EHJ：Betrixaban能降低房颤病人主要不良症状的发生率

房颤病人发生缺血性中风的危险很高。华法林的使用具有挑战性，它通常具有不可预知的抗凝作用，导致出血的危险性高。Betrixaban是一种新型的口服Xa因子抑制剂，它能被快速吸收，3-4小时血药浓度达峰值。Betrixaban已进行2期临床研究。本研究目的是评估Betrixaban的安全性和耐受性。结果显示：Betrixaban能减低主要不良症状的发生率。

患有房颤和多个中风危险因子的病人被随机分为不同剂量（每天40,60,80mg）的betrixaban组或华法林组，调整国际标准化比值为2.0-3.0。主要评价指标是主要或临床相关的非主要出血。平均随访天数是147天。508位病人随机分组，平均CHAD得分是2.2；87%的病人以前接受过维生素K拮抗剂的治疗。华法林治疗范围的时间是63.4%。每天betrixaban 40，60，80 mg 组病人出血数为1，5，5，华法林组为7。主要症状的发生率在40mg betrixaban组最低（相对于华法林组，风险比=0.14，精确分层的log-rank P值为0.04，未经调整的多个测试）。betrixaban 60 或80 mg组，主要症状发生率与华法林组很相似。2例发生缺血性中风，betrixaban 60 和 80 mg 组各1例。2例发生血管性死亡，betrixaban 40 mg和 华法林组各1例。Betrixaban组与华法林组相比，腹泻发生率高。

结论：每日40-80mg的Betrixaban有较好的耐受性，在中风发生方面，与华法林控制较好的房颤病人相比，其出血率相似或更低。结果提示了Betrixaban的剂量范围与出血的关系。

Betrixaban compared with warfarin in patients with atrial fibrillation: results of a phase 2, randomized, dose-ranging study (Explore-Xa)
Aims
Patients with atrial fibrillation (AF) are at increased risk of stroke. Betrixaban is a novel oral factor Xa inhibitor administered once daily, mostly excreted unchanged in the bile and with low (17%) renal excretion.
Methods and results
Patients with AF and more than one risk factor for stroke were randomized to one of three blinded doses of betrixaban (40, 60, or 80 mg once daily) or unblinded warfarin, adjusted to an international normalized ratio of 2.0–3.0. The primary outcome was major or clinically relevant non-major bleeding. The mean follow-up was 147 days. Among 508 patients randomized, the mean CHADS2 score was 2.2; 87% of patients had previously received vitamin K antagonist therapy. The time in therapeutic range on warfarin was 63.4%. There were one, five, five, and seven patients with a primary outcome on betrixaban 40, 60, 80 mg daily, or warfarin, respectively. The rate of the primary outcome was lowest on betrixaban 40 mg (hazard ratio compared with warfarin = 0.14, exact stratified log-rank P-value 0.04, unadjusted for multiple testing). Rates of the primary outcome with betrixaban 60 or 80 mg were more similar to those of wafarin. Two ischaemic strokes occurred, one each on betrixaban 60 and 80 mg daily. There were two vascular deaths, one each on betrixaban 40 mg and warfarin. Betrixaban was associated with higher rates of diarrhoea than warfarin.
Conclusion
Betrixaban was well tolerated and had similar or lower rates of bleeding compared with well-controlled warfarin in patients with AF at risk for stroke.