Table1_Benefits and Harms of Low-Dose Rivaroxaban in Asian Patients With Atrial Fibrillation: A Systematic Review and Meta-analysis of Real-World Studies.docx

Background: Low-dose prescription of rivaroxaban was common among patients with atrial fibrillation (AF) in Asia. However, the benefits and harms of rivaroxaban at a low dosage in Asian patients with AF remains unclear. Accordingly, we aimed to collect and summarize all available evidence to fill this important knowledge gap.Methods: In this systematic review and meta-analysis, we systematically searched databases of MEDLINE, EMBASE, and Cochrane Library for relevant studies from inception until February 23, 2021. Eligible retrospective nationwide or health insurance database studies or prospective registration studies that reported efficacy (stroke/systemic embolism), safety (major bleeding, intracranial hemorrhage, gastrointestinal bleeding), or other outcomes (myocardial infarction, death) of low-dose rivaroxaban in comparison with warfarin in AF patients were enrolled. Data extraction and study quality assessment were conducted by two authors independently. Low dosing of rivaroxaban (15/10 mg) was defined as the received dose lower than the recommended dose (20 mg) approved in most districts. Hazard ratio (HR) with 95% confidence intervals (95% CIs) was pooled using a random-effect model. Subgroup analyses were conducted according to different dose regimens. Sensitivity analyses were conducted by sequential elimination of each study from the pool. Since potential effect modifiers (patient demographics, differences of each study, and others) may lead to bias in primacy outcomes, we performed a meta-regression analysis to explore the influence of these factors on the primary efficacy and safety outcomes.Results: Totally, 12 studies involving 292,815 Asian patients with AF were included. All studies were detected as low to moderate risk bias. Low-dose rivaroxaban treatment in Asian AF patients was associated with a reduced risk of stroke/systemic embolism (HR: 0.76, 95% CI: 0.70–0.84, I2: 57.8%), major bleeding (HR: 0.72, 95% CI: 0.62–0.84, I2: 81.5%), and all-cause death (HR: 0.65, 95% CI: 0.58–0.73, I2: 81.7%) when compared with warfarin. Furthermore, consistent results were observed among different dose regimens (10/15/20 mg) in all the clinical outcomes (Pinteraction > 0.05 for each outcome). Meta-regression analysis failed to detect any potential confounding to impact the primacy outcomes.Conclusion: Insights from the present meta-analysis, we found that low-dose rivaroxaban, even at a dosage of 10 mg daily, was associated with a reduced risk of stroke/SE and bleeding than warfarin in Asian AF patients. However, owing to considerable heterogeneity among included studies, further prospective studies are required to confirm these findings.

背景：在亚洲，房颤（AF）患者中低剂量使用利伐沙班处方较为普遍。然而，利伐沙班在亚洲房颤患者中低剂量应用的益处与风险尚不明确。鉴于此，本研究旨在收集并总结所有可用的证据，以填补这一重要的知识空白。方法：在本项系统评价和荟萃分析中，我们系统地检索了MEDLINE、EMBASE和Cochrane图书馆数据库，直至2021年2月23日，以获取相关研究。纳入标准为符合以下条件的回顾性全国性或健康保险数据库研究或前瞻性登记研究：报告了低剂量利伐沙班（15/10 mg）与华法林在房颤患者中疗效（卒中/全身性栓塞）、安全性（大出血、颅内出血、胃肠道出血）或其他结果（心肌梗死、死亡）的比较。数据提取和研究质量评估由两位作者独立完成。低剂量利伐沙班（15/10 mg）的定义为所接受的剂量低于大多数地区批准的推荐剂量（20 mg）。采用随机效应模型对危度比（HR）及其95%置信区间（95% CI）进行汇总。根据不同的剂量方案进行亚组分析。通过逐个排除每个研究从汇总中，进行敏感性分析。由于潜在效应修饰因子（患者人口统计学、各研究间的差异等）可能导致主要结果存在偏倚，我们进行了元回归分析，以探讨这些因素对主要疗效和安全性结果的影响。结果：共纳入12项研究，涉及292,815名亚洲房颤患者。所有研究均被判定为低至中度风险偏倚。与华法林相比，在亚洲房颤患者中，低剂量利伐沙班治疗与卒中/全身性栓塞（HR：0.76，95% CI：0.70–0.84，I2：57.8%）、大出血（HR：0.72，95% CI：0.62–0.84，I2：81.5%）和全因死亡（HR：0.65，95% CI：0.58–0.73，I2：81.7%）的风险降低相关。此外，在所有临床结果中，不同剂量方案（10/15/20 mg）均观察到一致的结果（每个结果的P交互作用均大于0.05）。元回归分析未能检测到任何可能影响主要结果的混杂因素。结论：本研究荟萃分析的结果表明，低剂量利伐沙班，即使每日剂量为10 mg，与华法林相比，在亚洲房颤患者中与卒中/SE和出血的风险降低相关。然而，由于纳入研究的异质性较大，需要进一步的前瞻性研究来证实这些发现。