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.
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【Concomitant Use of Single Antiplatelet Therapy With Edoxaban or Warfarin in Patients With Atrial Fibrillation: Analysis From the ENGAGE AF-TIMI48 Trial.].
【心房纤颤患者单抗血小板治疗与埃多沙班或华法林同时使用：来自ENGAGE AF-TIMI48试验的分析。】
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DOI：10.1161/JAHA.115.002587文章类型：杂志文章
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背景：我们研究了单一抗血小板治疗（SAPT）在抗Xa药物edoxaban对房颤（AF）患者的疗效和安全性中的同时使用。
方法和结果：参与AF-TIMI 48是一项随机试验，比较了edoxaban与华法林的两种剂量方案。我们研究了批准的大剂量edoxaban方案（HDER；预期药物暴露量增加的患者每天60 mg减少一半），以及低剂量的edoxaban方案（LDER；每天30 mg，也减少一半）预期药物治疗增加的患者）。 SAPT（阿司匹林占92.5％）由主治医师酌情服用。在治疗为协变量的情况下，进行了3个月SAPT分层的Cox比例风险回归分析。与未接受SAPT的14 977例患者相比，接受SAPT的4912例患者更为男性，有冠心病和糖尿病病史，并且CHADS2Vasc和HAS BLED评分更高。与未接受SAPT的患者相比，接受SAPT的患者发生大出血的几率更高； （调整后的危险比[HRadj] = 1.46； 95％CI，1.27-1.67，P <0.001）。与华法林相比，SAPT在预防中风或全身性栓塞事件（SEEs）中没有改变edoxaban的相对疗效：edoxaban与没有SAPT的华法林相比，危险比（HDER的HRadj）= 0.94； （95％CI：0.77-1.15）和SAPT，HRadj = 0.70（95％CI：0.50-0.98），P相互作用（Pint）= 0.14。 （对于LDER的HRadj与未使用SAPT的华法林相比，华法林= 1.19（95％CI 0.99-1.43）在使用SAPT时，1.03（95％CI，0.76-1.39）Pint = 0.42。 = 0.80（95％CI，0.68-0.95）和使用SAPT时，HRadj = 0.82（95％CI，0.65-1.03; Pint = 0.91）。对于不使用SAPT的LDER（HRadj = 0.56 [95％CI 0.46-0.67]）并使用SAPT（HRadj = 0.51 [95％CI 0.39-0.66]）。
结论：除抗凝剂外，由医生选择接受房颤治疗的房颤患者与未接受房颤治疗的患者相比，发生中风/ SEE的风险和出血率更高。与华法林相比，在有或没有SAPT的情况下，依多沙班表现出相似的相对疗效并减少了出血。
临床试验注册：URL：http://www.clinicaltrials.gov/。唯一标识符：NCT00781391。
方法和结果：参与AF-TIMI 48是一项随机试验，比较了edoxaban与华法林的两种剂量方案。我们研究了批准的大剂量edoxaban方案（HDER；预期药物暴露量增加的患者每天60 mg减少一半），以及低剂量的edoxaban方案（LDER；每天30 mg，也减少一半）预期药物治疗增加的患者）。 SAPT（阿司匹林占92.5％）由主治医师酌情服用。在治疗为协变量的情况下，进行了3个月SAPT分层的Cox比例风险回归分析。与未接受SAPT的14 977例患者相比，接受SAPT的4912例患者更为男性，有冠心病和糖尿病病史，并且CHADS2Vasc和HAS BLED评分更高。与未接受SAPT的患者相比，接受SAPT的患者发生大出血的几率更高； （调整后的危险比[HRadj] = 1.46； 95％CI，1.27-1.67，P <0.001）。与华法林相比，SAPT在预防中风或全身性栓塞事件（SEEs）中没有改变edoxaban的相对疗效：edoxaban与没有SAPT的华法林相比，危险比（HDER的HRadj）= 0.94； （95％CI：0.77-1.15）和SAPT，HRadj = 0.70（95％CI：0.50-0.98），P相互作用（Pint）= 0.14。 （对于LDER的HRadj与未使用SAPT的华法林相比，华法林= 1.19（95％CI 0.99-1.43）在使用SAPT时，1.03（95％CI，0.76-1.39）Pint = 0.42。 = 0.80（95％CI，0.68-0.95）和使用SAPT时，HRadj = 0.82（95％CI，0.65-1.03; Pint = 0.91）。对于不使用SAPT的LDER（HRadj = 0.56 [95％CI 0.46-0.67]）并使用SAPT（HRadj = 0.51 [95％CI 0.39-0.66]）。
结论：除抗凝剂外，由医生选择接受房颤治疗的房颤患者与未接受房颤治疗的患者相比，发生中风/ SEE的风险和出血率更高。与华法林相比，在有或没有SAPT的情况下，依多沙班表现出相似的相对疗效并减少了出血。
临床试验注册：URL：http://www.clinicaltrials.gov/。唯一标识符：NCT00781391。
