Department of Neurology, University Hospital Essen, Essen, Germany.
Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, ON, Canada.
Lancet Neurol. 2010 Dec;9(12):1157-1163. doi: 10.1016/S1474-4422(10)70274-X. Epub 2010 Nov 6.
In the Randomised Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial, dabigatran reduced occurrence of both stroke and haemorrhage compared with warfarin in patients who had atrial fibrillation and were at increased risk of stroke. We aimed to assess the effects of dabigatran compared with warfarin in the subgroup of patients with previous stroke or transient ischaemic attack.
In the RE-LY trial, 18,113 patients from 967 centres in 44 countries were randomly assigned to 110 mg or 150 mg dabigatran twice daily or to warfarin dose adjusted to international normalised ratio 2·0 to 3·0. Median follow-up was 2·0 years (IQR 1·14-2·86), and the primary outcome was stroke or systemic embolism. The primary safety outcome was major haemorrhage. Patients and investigators were aware of whether patients received warfarin or dabigatran, but not of dabigatran dose, and event adjudicators were masked to treatment. In a predefined analysis, we investigated the outcomes of the RE-LY trial in subgroups of patients with or without previous stroke or transient ischaemic attack. RE-LY is registered with ClinicalTrials.gov, NCT00262600.
Within the subgroup of patients with previous stroke or transient ischaemic attack, 1195 patients were from the 110 mg dabigatran group, 1233 from the 150 mg dabigatran group, and 1195 from the warfarin group. Stroke or systemic embolism occurred in 65 patients (2·78% per year) on warfarin compared with 55 (2·32% per year) on 110 mg dabigatran (relative risk 0·84, 95% CI 0·58-1·20) and 51 (2·07% per year) on 150 mg dabigatran (0·75, 0·52-1·08). The rate of major bleeding was significantly lower in patients on 110 mg dabigatran (RR 0·66, 95% CI 0·48-0·90) and similar in those on 150 mg dabigatran (RR 1·01; 95% CI 0·77-1·34) compared with those on warfarin. The effects of both doses of dabigatran compared with warfarin were not significantly different between patients with previous stroke or transient ischaemic attack and those without for any of the outcomes from RE-LY apart from vascular death (110 mg group compared with warfarin group, interaction p=0·038).
The effects of 110 mg dabigatran and 150 mg dabigatran twice daily in patients with previous stroke or transient ischaemic attack are consistent with those of other patients in RE-LY, for whom, compared with warfarin, 150 mg dabigatran reduced stroke or systemic embolism and 110 mg dabligatran was non-inferior. [corrected] Most effects of both dabigatran doses were consistent in patients with versus those without previous stroke or transient ischaemic attack.
Boehringer Ingelheim.
在随机评估长期抗凝治疗试验（RE-LY 试验）中，与华法林相比，达比加群降低了伴有心房颤动且有更高卒中风险的患者发生卒中及出血的风险。我们旨在评估与华法林相比，达比加群在有既往卒中或短暂性脑缺血发作史的亚组患者中的作用。
在 RE-LY 试验中，来自 44 个国家的 967 个中心的 18113 例患者被随机分配至 110mg 或 150mg 达比加群每日两次或调整至国际标准化比值 2.0-3.0 的华法林治疗。中位随访时间为 2.0 年（IQR 1.14-2.86），主要终点为卒中和全身性栓塞。主要安全性结局为大出血。患者和研究者知晓患者接受的是华法林或达比加群治疗，但不了解达比加群的剂量，且事件裁决者对治疗情况设盲。在预先设定的分析中，我们在有或无既往卒中和短暂性脑缺血发作史的患者亚组中调查了 RE-LY 试验的结局。RE-LY 在 ClinicalTrials.gov 注册，NCT00262600。
在有既往卒中和短暂性脑缺血发作史的亚组患者中，110mg 达比加群组有 1195 例患者，150mg 达比加群组有 1233 例患者，华法林组有 1195 例患者。华法林组发生卒中或全身性栓塞 65 例（每年 2.78%），而 110mg 达比加群组为 55 例（每年 2.32%）（RR 0.84，95%CI 0.58-1.20），150mg 达比加群组为 51 例（每年 2.07%）（RR 0.75，0.52-1.08）。110mg 达比加群组大出血发生率显著低于华法林组（RR 0.66，95%CI 0.48-0.90），与华法林组相似（RR 1.01；95%CI 0.77-1.34），而 150mg 达比加群组的发生率与华法林组无显著差异。除血管性死亡外（110mg 组与华法林组，交互 P=0.038），与华法林相比，两种剂量的达比加群在有既往卒中和短暂性脑缺血发作史与无既往卒中和短暂性脑缺血发作史的患者中的作用无显著差异。
与其他 RE-LY 患者相比，110mg 和 150mg 达比加群每日两次在有既往卒中和短暂性脑缺血发作史的患者中的作用与其他患者一致，与华法林相比，150mg 达比加群降低了卒中或全身性栓塞风险，而 110mg 达比加群无显著差异。两种达比加群剂量的大多数作用在有既往卒中和短暂性脑缺血发作史与无既往卒中和短暂性脑缺血发作史的患者中一致。
勃林格殷格翰。
