Department of Cardiology, St Antonius Hospital, Nieuwegein, the Netherlands (N.B., A.J.W.M.d.V., B.K.M., J.M.t.B.).
Heart Center, University of Leipzig, Germany (K.B.).
Circulation. 2018 Mar 13;137(11):1117-1129. doi: 10.1161/CIRCULATIONAHA.117.028513. Epub 2017 Nov 3.
Current guidelines recommend non-vitamin K antagonist oral anticoagulants (NOACs) as the first-choice therapy in patients with nonvalvular atrial fibrillation because these drugs have several benefits over the vitamin K antagonists (VKAs). It is unknown whether these benefits remain when NOACs have to be combined with aspirin therapy. To assess the efficacy and safety of NOACs compared with VKAs in patients with atrial fibrillation and concomitant aspirin therapy, we conducted a systematic review and study-based meta-analysis of published randomized controlled trials.
A systematic electronic literature search was done in MEDLINE, EMBASE, and Cochrane CENTRAL Register of Controlled Trials for studies including published data of patients ≥18 years of age with nonvalvular atrial fibrillation, randomized to either VKAs or NOACs, or receiving aspirin therapy at any time during the study that report all-cause stroke or systemic embolism, vascular death, myocardial infarction, major bleeding, or intracranial hemorrhage as an outcome. Hazard ratios (HRs) with 95% confidence intervals (CIs) for each outcome were extracted from the individual studies and pooled with random-effects meta-analysis.
This study-based meta-analysis was restricted to the subgroups of patients on aspirin therapy (n=21 722) from 4 randomized controlled trials comparing VKAs and NOACs (n=71 681) in nonvalvular atrial fibrillation. In this meta-analysis including patients on mainly low-dose aspirin, NOACs were found to be more effective (outcome of stroke or systemic embolism: HR, 0.78; 95% CI, 0.67-0.91; vascular death: HR, 0.85; 95% CI, 0.76-0.93) and as safe as VKAs with respect to major bleeding (HR, 0.83; 95% CI, 0.69-1.01). NOACs were safer with respect to the reduction of intracranial hemorrhage (HR, 0.38; 95% CI, 0.26-0.56).
This study-based meta-analysis shows that it may be both safer and more effective to use NOACs compared with VKAs to treat patients with nonvalvular atrial fibrillation and concomitant aspirin therapy.
目前的指南建议将非维生素 K 拮抗剂口服抗凝剂（NOACs）作为非瓣膜性心房颤动患者的首选治疗药物，因为这些药物相对于维生素 K 拮抗剂（VKAs）具有多项优势。但当需要将 NOAC 与阿司匹林治疗联合使用时，这些优势是否仍然存在尚不清楚。为了评估与 VKAs 相比，NOAC 在伴有阿司匹林治疗的心房颤动患者中的疗效和安全性，我们对已发表的随机对照试验进行了系统综述和基于研究的荟萃分析。
我们在 MEDLINE、EMBASE 和 Cochrane 对照试验中心注册库中进行了系统的电子文献检索，纳入了包含≥18 岁非瓣膜性心房颤动患者的已发表数据的研究，这些患者被随机分配至 VKAs 或 NOAC 组，或在研究期间的任何时间接受阿司匹林治疗，并报告全因卒中和全身性栓塞、血管性死亡、心肌梗死、大出血或颅内出血等结局。从各个研究中提取每个结局的风险比（HR）及其 95%置信区间（CI），并采用随机效应荟萃分析进行汇总。
这项基于研究的荟萃分析仅限于来自 4 项比较 VKAs 和 NOACs（n=71681）的非瓣膜性心房颤动患者亚组（n=21722），这些患者正在接受阿司匹林治疗。在这项包括主要使用低剂量阿司匹林的患者的荟萃分析中，NOAC 被发现比 VKAs 更有效（卒中和全身性栓塞的结局：HR，0.78；95%CI，0.67-0.91；血管性死亡：HR，0.85；95%CI，0.76-0.93），并且在大出血方面与 VKAs 一样安全（HR，0.83；95%CI，0.69-1.01）。NOAC 在降低颅内出血方面更为安全（HR，0.38；95%CI，0.26-0.56）。
这项基于研究的荟萃分析表明，与 VKAs 相比，在治疗伴有阿司匹林治疗的非瓣膜性心房颤动患者时，NOAC 可能更安全且更有效。
