Rivaroxaban treatment for six weeks versus three months in patients with symptomatic isolated distal deep vein thrombosis: randomised controlled trial

Abstract

Objective To compare two different treatment durations of rivaroxaban in patients with symptomatic isolated distal deep vein thrombosis (DVT). Design Randomised, double blind, placebo controlled clinical trial. Setting 28 outpatient clinics specialising in venous thromboembolism. Participants 402 adults (≥18 years) with symptomatic isolated distal DVT. Interventions After receiving standard dose rivaroxaban for six weeks, participants were randomly assigned to receive rivaroxaban 20 mg or placebo once daily for an additional six weeks. Follow-up was for 24 months from study inclusion. Main outcomes measures The primary efficacy outcome was recurrent venous thromboembolism during follow-up after randomisation, defined as the composite of progression of isolated distal DVT, recurrent isolated distal DVT, proximal DVT, symptomatic pulmonary embolism, or fatal pulmonary embolism. The primary safety outcome was major bleeding after randomisation until two days from the last dose of rivaroxaban or placebo. An independent committee adjudicated the outcomes. Results 200 adults were randomised to receive additional rivaroxaban treatment and 202 to receive placebo. Isolated distal DVT was unprovoked in 81 (40%) and 86 (43%) patients, respectively. The primary efficacy outcome occurred in 23 (11%) patients in the rivaroxaban arm and 39 (19%) in the placebo arm (relative risk 0.59, 95% confidence interval 0.36 to 0.95; P=0.03, number needed to treat 13, 95% confidence interval 7 to 126). Recurrent isolated distal DVT occurred in 16 (8%) patients in the rivaroxaban arm and 31 (15%) in the placebo arm (P=0.02). Proximal DVT or pulmonary embolism occurred in seven (3%) patients in the rivaroxaban arm and eight (4%) in the placebo arm (P=0.80). No major bleeding events occurred. Conclusions Rivaroxaban administered for six additional weeks in patients with isolated distal DVT who had an uneventful six week treatment course reduces the risk of recurrent venous thromboembolism, mainly recurrent isolated distal DVT, over a two year follow-up without increasing the risk of haemorrhage. Trial registration EudraCT 2016-000958-36; ClinicalTrials.gov NCT02722447 .

Edoxaban for 12 Months Versus 3 Months in Patients With Cancer With Isolated Distal Deep Vein Thrombosis (ONCO DVT Study): An Open-Label, Multicenter, Randomized Clinical Trial

“…11 Another recent randomized clinical trial, the RIDTS study (Rivaroxaban Treatment for Six Weeks Versus Three Months), showed that rivaroxaban administered for 6 additional weeks in patients with isolated distal DVT who had an uneventful 6-week treatment course reduced the risk of recurrent VTE. 13 However, these studies excluded patients with active cancer, who were considered at high risk for thrombotic events. The American College of Chest Physicians 2021 guidelines weakly recommend that patients with isolated distal DVT with active cancer should receive anticoagulation therapy, and the anticoagulation strategy should be the same as that for patients with proximal DVT, which means that an extended duration of anticoagulation therapy might be recommended.…”

“…6 A previous study reported that approximately 4.6% of patients with cancer had distal DVT. 7 Despite the relatively high frequency of isolated distal DVT in patients with cancer, [8][9][10] previous clinical trials evaluating isolated distal DVT excluded patients with cancer, [11][12][13] which resulted in a huge uncertainty of the optimal management strategies including the duration of the anticoagulation therapy and subtypes of distal DVT. 14 However, a previous observational study showed that patients with cancer with isolated distal DVT were usually treated with a limited duration period of anticoagulation therapy and were at a relatively high risk of recurrent VTE after discontinuation of the anticoagulation therapy, 15 which suggested that those patients might benefit from prolonged anticoagulation therapy.…”

A two-sample Mendelian randomization study of circulating lipids and deep venous thrombosis

“…Deep venous thrombosis (DVT) is a common venous thromboembolism that usually affects the lower extremities. The annual incidence rate is close to 1.6 per 1000 people 1 . Thrombosis usually begins in the deep vein of the leg and spreads proximally.…”

Anticoagulation in Patients with Isolated Distal Deep Vein Thrombosis: Bringing the Puzzle Together

“…14 The RIDTS trial recently addressed the important question of whether anticoagulation for 3 months is superior to 6 weeks in symptomatic outpatients with acute IDDVT and no active cancer. 5 After completing uneventful 6 weeks of standard-dose rivaroxaban (15 mg twice daily), 402 subjects were randomized to receive rivaroxaban 20 mg or placebo once daily for 6 additional weeks, and followed for 2 years. 5 Recurrent VTE occurred in 11% and 19% of subjects in the rivaroxaban and placebo groups, respectively (relative risk, 0.59; 95% confidence interval, 0.36-0.95; P=0.03).…”

“…IDDVT has long been understudied until recent times. This Editorial Focus outlines latest relevant research findings with particular attention to two recent randomized controlled studies, namely the RIDTS 5 and ONCO DVT 6 trials, and discusses how these may advance personalized management of patients with IDDVT.…”