Collings Shuk-Li, Lefèvre Cinira, Johnson Michelle E, Evans David, Hack Guido, Stynes Gillian, Maguire Andrew
OXON Epidemiology, London, United Kingdom.
Centre for Observational Research and Data Sciences, Bristol-Myers Squibb, Paris, France.
PLoS One. 2017 Oct 10;12(10):e0185642. doi: 10.1371/journal.pone.0185642. eCollection 2017.
This study examined characteristics and treatment persistence among patients prescribed oral anticoagulants (OACs) for stroke prevention in non-valvular atrial fibrillation (NVAF). We identified 15,244 patients (51.8% male, 72.7% aged ≥70) with NVAF and no prior OAC therapy who were prescribed apixaban (n = 1,303), rivaroxaban (n = 5,742), dabigatran (n = 1,622) or vitamin-K antagonists (VKAs, n = 6,577) between 1-Dec-2012 and 31-Oct-2014 in German primary care (IMS® Disease Analyzer). We compared OAC persistence using Cox regression over patients' entire follow-up and using a data-driven time-partitioned approach (before/after 100 days) to handle non-proportional hazards. History of stroke risk factors (stroke/transient ischaemic attack [TIA] 15.2%; thromboembolism 14.1%; hypertension 84.3%) and high bleeding risk (HAS-BLED score≥3 68.4%) was common. Apixaban-prescribed patients had more frequent history of stroke/TIA (19.7%) and high bleeding risk (72.6%) than other OACs. 12-month persistence rates were: VKA 57.5% (95% confidence interval (CI) 56.0-59.0%), rivaroxaban 56.6% (54.9-58.2%), dabigatran 50.1% (47.2-53.1%), apixaban 62.9% (58.8-67.0%). Over entire follow-up, compared to VKA, non-persistence was similar with apixaban (adjusted hazard ratio 1.08, 95% CI 0.95-1.24) but higher with rivaroxaban (1.21, 1.14-1.29) and dabigatran (1.53, 1.40-1.68). Using post-hoc time-partitioned approach: in first 100 days, non-persistence was higher with apixaban (1.37, 1.17-1.59), rivaroxaban (1.41, 1.30-1.53) and dabigatran (1.91, 1.70-2.14) compared to VKA. Compared to apixaban, rivaroxaban non-persistence was similar (1.03, 0.89-1.20), dabigatran was higher (1.39, 1.17-1.66). After 100 days, apixaban non-persistence was lower than VKA (0.66, 0.52-0.85); rivaroxaban (0.97, 0.87-1.07) and dabigatran (1.10, 0.95-1.28) were similar to VKA. Furthermore, rivaroxaban (1.46, 1.13-1.88) and dabigatran (1.67, 1.26-2.19) non-persistence was higher than apixaban. This study describes real-world observations on OAC use, particularly early apixaban use following approval for NVAF, in Germany. We identified potential differential OAC prescribing and higher persistence with apixaban than other OACs after 100 days' treatment. Larger studies are needed with longer follow-up to establish long-term patterns.
本研究调查了非瓣膜性心房颤动（NVAF）患者中接受口服抗凝剂（OAC）预防卒中治疗的患者特征及治疗依从性。我们在德国初级医疗（IMS®疾病分析器）中识别出15244例NVAF患者（男性占51.8%，72.7%年龄≥70岁），这些患者既往未接受过OAC治疗，在2012年12月1日至2014年10月31日期间被处方阿哌沙班（n = 1303）、利伐沙班（n = 5742）、达比加群（n = 1622）或维生素K拮抗剂（VKA，n = 6577）。我们使用Cox回归分析了患者整个随访期间的OAC依从性，并采用数据驱动的时间分割方法（100天前后）来处理非比例风险。卒中危险因素病史（卒中/短暂性脑缺血发作[TIA] 15.2%；血栓栓塞14.1%；高血压84.3%）和高出血风险（HAS - BLED评分≥3 68.4%）很常见。与其他OAC相比，接受阿哌沙班治疗的患者有更频繁的卒中/TIA病史（19.7%）和高出血风险（72.6%）。12个月的依从率分别为：VKA 57.5%（95%置信区间[CI] 56.0 - 59.0%），利伐沙班56.6%（54.9 - 58.2%），达比加群50.1%（47.2 - 53.1%），阿哌沙班62.9%（58.8 - 67.0%）。在整个随访期间，与VKA相比，阿哌沙班的非依从性相似（调整后风险比1.08，95% CI 0.95 - 1.24），但利伐沙班（1.21，1.14 - 1.29）和达比加群（1.53，1.40 - 1.68）的非依从性更高。采用事后时间分割方法：在最初100天内，与VKA相比，阿哌沙班（1.37，1.17 - 1.59）、利伐沙班（1.41，1.30 - 1.53）和达比加群（1.91，1.70 - 2.14）的非依从性更高。与阿哌沙班相比，利伐沙班的非依从性相似（1.03，0.89 - 1.20），达比加群更高（1.39，1.17 - 1.66）。100天后，阿哌沙班的非依从性低于VKA（0.66，0.52 - 0.85）；利伐沙班（0.97，0.87 - 1.07）和达比加群（1.10，0.95 - 1.28）与VKA相似。此外，利伐沙班（1.46，1.13 - 1.88）和达比加群（1.67，1.26 - 2.19）的非依从性高于阿哌沙班。本研究描述了德国OAC使用的真实世界观察结果，特别是NVAF获批后阿哌沙班的早期使用情况。我们发现了OAC处方的潜在差异，且治疗100天后阿哌沙班的依从性高于其他OAC。需要进行更大规模、更长随访时间的研究来确定长期模式。
