Department of Medicine, McMaster University, Hamilton, ON, Canada.
Department of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
J Thromb Haemost. 2017 Jul;15(7):1322-1333. doi: 10.1111/jth.13701. Epub 2017 May 9.
Essentials The association of body weight and patient-important outcomes remains unknown. Phase III randomized controlled trials of direct oral anticoagulants (DOACs) were searched. Risk of outcomes varying among body weight subgroups is not attributable to anticoagulant type. Dose adjustment of DOACs, outside that recommended, is unlikely to improve the outcomes. Click to hear Dr Braunwald's perspective on antithrombotic therapy in cardiovascular disease SUMMARY: Background Concerns have arisen in direct oral anticoagulant (DOAC)-treated patients about safety and efficacy in extremes of body weight. The aims of this systematic review were to investigate the association of body weight and patient-important outcomes in patients treated with DOACs or warfarin, and to demonstrate the fixed-dose effect of DOACs. Methods MEDLINE and EMBASE were searched until November 2016. Phase III randomized controlled trials (RCTs) using DOACs in atrial fibrillation (AF) and acute venous thromboembolism (VTE) were included. Relative risk and 95% confidence interval were calculated. The pooled estimates were performed using a Mantel-Haenszel random effects model. Results A total of 11 phase III RCTs were included. Low body weight was associated with increased risk of thromboembolism compared with non-low body weight (relative risk [RR], 1.57; 95% confidence interval [CI], 1.34-1.85). High body weight was not associated with risk of thromboembolism compared with non-high body weight (RR, 0.88; 95% CI, 0.63-1.23). The subgroup of AF patients with high body weight had a lower risk of thromboembolism compared with non-high body weight (RR, 0.43; 95% CI, 0.28-0.67). Bleeding outcomes were comparable for all body weight comparisons. There were no clear interactions between types of anticoagulant in all outcomes. Conclusion The pooled effect of both the DOAC and comparison arms was likely to be attributable to differences in baseline thrombotic risk in each body weight category, rather than an effect of the type or dose of DOAC used for each indication. Dose adjustment of DOACs, outside that recommended in the package insert, is unlikely to improve safety or efficacy.
在接受直接口服抗凝剂（DOAC）治疗的患者中，人们对超重和极重患者的安全性和疗效产生了担忧。本系统评价旨在探讨 DOAC 与华法林治疗患者的体重与患者重要结局的相关性，并展示 DOAC 的固定剂量效应。
检索 MEDLINE 和 EMBASE 直至 2016 年 11 月。纳入使用 DOAC 治疗心房颤动（AF）和急性静脉血栓栓塞症（VTE）的 III 期随机对照试验（RCT）。计算相对风险和 95%置信区间。使用 Mantel-Haenszel 随机效应模型进行汇总估计。
共纳入 11 项 III 期 RCT。与非低体重相比，低体重与血栓栓塞风险增加相关（相对风险 [RR]，1.57；95%置信区间 [CI]，1.34-1.85）。与非高体重相比，高体重与血栓栓塞风险无关（RR，0.88；95%CI，0.63-1.23）。AF 患者中高体重亚组的血栓栓塞风险低于非高体重亚组（RR，0.43；95%CI，0.28-0.67）。所有体重比较的出血结局相似。所有结局均未发现抗凝药物类型之间存在明显交互作用。
DOAC 和对照组的汇总效应可能归因于每个体重类别基线血栓形成风险的差异，而不是每种适应证所用 DOAC 的类型或剂量的影响。DOAC 剂量调整，超出说明书推荐范围，不太可能改善安全性或疗效。
