Ahmed Mushood, Zulfiqar Eeshal, Ashraf Hadiah, Hashmi Tallal Mushtaq, Ahmed Raheel, Rana Jamal S, Greene Stephen J, Mentz Robert J, Fudim Marat, Fonarow Gregg C
Rawalpindi Medical University, Rawalpindi, Pakistan.
Dow University of Health Sciences, Karachi, Pakistan.
Res Pract Thromb Haemost. 2025 Aug 5;9(5):102996. doi: 10.1016/j.rpth.2025.102996. eCollection 2025 Jul.
Venous thromboembolism (VTE) is a major cause of cardiovascular morbidity and mortality globally. Although direct oral anticoagulants (DOACs) have improved extended VTE treatment, the optimal dose for balancing efficacy and safety remains unclear.
This systematic review and meta-analysis aimed to evaluate the efficacy and safety of reduced-dose DOACs vs full-dose regimens during extended anticoagulation for VTE.
A literature search of PubMed, Embase, and Cochrane Library was performed up to April 2025 to identify randomized controlled trials (RCTs) comparing reduced-dose vs full-dose DOACs for extended VTE treatment in patients with or without cancer. Risk ratios (RR) and 95% CIs were estimated using a random-effects model. Primary outcomes were recurrent VTE and major or clinically relevant nonmajor bleeding. The secondary outcomes included major bleeding, clinically relevant nonmajor bleeding, all-cause mortality, and VTE-related mortality.
Five RCTs involving 8781 patients were included in the meta-analysis. The mean ± SD age of patients was 61.3 ± 13.4 years, and median follow-up duration was 12 months. Reduced-dose DOACs were comparable with full-dose regimens in preventing recurrent VTE (RR, 0.94; 95% CI, 0.68-1.29) and all-cause death (RR, 0.86; 95% CI, 0.63-1.17). However, reduced-dose DOACs significantly lowered the risk of major or clinically relevant nonmajor bleeding (RR, 0.71; 95% CI, 0.61-0.82), major bleeding (RR, 0.62; 95% CI, 0.42-0.92), and clinically relevant nonmajor bleeding (RR, 0.75; 95% CI, 0.63-0.88) compared with full-dose regimens. No significant subgroup differences were observed between cancer-associated and general VTE populations.
Reduced-dose DOACs are as effective as full-dose regimens in preventing recurrent VTE and are associated with significantly lower bleeding risks. However, more RCTs with extended follow-up and focused inclusion of cancer patients are warranted to validate these findings.
静脉血栓栓塞症（VTE）是全球心血管疾病发病和死亡的主要原因。尽管直接口服抗凝剂（DOACs）改善了VTE的长期治疗，但平衡疗效和安全性的最佳剂量仍不明确。
本系统评价和荟萃分析旨在评估在VTE长期抗凝治疗中，低剂量DOACs与全剂量方案的疗效和安全性。
截至2025年4月，对PubMed、Embase和Cochrane图书馆进行文献检索，以识别比较低剂量与全剂量DOACs用于有或无癌症患者VTE长期治疗的随机对照试验（RCTs）。使用随机效应模型估计风险比（RR）和95%置信区间（CIs）。主要结局为复发性VTE和大出血或临床相关非大出血。次要结局包括大出血、临床相关非大出血、全因死亡率和VTE相关死亡率。
荟萃分析纳入了5项涉及8781例患者的RCTs。患者的平均年龄±标准差为61.3±13.4岁，中位随访时间为12个月。低剂量DOACs在预防复发性VTE（RR，0.94；9⫽%CI，0.68-1.29）和全因死亡（RR，0.86；95%CI，0.63-1.17）方面与全剂量方案相当。然而，与全剂量方案相比，低剂量DOACs显著降低了大出血或临床相关非大出血（RR，0.71；95%CI，0.61-0.82）、大出血（RR，0.62；95%CI，0.42-0.92）和临床相关非大出血（RR，0.75；95%CI，0.63-0.88）的风险。在癌症相关VTE人群和一般VTE人群之间未观察到显著的亚组差异。
低剂量DOACs在预防复发性VTE方面与全剂量方案同样有效，且出血风险显著降低。然而，需要更多随访时间更长且重点纳入癌症患者的RCTs来验证这些发现。
