Alam Umama, Ali Muhammad Abdullah, Ansab Muhammad, Rath Shree, Khattak Fazia, Bacha Zaryab, Siddiqui Hafiza Tooba, Sajjad Fatima, Afridi Abdullah, Afridi Zarar Ahmad Khan, Ahmad Osama, Moiz Abdul, Aslam Bilal, Ahmed Raheel
Khyber Medical College, Peshawar, Pakistan.
Services Institute of Medical Sciences, Lahore, Pakistan.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Jul 22. doi: 10.1007/s00210-025-04388-1.
Venous thromboembolism (VTE), comprising deep vein thrombosis (DVT) and pulmonary embolism (PE), is a leading cause of cardiovascular-related death. Anticoagulation therapy is effective in preventing recurrence but poses a risk of bleeding. Reduced-dose factor Xa inhibitors (FXI) have been proposed as a long-term strategy to balance efficacy and safety. This systematic review and meta-analysis aims to assess the safety and efficacy of reduced-dose FXIs compared to full-dose FXIs for long-term treatment of VTE. Relevant studies were identified through a comprehensive search in PubMed, Embase, and Cochrane. Studies were included if they were randomized controlled trials (RCTs) comparing reduced-dose and full-dose FXIs for VTE treatment. Statistical analysis was conducted using R software, applying DerSimonian and Laird's random effects model to compute pooled estimates with 95% confidence intervals (CIs). The analysis included five studies with a total of 8421 patients. Reduced-dose DOACs significantly lowered the risk of major and non-major clinically relevant bleeding (CRB) (RR = 0.71; 95%CI = 0.61, 0.82) and clinically relevant non-major bleeding (CRNMB) (RR = 0.75; 95%CI = 0.63, 0.88; P = 0.0006). There was no significant difference in the risk of major bleeding or all-cause death. The risk of thromboembolism recurrence, pulmonary embolism, upper limb DVT, and lower limb DVT was comparable between both groups. Reduced-dose FXIs offer a safer alternative with significantly lower risks of CRB and CRNMB while maintaining similar efficacy to full-dose regimens for preventing thromboembolism recurrence. These findings suggest that reduced-dose FXIs could be beneficial for long-term anticoagulation therapy, particularly in patients at higher risk of bleeding.
静脉血栓栓塞症（VTE），包括深静脉血栓形成（DVT）和肺栓塞（PE），是心血管相关死亡的主要原因。抗凝治疗在预防复发方面有效，但存在出血风险。降低剂量的Xa因子抑制剂（FXI）已被提议作为平衡疗效和安全性的长期策略。本系统评价和荟萃分析旨在评估与全剂量FXI相比，降低剂量的FXI用于VTE长期治疗的安全性和疗效。通过在PubMed、Embase和Cochrane中进行全面检索来识别相关研究。纳入的研究需为比较降低剂量和全剂量FXI治疗VTE的随机对照试验（RCT）。使用R软件进行统计分析，应用DerSimonian和Laird随机效应模型计算合并估计值及95%置信区间（CI）。该分析纳入了5项研究，共8421例患者。降低剂量的直接口服抗凝剂（DOAC）显著降低了主要和非主要临床相关出血（CRB）风险（RR = 0.71；95%CI = 0.61，0.82）以及临床相关非主要出血（CRNMB）风险（RR = 0.75；95%CI = 0.63，0.88；P = 0.0006）。主要出血或全因死亡风险无显著差异。两组之间血栓栓塞复发、肺栓塞、上肢DVT和下肢DVT的风险相当。降低剂量的FXI提供了一种更安全的选择，CRB和CRNMB风险显著降低，同时在预防血栓栓塞复发方面保持与全剂量方案相似的疗效。这些发现表明，降低剂量的FXI可能有利于长期抗凝治疗，尤其是在出血风险较高的患者中。
