口服抗凝药物在心房颤动合并晚期或终末期肾脏疾病患者中的应用：一项系统评价与荟萃分析。
完整摘要 · 中文译文
背景：患有心房颤动（AF）合并晚期慢性肾脏病（CKD）的患者，其血栓栓塞事件和出血事件的风险均显著升高。虽然口服抗凝治疗是AF患者预防卒中的基石，但在患有4-5期CKD和接受透析的终末期肾病（ESRD）患者中，该治疗的最佳应用方式仍不确定，因为这些人群在很大程度上被排除在确立直接口服抗凝药（DOACs）在普通AF人群中疗效的里程碑式试验之外。本研究旨在系统评估并比较维生素K拮抗剂（VKAs）和DOACs（包括Xa因子抑制剂）与替代抗凝策略或无抗凝治疗相比，在合并晚期CKD（包括非透析依赖的4-5期CKD和透析依赖的ESRD）的AF患者中的疗效和安全性。 方法：对PubMed（MEDLINE）、Cochrane图书馆和ClinicalTrials.gov进行了系统检索，检索时间截至2026年1月30日。纳入评估成人AF合并4-5期CKD（估计肾小球滤过率（eGFR）<30 mL/min/1.73 m2，未接受透析）或透析依赖型ESRD患者口服抗凝治疗效果的随机对照试验和观察性队列研究。关注的结果包括卒中、短暂性脑缺血发作或系统性栓塞的复合终点，大出血（国际血栓与止血学会（ISTH）定义或研究定义），以及全因死亡率。由于临床和方法学上的异质性，大多数比较的证据采用叙述性综合方式进行汇总。 ns; 在依赖透析患者中比较Xa因子抑制剂与维生素K拮抗剂（VKAs）的随机试验被汇总于一项随机效应荟萃分析中。结果：共20项研究符合纳入标准，包括四项随机试验、一项随机对照试验（RCT）（ARISTOTLE）的亚组分析和十五项观察性队列。四项研究评估了未接受透析的晚期慢性肾脏病（CKD）患者，而十六项研究聚焦于透析人群。在非透析4-5期CKD中，直接口服抗凝药（DOAC）治疗，尤其是阿哌沙班，通常与华法林相比具有相当或降低的血栓栓塞风险以及较低的大出血发生率。观察性数据还提示，与未抗凝相比，DOACs可能具有潜在的死亡率获益。相反，在依赖透析的终末期肾病（ESRD）中的发现存在异质性。与未抗凝相比，华法林并未一致地与卒中风险降低相关，并且常与出血风险升高相关。观察性研究提示，与VKAs相比，阿哌沙班可能在维持相似血栓栓塞保护的同时带来较低的大出血风险；然而，随机证据有限且把握度不足，无法证明明确的净临床获益。在对四项透析随机试验（n = 486）的荟萃分析中，Xa因子抑制剂较VKAs与更少的国际血栓与止血学会（ISTH）大出血相关（汇总风险比（RR）0.64，95%置信区间（CI）0.42-0.99；在Mantel-Haenszel或Hartung-Knapp敏感性分析中未保留），在卒中、短暂性脑缺血发作或系统方面无显著差异 栓塞（合并RR 0.46，95% CI 0.20-1.02）或全因死亡率（RR 0.88，95% CI 0.58-1.35）。 结论：在慢性肾脏病的不同分期中，口服抗凝治疗的风险-获益谱存在差异。在不需要透析的4-5期慢性肾脏病中，DOACs在保持疗效的同时，似乎比VKAs提供更有利的安全性特征。在依赖透析的终末期肾病中，抗凝治疗的净临床获益仍不确定，尤其是华法林。需要进一步设计合理、效能充分的随机试验来明确这一高危人群的最佳抗凝策略。在此之前，治疗决策应保持个体化，平衡血栓栓塞与出血风险。 PROSPERO注册号：https://www.crd.york.ac.uk/PROSPERO/view/CRD420261286449。
完整摘要 · 英文原文
BACKGROUND: Patients with atrial fibrillation (AF) and advanced chronic kidney disease (CKD) face a markedly elevated risk of both thromboembolic and bleeding events. While oral anticoagulation is the cornerstone of stroke prevention in AF, the optimal use of this treatment in patients with stage 4-5 CKD and end-stage renal disease (ESRD) undergoing dialysis remains uncertain, as these populations were largely excluded from the landmark trials that established the efficacy of direct oral anticoagulants (DOACs) in the general AF population. This study aimed to systematically evaluate and compare the efficacy and safety of vitamin K antagonists (VKAs) and DOACs, including factor Xa inhibitors, compared with alternative anticoagulation strategies or no anticoagulation in patients with AF and advanced CKD, including both non-dialysis-dependent stage 4-5 CKD and dialysis-dependent ESRD. METHODS: A systematic search of PubMed (MEDLINE), the Cochrane Library, and ClinicalTrials.gov was performed through January 30, 2026. Randomized controlled trials and observational cohort studies evaluating oral anticoagulation in adults with AF and stage 4-5 CKD (estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2, not on dialysis) or ESRD on dialysis were included. Outcomes of interest were a composite of stroke, transient ischemic attack or systemic embolism, major bleeding (International Society on Thrombosis and Haemostasis (ISTH) or study-defined), and all-cause mortality. Owing to clinical and methodological heterogeneity, evidence was synthesized narratively for most comparisons; randomized trials comparing factor Xa inhibitors with VKAs in dialysis-dependent patients were pooled in a random-effects meta-analysis. RESULTS: A total of 20 studies met the inclusion criteria, comprising four randomized trials, one subgroup analysis of an RCT (ARISTOTLE), and fifteen observational cohorts. Four studies evaluated patients with advanced CKD not receiving dialysis, while sixteen focused on dialysis populations. In non-dialysis stage 4-5 CKD, DOAC therapy, particularly apixaban, was generally associated with comparable or reduced thromboembolic risk and lower rates of major bleeding compared with warfarin. Observational data also suggested a potential mortality benefit with DOACs compared with no anticoagulation. In contrast, findings in dialysis-dependent ESRD were heterogeneous. Warfarin was not consistently associated with reduced stroke risk compared with no anticoagulation and was frequently linked to elevated bleeding risk. Observational studies suggest that apixaban may confer a lower risk of major bleeding compared with VKAs while maintaining similar thromboembolic protection; however, randomized evidence has been limited and underpowered to demonstrate a definitive net clinical benefit. In a meta-analysis of the four dialysis randomized trials (n = 486), factor Xa inhibitors were associated with less ISTH major bleeding than VKAs (pooled risk ratio (RR) 0.64, 95% confidence interval (CI) 0.42-0.99; not retained in Mantel-Haenszel or Hartung-Knapp sensitivity analyses), with no significant difference in stroke, transient ischemic attack or systemic embolism (pooled RR 0.46, 95% CI 0.20-1.02) or all-cause mortality (RR 0.88, 95% CI 0.58-1.35). CONCLUSION: The risk-benefit profile of oral anticoagulation differs across the CKD spectrum. In stage 4-5 CKD not requiring dialysis, DOACs appear to offer a more favorable safety profile than VKAs while preserving efficacy. In dialysis-dependent ESRD, the net clinical benefit of anticoagulation remains uncertain, particularly for warfarin. Further adequately powered randomized trials are needed to clarify optimal anticoagulation strategies in this high-risk population. Until then, treatment decisions should remain individualized, balancing thromboembolic and bleeding risk. PROSPERO REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420261286449.