Angiology and Blood Coagulation Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
Cardiovascular Medicine Unit - AUSL-IRCCS, Reggio Emilia, Italy.
Am J Hematol. 2024 May;99(5):854-861. doi: 10.1002/ajh.27255. Epub 2024 Feb 20.
Current guidelines suggest a 3-month anticoagulant treatment course for isolated distal deep vein thrombosis (IDDVT), but shorter durations of treatment are frequently prescribed in clinical practice. We investigated whether a 6-week treatment with low-molecular-weight heparin (LMWH) at intermediate dosage can be an effective and safe alternative to vitamin K antagonists (VKA) in patients with IDDVT (non-inferiority trial). In a multicenter, open-label, randomized trial, 260 outpatients with symptomatic IDDVT were randomly assigned to receive either LMWH followed by VKA for 12 weeks or LMWH 1 mg/kg subcutaneously twice a day for 2 weeks followed by 1 mg/kg subcutaneously once a day for 4 weeks. The follow-up was 6 months and the primary endpoint was the composite measure of recurrent venous thromboembolism (VTE) defined as: recurrence or extension of IDDVT, proximal DVT, and pulmonary embolism (PE). The study was stopped prematurely due to slow recruiting rates. The primary efficacy outcome occurred in 14 patients receiving LMWH (10.8%) and in five patients receiving VKA (3.8%); risk difference was 0.069 (95% CI: 0.006-0.132), hazard ratio 2.8 (95% CI: 1.04-7.55). There was one PE in the VKA group and one proximal DVT in the LMWH group. IDDVT recurrence was 10.0% in the LMWH group versus 3.1% in the VKA group (p = .024). Two patients had clinically relevant bleedings (1.6%) in the LMWH group versus one (0.8%) in VKA group (p = .56). In conclusion, VKA for 12 weeks seems superior to LMWH for 6 weeks in reducing the risk of VTE recurrences in our cohort of outpatients with IDDVT.
目前的指南建议对孤立的远端深静脉血栓形成（IDDVT）进行 3 个月的抗凝治疗，但在临床实践中经常开具更短疗程的治疗。我们研究了中剂量低分子量肝素（LMWH）治疗 6 周是否可以替代维生素 K 拮抗剂（VKA）作为 IDDVT（非劣效性试验）患者的有效和安全替代方法。在一项多中心、开放标签、随机试验中，260 名有症状的 IDDVT 门诊患者被随机分配接受 LMWH 治疗 12 周后再接受 VKA 治疗或 LMWH 1mg/kg 皮下注射，每日两次，持续 2 周，然后每日一次，持续 4 周。随访时间为 6 个月，主要终点是复发性静脉血栓栓塞症（VTE）的综合测量，定义为：IDDVT、近端 DVT 和肺栓塞（PE）的复发或延伸。由于招募速度缓慢，该研究提前终止。接受 LMWH 治疗的 14 名患者（10.8%）和接受 VKA 治疗的 5 名患者（3.8%）发生主要疗效结局；风险差异为 0.069（95%CI：0.006-0.132），风险比为 2.8（95%CI：1.04-7.55）。VKA 组发生 1 例 PE，LMWH 组发生 1 例近端 DVT。LMWH 组 IDDVT 复发率为 10.0%，VKA 组为 3.1%（p=0.024）。LMWH 组有 2 例患者（1.6%）发生临床相关出血，VKA 组有 1 例（0.8%）（p=0.56）。总之，在我们的 IDDVT 门诊患者队列中，VKA 治疗 12 周似乎比 LMWH 治疗 6 周更能降低 VTE 复发的风险。
