Yang Zhenzhen, Wang Jieya, Yuan Ye, Cheng Tian, Ren Feifei, Wang Songsong, Zhang Zhiqing
Department of Pharmacy, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
Department of Pharmacy, The Sixth Affiliated Hospital of Kunming Medical University, Yuxi, China.
Front Cardiovasc Med. 2023 Feb 7;10:1021959. doi: 10.3389/fcvm.2023.1021959. eCollection 2023.
Nowadays, the number of patients with non-valvular atrial fibrillation (NVAF) complicated by end-stage renal disease (ESKD) is increasing. There are significant challenges in anticoagulation with prescription drugs because of the high risk of bleeding and embolism among these patients. However, no randomized controlled trials (RCTs) of warfarin in combination with any non-vitamin K oral anticoagulant (NOACs) have been performed in patients with baseline creatinine clearance (CrCl) <25 ml/min, which makes it difficult to justify the use of anticoagulants in such patients. Then, we aimed to collect and summarize all evidence to enable the anticoagulation of rivaroxaban, which is less cleared by the kidneys, in patients with severe renal insufficiency and to complement and improve the evidence on the use of rivaroxaban for anticoagulation.
The present systematic review and meta-analysis searched the databases of , , the , , , and for relevant studies from inception to 1 June 2022, with the restriction of English and Chinese. Eligible cohort studies and RCTs that reported efficacy outcomes [composite of stroke and systemic embolism (SSE), ischemic stroke (ICS), and systemic embolization] or safety outcomes [major bleeding, intracranial hemorrhage (ICH), and gastrointestinal bleeding (GIB)] of rivaroxaban in NVAF patients with ESKD were enrolled. Two authors completed the data extraction and quality assessment work, respectively. The Cochrane Collaboration tool for assessing the risk of bias was used for RCTs, and the NEW-Castle Ottawa scale was used for study quality assessment for cohort studies. Dichotomous variables were calculated as risk factors with 95% confidence intervals (CIs), and meta-analysis was performed to probe the effect of research design, rivaroxaban dose, and controlled drug factors on outcomes.
In total, three studies were included for meta-analysis, involving 6,071 NVAF patients with ESKD, and two studies were included for qualitative analysis. All included studies were at low risk of bias. A meta-analysis demonstrated that mix-dose rivaroxaban caused no statistical discrepancy in the occurrence of thrombotic and bleeding events when compared to the control group (embolism, LogOR: -0.64, 95% CI: -1.05 to -0.23, P:0.25; bleeding, LogOR: -0.33, 95% CI: -0.63 to -0.03, P:0.15), and low-dose rivaroxaban produced similar results (embolism, LogOR: -1.04, 95% CI: -2.15 to 0.07, P:0.61; bleeding, LogOR: -0.81, 95% CI: -1.19 to -0.44, P:0.93).
In this study, low-dose rivaroxaban (10 mg, once a day) may benefit more than warfarin in patients with NVAF and ESKD.
https://www.crd.york.ac.uk/prospero/#recordDetails, identifier CRD42022330973.
如今，非瓣膜性心房颤动（NVAF）合并终末期肾病（ESKD）的患者数量正在增加。由于这些患者出血和栓塞风险高，使用处方药进行抗凝存在重大挑战。然而，尚未对基线肌酐清除率（CrCl）<25 ml/min的患者进行华法林联合任何非维生素K口服抗凝剂（NOACs）的随机对照试验（RCTs），这使得在此类患者中使用抗凝剂的合理性难以确定。因此，我们旨在收集和总结所有证据，以支持在严重肾功能不全患者中使用肾脏清除率较低的利伐沙班进行抗凝，并补充和完善利伐沙班用于抗凝的证据。
本系统评价和荟萃分析检索了截至2022年6月1日的 、 、 、 、 和 的数据库，限定语言为英文和中文。纳入报告利伐沙班在ESKD合并NVAF患者中的疗效结局[卒中与全身性栓塞（SSE）、缺血性卒中（ICS）和全身性栓塞的复合结局]或安全性结局[大出血、颅内出血（ICH）和胃肠道出血（GIB）]的合格队列研究和RCTs。两位作者分别完成数据提取和质量评估工作。RCTs使用Cochrane协作组的偏倚风险评估工具，队列研究使用纽卡斯尔-渥太华量表进行研究质量评估。二分类变量计算为具有95%置信区间（CIs）的危险因素，并进行荟萃分析以探究研究设计、利伐沙班剂量和对照药物因素对结局的影响。
总共纳入三项研究进行荟萃分析，涉及6071例ESKD合并NVAF患者，两项研究纳入定性分析。所有纳入研究的偏倚风险均较低。荟萃分析表明，与对照组相比，混合剂量利伐沙班在血栓形成和出血事件的发生上无统计学差异（栓塞，LogOR：-0.64，95%CI：-1.05至-0.23，P：0.25；出血，LogOR：-0.33，95%CI：-0.63至-0.03，P：0.15），低剂量利伐沙班产生类似结果（栓塞，LogOR：-1.04，95%CI：-2.15至0.07，P：0.61；出血，LogOR：-0.81，95%CI：-1.19至-0.44，P：0.93）。
在本研究中，低剂量利伐沙班（10 mg，每日一次）在NVAF和ESKD患者中可能比利伐沙班更有益。
https://www.crd.york.ac.uk/prospero/#recordDetails，标识符CRD42022330973。
