A larger study with longer follow-up is needed to corroborate findings. This study is registered on ClinicalTrials.gov (NCT02488421).

摘要

目的

研究新开始使用口服抗凝药(OAC)预防非瓣膜性心房颤动(NVAF)患者中风的特征及持续性。

设计

临床实践研究数据链中的队列研究。

地点

英国初级医疗保健机构。

参与者

2012年12月1日至2014年10月31日期间新开具阿哌沙班、利伐沙班、达比加群或维生素K拮抗剂(VKA)的15242例NVAF患者。13089例患者此前未使用过OAC。

观察指标

使用Cox回归模型在整个随访期间以及采用时间分割方法处理非比例风险,对比阿哌沙班,观察患者特征及不持续用药的风险。

结果

在未使用过OAC的患者中,VKA最为常见(78.1%,n = 10218),其次是利伐沙班(12.1%,n = 1589)、达比加群(5.7%,n = 741)和阿哌沙班(4.1%,n = 541)。高基线中风风险(CHADSVASc≥2)范围从80.2%(达比加群)至88.4%(阿哌沙班和利伐沙班)。中风和出血史在阿哌沙班患者中最高(分别为23.7%和31.6%),在VKA患者中最低(分别为15.9%和27.5%)。在整个随访期间,校正特征差异后,没有证据表明VKA和阿哌沙班在不持续用药方面存在差异(风险比0.92(95%置信区间0.68至1.23))。达比加群(风险比1.67(1.20至2.32))和利伐沙班(风险比1.41(1.02至1.93))的不持续用药率高于阿哌沙班。采用分割方法,在随访的前2个月,与阿哌沙班相比,VKA的不持续用药率较低(风险比0.33(0.22至0.48)),达比加群较高(风险比1.65(1.08至2.52))。2个月后,VKA(风险比1.70(1.08至2.66))和达比加群(风险比2.10(1.30至3.41))的不持续用药率较高。综合未使用过OAC和曾使用过OAC的患者,随访2个月后,利伐沙班的不持续用药率也高于阿哌沙班(风险比1.69(1.19至2.39))。

结论

观察到的OAC处方差异可能导致比较疗效研究中的选择偏倚。持续用药模式随随访时间变化,但在英国有迹象表明阿哌沙班的持续用药率高于其他OAC。需要进行一项随访时间更长的更大规模研究来证实这些发现。本研究已在ClinicalTrials.gov注册(NCT02488421)。

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