■老年房颤患者服用抗凝药预防中风,与年轻患者相比,出血增加,因此,尽管随机数据有限,但临床医师对老年患者的处方剂量经常低于推荐剂量.
评估80岁及以上房颤患者接受依度沙班治疗的缺血和出血结局,60毫克vs30毫克,和edoxaban,30毫克vs华法林。
■ENGAGEAF-TIMI48试验(在心房颤动-心肌梗死溶栓治疗中使用下一代因子Xa有效抗凝治疗48)是平行设计,双盲,将房颤患者随机分配至2种依度沙班给药方案或华法林之一的全球临床试验。这项次要分析的重点是80岁或80岁以上无剂量减量标准的患者,60毫克vs30毫克,以及有或没有剂量减少标准的患者接受edoxaban,30毫克,vs华法林。研究数据在2022年10月至2023年12月之间进行了分析。
■口服依度沙班,每天一次30毫克;依度沙班,每天一次60毫克;或华法林。
■死亡的主要净临床结果,中风或全身性栓塞,大出血和每个单独的组成部分。
■当前的分析包括2966名80岁及以上的患者(平均[SD]年龄,83[2.7]岁;1671名男性[56%])。在1138名80岁及以上无剂量减量标准的患者中,那些接受edoxaban的人,60毫克vs30毫克,有更多的主要出血事件(风险比[HR],1.57;95%CI,1.04-2.38;P=0.03),尤其是胃肠道出血(HR,2.24;95%CI,1.29-3.90;P=.004),疗效终点无显著差异。研究结果得到了内源性因子Xa抑制分析的支持,抗凝血作用的标志,与接受edoxaban的年轻患者相比,60mg,和接受edoxaban的老年患者,30毫克。在2406名80岁及以上有或没有剂量减少标准的患者中,接受edoxaban的病人,30毫克,与华法林相比,主要净临床结局的发生率较低(HR,0.78;95%CI,0.68-0.91;P=.001),大出血(HR,0.59;95%CI,0.45-0.77;P<.001),和死亡(HR,0.83;95%CI,0.70-1.00;P=0.046),而卒中或全身性栓塞的发生率相当.
■在对ENGAGEAF-TIMI48随机临床试验的事后分析中,80岁及以上的房颤患者,随机接受edoxaban的患者发生严重出血事件较低,每天30毫克,与edoxaban相比,每天60毫克(在没有剂量减少标准的患者中),或华法林(不考虑剂量减少状态),而不会抵消缺血事件的增加。这些数据支持低剂量抗凝剂的概念,比如edoxaban,30毫克,即使在没有减量标准的情况下,老年房颤患者也可考虑使用.
■ClinicalTrials.gov标识符:NCT00781391。
UNASSIGNED: In older patients with atrial fibrillation who take anticoagulants for stroke prevention, bleeding is increased compared with younger patients, thus, clinicians frequently prescribe lower than recommended doses in older patients despite limited randomized data.
UNASSIGNED: To evaluate ischemic and bleeding outcomes in patients 80 years and older with atrial fibrillation receiving edoxaban, 60 mg vs 30 mg, and edoxaban, 30 mg vs warfarin.
UNASSIGNED: The ENGAGE AF-TIMI 48 trial (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) was a parallel-design, double-blind, global clinical trial that randomized patients with atrial fibrillation to either one of 2 edoxaban dosing regimens or warfarin. This secondary analysis focused on patients 80 years or older without dose-reduction criteria receiving edoxaban, 60 mg vs 30 mg, as well as patients with or without dose-reduction criteria receiving edoxaban, 30 mg, vs warfarin. Study data were analyzed between October 2022 and December 2023.
UNASSIGNED: Oral edoxaban, 30 mg once daily; edoxaban, 60 mg once daily; or warfarin.
UNASSIGNED: Primary net clinical outcome of death, stroke or systemic embolism, and major bleeding and each individual component.
UNASSIGNED: The current analysis included 2966 patients 80 years and older (mean [SD] age, 83 [2.7] years; 1671 male [56%]). Among 1138 patients 80 years and older without dose-reduction criteria, those receiving edoxaban, 60 mg vs 30 mg, had more major bleeding events (hazard ratio [HR], 1.57; 95% CI, 1.04-2.38; P = .03), particularly gastrointestinal hemorrhage (HR, 2.24; 95% CI, 1.29-3.90; P = .004), with no significant difference in efficacy end points. Findings were supported by analyses of endogenous factor Xa inhibition, a marker of anticoagulant effect, which was comparable between younger patients receiving edoxaban, 60 mg, and older patients receiving edoxaban, 30 mg. In 2406 patients 80 years and older with or without dose-reduction criteria, patients receiving edoxaban, 30 mg, vs warfarin had lower rates of the primary net clinical outcome (HR, 0.78; 95% CI, 0.68-0.91; P = .001), major bleeding (HR, 0.59; 95% CI, 0.45-0.77; P < .001), and death (HR, 0.83; 95% CI, 0.70-1.00; P = .046), whereas rates of stroke or systemic embolism were comparable.
UNASSIGNED: In this post hoc analysis of the ENGAGE AF-TIMI 48 randomized clinical trial, in patients 80 years and older with atrial fibrillation, major bleeding events were lower in patients randomized to receive edoxaban, 30 mg per day, compared with either edoxaban, 60 mg per day (in patients without dose-reduction criteria), or warfarin (irrespective of dose-reduction status), without an offsetting increase in ischemic events. These data support the concept that lower-dose anticoagulants, such as edoxaban, 30 mg, may be considered in older patients with atrial fibrillation even in the absence of dose-reduction criteria.
UNASSIGNED: ClinicalTrials.gov Identifier: NCT00781391.