Larsen Torben Bjerregaard, Gorst-Rasmussen Anders, Rasmussen Lars Hvilsted, Skjøth Flemming, Rosenzweig Mary, Lip Gregory Y H
Department of Cardiology, Atrial Fibrillation Study Group, Aalborg University Hospital, Aalborg, Denmark; Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Faculty of Health, Aalborg University, Aalborg, Denmark.
Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Faculty of Health, Aalborg University, Aalborg, Denmark.
Am J Med. 2014 Jul;127(7):650-656.e5. doi: 10.1016/j.amjmed.2014.01.031. Epub 2014 Feb 13.
The bleeding risk among patients with atrial fibrillation is higher early after initiating therapy with vitamin K antagonists (VKAs). Evidence is limited on how prior VKA experience affects bleeding risk when initiating novel oral anticoagulant therapy. We investigated this among patients with atrial fibrillation initiating dabigatran therapy.
By using nationwide Danish prescription and patient registries, we identified 11,315 first-time dabigatran users with atrial fibrillation. Warfarin controls were matched in a 2:1 ratio according to VKA experience status. The average follow-up time was 13 months. Across the 6 combinations of treatment (dabigatran 110 mg, dabigatran 150 mg, and warfarin) and VKA experience status (naive or experienced), VKA-naïve warfarin initiators had the highest rate of any bleeding event. Cox regressions adjusted for baseline characteristics showed reductions relative to this group ranging from 19% for VKA-experienced dabigatran 110 mg users (hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.66-1.00) to 41% for VKA-experienced dabigatran 150 mg users (HR, 0.59; 95% CI, 0.46-0.75). Among switchers to dabigatran from warfarin, when comparing with warfarin-persisting users, the rate of any bleeding was nonsignificantly decreased for switchers to dabigatran 150 mg (HR, 0.80; 95% CI, 0.62-1.03) but not for switchers to dabigatran 110 mg (HR, 1.12; 95% CI, 0.90-1.41). Results for major bleeding were similar. Crude rates of fatal, intracranial, and gastrointestinal bleeding were low.
VKA-naïve warfarin initiators had the highest overall bleeding rate. We found no evidence of marked excess of overall bleeding events when comparing dabigatran with warfarin users, irrespective of prior VKA experience.
在开始使用维生素K拮抗剂（VKA）治疗的早期，心房颤动患者的出血风险较高。关于既往VKA使用经历在开始新型口服抗凝药治疗时如何影响出血风险的证据有限。我们在开始达比加群治疗的心房颤动患者中对此进行了研究。
通过使用丹麦全国性的处方和患者登记系统，我们确定了11315名首次使用达比加群的心房颤动患者。根据VKA使用经历状态，以2:1的比例匹配华法林对照组。平均随访时间为13个月。在治疗（达比加群110mg、达比加群150mg和华法林）和VKA使用经历状态（初治或有经验）的6种组合中，初治华法林使用者的任何出血事件发生率最高。针对基线特征进行调整的Cox回归显示，相对于该组，有VKA使用经验的达比加群110mg使用者降低了19%（风险比[HR]，0.81；95%置信区间[CI]，0.66 - 1.00），有VKA使用经验的达比加群150mg使用者降低了41%（HR，0.59；95%CI，0.46 - 0.75）。在从华法林转换为达比加群的患者中，与持续使用华法林的患者相比，转换为达比加群150mg的患者任何出血发生率无显著降低（HR，0.80；95%CI，0.62 - 1.03），但转换为达比加群110mg的患者并非如此（HR，1.12；95%CI，0.90 - 1.41）。主要出血的结果相似。致命性、颅内和胃肠道出血的粗发生率较低。
初治华法林使用者的总体出血率最高。我们发现，无论既往VKA使用经历如何，在比较达比加群与华法林使用者时，没有证据表明总体出血事件有明显过量。
