Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA (B.N.).
Division of Cardiology, Staten Island University Hospital-Northwell Health, NY (B.P.).
Circulation. 2018 Oct 2;138(14):1402-1411. doi: 10.1161/CIRCULATIONAHA.117.031457.
Direct oral anticoagulants (DOACs) are surpassing warfarin as the anticoagulant of choice for stroke prevention in nonvalvular atrial fibrillation. DOAC outcomes in elective periprocedural settings have not been well elucidated and remain a source of concern for clinicians. The aim of this meta-analysis was to evaluate the periprocedural safety and efficacy of DOACs versus warfarin in patients with nonvalvular atrial fibrillation.
We reviewed the literature for data from phase III randomized controlled trials comparing DOACs with warfarin in the periprocedural period among patients with nonvalvular atrial fibrillation. Substudies from 4 trials (RE-LY [Randomized Evaluation of Long-Term Anticoagulation Therapy], ROCKET AF [Rivaroxaban Once Daily Oral Direct Factor Xa Inhibitor Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation], ARISTOTLE [Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation], and ENGAGE-AF [Effective Anticoagulation With Factor xA Next Generation in Atrial Fibrillation]) were included in the meta-analysis. DOACs as a group and warfarin were compared in terms of the 30-day pooled risk for stroke/systemic embolism, major bleeding, and death, according to whether the study drug was interrupted or not periprocedurally. The overall relative risk (RR) was estimated with a random-effects model. The I test was used to assess heterogeneity in RR among the studies.
In the uninterrupted anticoagulant strategy, there were no differences in the rates of stroke/systemic embolism (pooled risk, 0.6% [29 events/4519 procedures] versus 1.1% [31/2971]; RR, 0.70; 95% confidence interval [CI], 0.41-1.18) and death (1.4% versus 1.8%; RR, 0.77; 95% CI, 0.53-1.12) between DOACs and warfarin and significantly fewer major bleeding events (2.0% versus 3.3%; RR, 0.62; 95% CI, 0.47-0.82) with DOACs compared to warfarin. Under an interrupted strategy, there was no significant difference between DOACs versus warfarin for stroke/systemic embolism (0.4% [41/9260] versus 0.5% [31/7168]; RR, 0.95; 95% CI, 0.59-1.55), major bleeding (2.1% versus 2.0%; RR, 1.05; 95% CI, 0.85-1.30), and death (0.7% versus 0.6%; RR, 1.24; 95% CI, 0.76-2.04). The studies were homogeneous ( I=0.0%) for all calculated pooled associations except for the RR of death in the interrupted strategy ( I=26.3%).
The short-term safety and efficacy of DOACs and warfarin are not different in patients with nonvalvular atrial fibrillation periprocedurally. Under an uninterrupted anticoagulation strategy, DOACs are associated with a 38% lower risk of major bleeding compared with warfarin.
直接口服抗凝剂（DOAC）在非瓣膜性心房颤动的卒中预防中正在超越华法林成为抗凝的首选。在择期围手术期，DOAC 的结果尚未得到很好的阐明，仍然是临床医生关注的问题。本荟萃分析的目的是评估 DOAC 与华法林在非瓣膜性心房颤动患者围手术期的安全性和有效性。
我们检索了 III 期随机对照试验的数据，这些研究比较了非瓣膜性心房颤动患者围手术期 DOAC 与华法林的疗效。从 4 项试验（RE-LY [长期抗凝治疗随机评价]、ROCKET AF [每日口服利伐沙班与维生素 K 拮抗剂预防心房颤动卒中与栓塞的比较试验]、ARISTOTLE [阿哌沙班预防心房颤动患者卒中]和 ENGAGE-AF [心房颤动中新一代 Xa 因子抑制剂的有效抗凝])的亚研究中纳入了荟萃分析。根据研究药物是否在围手术期中断，将 DOAC 作为一个整体与华法林进行比较，30 天内卒中/全身性栓塞、大出血和死亡的风险。采用随机效应模型估计总体相对风险（RR）。采用 I 检验评估研究间 RR 的异质性。
在未中断抗凝策略中，DOAC 与华法林之间卒中/全身性栓塞（累积风险，0.6%[4519 例/29 例]与 1.1%[2971 例/31 例]；RR，0.70；95%置信区间[CI]，0.41-1.18）和死亡（1.4%与 1.8%；RR，0.77；95% CI，0.53-1.12）的发生率无差异，而 DOAC 组的大出血事件（2.0%与 3.3%；RR，0.62；95% CI，0.47-0.82）明显少于华法林组。在中断抗凝策略下，DOAC 与华法林相比，卒中/全身性栓塞（0.4%[9260 例/41 例]与 0.5%[7168 例/31 例]；RR，0.95；95% CI，0.59-1.55）、大出血（2.1%与 2.0%；RR，1.05；95% CI，0.85-1.30）和死亡（0.7%与 0.6%；RR，1.24；95% CI，0.76-2.04）之间无显著差异。除了中断抗凝策略下的死亡率 RR（I=26.3%）外，所有计算的合并关联的研究均同质（I=0.0%）。
非瓣膜性心房颤动患者围手术期 DOAC 和华法林的短期安全性和有效性无差异。在未中断抗凝策略下，与华法林相比，DOAC 可降低 38%的大出血风险。
