艾多沙班或华法林与单一抗血小板治疗在心房颤动患者中的联合使用：ENGAGE AF-TIMI48试验分析

Concomitant Use of Single Antiplatelet Therapy With Edoxaban or Warfarin in Patients With Atrial Fibrillation: Analysis From the ENGAGE AF-TIMI48 Trial.

作者信息

Xu Haiyan, Ruff Christian T, Giugliano Robert P, Murphy Sabina A, Nordio Francesco, Patel Indravadan, Shi Minggao, Mercuri Michele, Antman Elliott M, Braunwald Eugene

机构信息

TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.

Daiichi Sankyo Pharma Development, Edison, NJ.

出版信息

J Am Heart Assoc. 2016 Feb 23;5(2):e002587. doi: 10.1161/JAHA.115.002587.

BACKGROUND

We studied the concomitant use of single antiplatelet therapy (SAPT) on the efficacy and safety of the anti-Xa agent edoxaban in patients with atrial fibrillation (AF).

METHODS AND RESULTS

ENGAGE AF-TIMI 48 was a randomized trial that compared 2 dose regimens of edoxaban with warfarin. We studied both the approved high-dose edoxaban regimen (HDER; 60 mg daily reduced by one half in patients with anticipated increased drug exposure), as well as a lower-dose edoxaban regimen (LDER; 30 mg daily, also reduced by one half in patients with anticipated increased drug regimen). SAPT (aspirin in 92.5%) was administered at the discretion of the treating physician. Cox proportional hazard regressions stratified by SAPT at 3 months with treatment as a covariate were performed. The 4912 patients who received SAPT were more frequently male, with histories of coronary artery disease and diabetes, and had higher CHADS2Vasc and HAS BLED scores than did the 14 977 patients not receiving SAPT. When compared to patients not receiving SAPT, those receiving SAPT had a higher incidence of major bleeding; (adjusted hazard ratio [HRadj]=1.46; 95% CI, 1.27-1.67, P<0.001). SAPT did not alter the relative efficacy of edoxaban compared to warfarin in preventing stroke or systemic embolic events (SEEs): edoxaban versus warfarin without SAPT, hazard ratio (HRadj for HDER)=0.94; (95% CI: 0.77-1.15) with SAPT, HRadj=0.70 (95% CI: 0.50-0.98), P interaction (Pint)=0.14. (HRadj for LDER versus warfarin without SAPT=1.19 (95% CI 0.99-1.43) With SAPT, 1.03 (95% CI, 0.76-1.39) Pint=0.42. Major bleeding was lower with edoxaban than warfarin both without SAPT, HRadj for HDER=0.80 (95% CI, 0.68-0.95), and with SAPT, HRadj=0.82 (95% CI, 0.65-1.03; Pint=0.91). For LDER without SAPT (HRadj=0.56 [95% CI 0.46-0.67]) and with SAPT (HRadj=0.51 [95% CI 0.39-0.66]).

CONCLUSIONS

Patients with AF who were selected by their physicians to receive SAPT in addition to an anticoagulant had a similar risk of stroke/SEE and higher rates of bleeding than those not receiving SAPT. Edoxaban exhibited similar relative efficacy and reduced bleeding compared to warfarin, with or without concomitant SAPT.

CLINICAL TRIAL REGISTRATION

URL: http://www.clinicaltrials.gov/. Unique identifier: NCT00781391.

背景

我们研究了单药抗血小板治疗（SAPT）对房颤（AF）患者使用抗Xa因子药物依度沙班的疗效和安全性的影响。

方法与结果

ENGAGE AF-TIMI 48是一项随机试验，比较了依度沙班的两种剂量方案与华法林。我们研究了批准的高剂量依度沙班方案（HDER；每日60mg，在预期药物暴露增加的患者中减半）以及低剂量依度沙班方案（LDER；每日30mg，在预期药物方案增加的患者中也减半）。SAPT（92.5%为阿司匹林）由治疗医生酌情使用。进行了以3个月时的SAPT分层、治疗作为协变量的Cox比例风险回归分析。接受SAPT的4912例患者比未接受SAPT的14977例患者更常为男性，有冠状动脉疾病和糖尿病病史，且CHADS2Vasc和HAS BLED评分更高。与未接受SAPT的患者相比，接受SAPT的患者大出血发生率更高；（调整后风险比[HRadj]=1.46；95%CI，1.27 - 1.67，P<0.001）。在预防中风或全身性栓塞事件（SEEs）方面，与华法林相比，SAPT并未改变依度沙班的相对疗效：依度沙班与无SAPT的华法林相比，风险比（HDER的HRadj）=0.94；（95%CI：0.77 - 1.15），有SAPT时，HRadj=0.70（95%CI：0.50 - 0.98），交互作用P值（Pint）=0.14。（LDER与无SAPT的华法林相比的HRadj=1.19（95%CI 0.99 - 1.43），有SAPT时为1.03（95%CI，0.76 - 1.39），Pint=0.42。无论有无SAPT，依度沙班的大出血发生率均低于华法林，HDER的HRadj无SAPT时为0.80（95%CI，0.68 - 0.95），有SAPT时为0.82（95%CI，0.65 - 1.03；Pint=0.91）。对于LDER，无SAPT时（HRadj=0.56[95%CI 0.46 - 0.67]），有SAPT时（HRadj=0.51[95%CI 0.39 - 0.66]）。