Duke Clinical Research Institute, Duke Health, Durham, North Carolina.
Amsterdam UMC Universiteit van Amsterdam, Amsterdam Public Health, Academisch Medisch Centrum, Amsterdam, the Netherlands.
JAMA Cardiol. 2019 Aug 1;4(8):747-755. doi: 10.1001/jamacardio.2019.1880.
The antithrombotic treatment of patients with atrial fibrillation (AF) and coronary artery disease, in particular with acute coronary syndrome (ACS) and/or percutaneous coronary intervention (PCI), poses a significant treatment dilemma in clinical practice.
To study the safety and efficacy of different antithrombotic regimens using a network meta-analysis of randomized controlled trials in this population.
PubMed, EMBASE, EBSCO, and Cochrane databases were searched to identify randomized controlled trials comparing antithrombotic regimens.
Four randomized studies were included (n = 10 026; WOEST, PIONEER AF-PCI, RE-DUAL PCI, and AUGUSTUS).
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used in this systematic review and network meta-analysis between 4 regimens using a Bayesian random-effects model. A pre hoc statistical analysis plan was written, and the review protocol was registered at PROSPERO. Data were analyzed between November 2018 and February 2019.
The primary safety outcome was Thrombolysis in Myocardial Infarction (TIMI) major bleeding; secondary safety outcomes were combined TIMI major and minor bleeding, trial-defined primary bleeding events, intracranial hemorrhage, and hospitalization. The primary efficacy outcome was trial-defined major adverse cardiovascular events (MACE); secondary efficacy outcomes were individual components of MACE.
The overall prevalence of ACS varied from 28% to 61%. The mean age ranged from 70 to 72 years; 20% to 29% of the trial population were women; and most patients were at high risk for thromboembolic and bleeding events. Compared with a regimen of vitamin K antagonist (VKA) plus dual antiplatelet therapy (DAPT; P2Y12 inhibitor plus aspirin), the odds ratios (ORs) for TIMI major bleeding were 0.58 (95% CI, 0.31-1.08) for VKA plus P2Y12 inhibitor, 0.49 (95% CI, 0.30-0.82) for non-VKA oral anticoagulant (NOAC) plus P2Y12 inhibitor, and 0.70 (95% CI, 0.38-1.23) for NOAC plus DAPT. Compared with VKA plus DAPT, the ORs for MACE were 0.96 (95% CI, 0.60-1.46) for VKA plus P2Y12 inhibitor, 1.02 (95% CI, 0.71-1.47) for NOAC plus P2Y12 inhibitor, and 0.94 (95% CI, 0.60-1.45) for NOAC plus DAPT.
A regimen of NOACs plus P2Y12 inhibitor was associated with less bleeding compared with VKAs plus DAPT. Strategies omitting aspirin caused less bleeding, including intracranial bleeding, without significant difference in MACE, compared with strategies including aspirin. Our results support the use of NOAC plus P2Y12 inhibitor as the preferred regimen post-percutaneous coronary intervention for these high-risk patients with AF. A regimen of VKA plus DAPT should generally be avoided.
房颤（AF）合并冠状动脉疾病（尤其是急性冠状动脉综合征[ACS]和/或经皮冠状动脉介入治疗[PCI]）患者的抗栓治疗在临床实践中存在显著的治疗困境。
通过对随机对照试验的网络荟萃分析，研究该人群中不同抗栓方案的安全性和疗效。
通过 PubMed、EMBASE、EBSCO 和 Cochrane 数据库检索比较抗栓方案的随机对照试验。
纳入 4 项随机研究（n=10026；WOEST、PIONEER AF-PCI、RE-DUAL PCI 和 AUGUSTUS）。
本系统评价和网络荟萃分析使用贝叶斯随机效应模型，对 4 种方案进行了 1 次荟萃分析。预先制定了统计分析计划，并在 PROSPERO 上注册了研究方案。数据于 2018 年 11 月至 2019 年 2 月进行分析。
主要安全性结局是心肌梗死溶栓治疗（TIMI）大出血；次要安全性结局是联合 TIMI 大出血和小出血、试验定义的主要出血事件、颅内出血和住院治疗。主要疗效结局是试验定义的主要不良心血管事件（MACE）；次要疗效结局是 MACE 的各个组成部分。
ACS 的总体患病率为 28%61%。平均年龄为 7072 岁；20%29%的试验人群为女性；大多数患者存在血栓栓塞和出血事件的高风险。与维生素 K 拮抗剂（VKA）加双联抗血小板治疗（DAPT；P2Y12 抑制剂加阿司匹林）相比，VKA 加 P2Y12 抑制剂的 TIMI 大出血比值比（OR）为 0.58（95%CI，0.311.08），非 VKA 口服抗凝剂（NOAC）加 P2Y12 抑制剂为 0.49（95%CI，0.300.82），NOAC 加 DAPT 为 0.70（95%CI，0.381.23）。与 VKA 加 DAPT 相比，VKA 加 P2Y12 抑制剂的 MACE OR 为 0.96（95%CI，0.601.46），NOAC 加 P2Y12 抑制剂为 1.02（95%CI，0.711.47），NOAC 加 DAPT 为 0.94（95%CI，0.60~1.45）。
NOAC 加 P2Y12 抑制剂方案与 VKAs 加 DAPT 相比出血较少。与包括阿司匹林的方案相比，不包括阿司匹林的方案（包括颅内出血）出血更少，且 MACE 无显著差异。我们的结果支持在这些高风险 AF 合并 PCI 的患者中使用 NOAC 加 P2Y12 抑制剂作为首选方案。一般应避免 VKA 加 DAPT 方案。
