Umashankar Kandavadivu, Mammi Marco, Badawoud Ebtissam, Tang Yuzhi, Zhou Mengqi, Borges Jorge C, Liew Aaron, Migliore Mattia, Mekary Rania A
School of Pharmacy, Massachusetts College of Pharmacy and Health Sciences (MCPHS) University, Boston, MA, USA.
Neurosurgery Unit, Santa Croce e Carle Hospital, Cuneo, Italy.
Cardiovasc Drugs Ther. 2023 Dec;37(6):1225-1237. doi: 10.1007/s10557-022-07336-w. Epub 2022 Apr 25.
The purpose of this meta-analysis was to compare efficacy and safety of direct oral anticoagulants (DOACs) to warfarin for secondary stroke prevention among adult patients with atrial fibrillation and prior stroke.
Major repositories were screened for randomized controlled trials (RCTs), RCT subgroups, and observational studies (OBSs, divided in claims and non-claims). Occurrences of ischemic stroke or transient ischemic attack, systemic embolism, all-cause mortality, intracranial hemorrhage (ICH), and major bleeding were outcomes of interest. Hazard ratios (HRs) and their confidence intervals (95%CIs) were pooled using random-effects models for each study design. Claims studies were analyzed separately from non-claims, while RCT subgroups were grouped with OBSs (non-claims) as the randomization was broken.
Of 8647 articles, 20 were included (one RCT, six RCT subgroups, nine claims, and four non-claims). Comparing DOACs to warfarin, pooled HRs (95%CI) were consistently in favor of DOACs although some did not reach statistical significance: for ischemic stroke, 0.84 (0.66-1.07) in claims; 0.90 (0.77-1.06) in non-claims and RCT subgroups; for systemic embolism, 0.77 (0.62-0.96) in claims; 0.86 (0.77-0.96) in non-claims and RCT subgroups; for all-cause mortality, 0.57 (0.33-0.99) in claims; 0.87 (0.79-0.96) in non-claims and RCT subgroups; for ICH, 0.72 (0.39-1.33) in claims; 0.51 (0.38-0.67) in non-claims and RCT subgroups; and for major bleeding, 0.86 (0.71-1.03) in claims; 0.90 (0.76-1.08) for non-claims and RCT subgroups.
DOACs were associated with better efficacy and safety profiles than warfarin in atrial fibrillation patients with prior stroke, more specifically a lower risk of systemic embolism, all-cause mortality, and ICH.
本荟萃分析的目的是比较直接口服抗凝剂（DOACs）与华法林在有房颤病史和既往卒中的成年患者二级预防卒中方面的疗效和安全性。
对主要数据库进行筛选，纳入随机对照试验（RCT）、RCT亚组和观察性研究（OBS，分为索赔数据研究和非索赔数据研究）。缺血性卒中或短暂性脑缺血发作、全身性栓塞、全因死亡率、颅内出血（ICH）和大出血的发生率是关注的结局指标。对于每种研究设计，使用随机效应模型汇总风险比（HRs）及其置信区间（95%CI）。索赔数据研究与非索赔数据研究分开分析，而RCT亚组与非索赔数据的OBS归为一组，因为随机分组已被打破。
在8647篇文章中，纳入了20篇（1项RCT、6个RCT亚组、9项索赔数据研究和4项非索赔数据研究）。将DOACs与华法林进行比较，汇总的HRs（95%CI）始终有利于DOACs，尽管有些未达到统计学显著性：对于缺血性卒中，索赔数据研究中为0.84（0.66 - 1.07）；非索赔数据研究和RCT亚组中为0.90（0.77 - 1.06）；对于全身性栓塞，索赔数据研究中为0.77（0.62 - 0.96）；非索赔数据研究和RCT亚组中为0.86（0.77 - 0.96）；对于全因死亡率，索赔数据研究中为0.57（0.33 - 0.�9）；非索赔数据研究和RCT亚组中为0.87（0.79 - 0.96）；对于ICH，索赔数据研究中为0.72（0.39 - 1.33）；非索赔数据研究和RCT亚组中为0.51（0.38 - 0.67）；对于大出血，索赔数据研究中为0.86（0.71 - 1.03）；非索赔数据研究和RCT亚组中为0.90（0.76 - 1.08）。
在有既往卒中的房颤患者中，DOACs与比华法林更好的疗效和安全性相关，更具体地说，全身性栓塞、全因死亡率和ICH的风险更低。
