Johnson Michelle E, Lefèvre Cinira, Collings Shuk-Li, Evans David, Kloss Sebastian, Ridha Essra, Maguire Andrew
OXON Epidemiology, London, UK.
Department of Worldwide Health Economics & Outcomes Research, Bristol-Myers Squibb, Paris, France.
BMJ Open. 2016 Sep 26;6(9):e011471. doi: 10.1136/bmjopen-2016-011471.
To examine the characteristics and persistence in patients newly initiated with oral anticoagulants (OACs) for stroke prevention in non-valvular atrial fibrillation (NVAF).
Cohort study in Clinical Practice Research Datalink.
UK primary care.
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.
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.
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)).
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).
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。
临床实践研究数据链中的队列研究。
英国初级医疗保健机构。
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。
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。
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））。
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）。
