Longer DOAC treatment reduces risk of recurrent VTE with no increased bleeding risk
Rivaroxaban treatment for six weeks versus three months in patients with symptomatic isolated distal deep vein thrombosis: randomised controlled trial
Introduction and methods
In case of isolated distal deep vein thrombosis (DVT), international guidelines recommend anticoagulation only for patients presenting with severe symptoms or those at increased risk of thrombus extension and surveillance ultrasonography for the remaining patients [1,2]. However, recent large observational studies have reported similar treatment strategies for the acute phase management in both patients with proximal and isolated distal DVT, although the treatment duration was shorter in the latter group [3,4]. Consequently, although most patients with isolated distal DVT are treated, the optimal treatment duration is still up for debate.
Aim of the study
The authors compared the efficacy and safety of two durations of rivaroxaban treatment in patients with symptomatic isolated distal DVT.
The RIDTS (Rivaroxaban for the treatment of symptomatic Isolated Distal deep vein ThrombosiS) study was a double blind, placebo controlled RCT conducted at 28 outpatient thrombosis clinics in Italy. In this study, 402 patients with an objective diagnosis of symptomatic isolated distal DVT of the legs first received a standard dose of rivaroxaban for 6 weeks (15 mg twice daily for 3 weeks, followed by rivaroxaban 20 mg once daily for 3 weeks). Thereafter, they were randomized to rivaroxaban 20 mg once daily or placebo for an additional 6 weeks. Exclusion criteria included active cancer, concomitant proximal DVT, or symptomatic pulmonary embolism. At baseline, 6 weeks, 3 months, and 24 months, all patients underwent compression ultrasonography.
The primary efficacy endpoint was the occurrence of recurrent venous thromboembolism (VTE) after randomization, defined as the composite outcome of progression of isolated distal DVT, recurrent isolated distal DVT, proximal DVT, symptomatic pulmonary embolism, or fatal pulmonary embolism. The primary safety endpoint was the incidence of major bleeding—defined according to the International Society of Thrombosis and Haemostasis criteria—after randomization until 2 days from the last dose of rivaroxaban or placebo.
- During follow-up, the primary efficacy endpoint was observed in 23 patients (12%) in the rivaroxaban group and 39 (19%) in the placebo group (relative risk (RR): 0.59; 95%CI: 0.36–0.95; P=0.03; number needed to treat: 13; 95%CI: 7–126), with an incidence rate of 6.6 per 100 patient-years (95%CI: 4.4–10.0) and 12.2 per 100 patient-years (95%CI: 4.9–30.8), respectively.
- Recurrent isolated distal DVT occurred in 16 patients (8%) in the rivaroxaban arm and 31 (15%) in the placebo arm (RR: 0.52; 95%CI: 0.29–0.92; P=0.02). The incidence of the other components of the primary efficacy endpoint, including proximal DVT or pulmonary embolism, did not differ between the rivaroxaban and placebo groups.
- As several baseline characteristics were unbalanced between the two groups, such as the prevalences of hypertension and previous surgical procedures, prespecified stratified risk analyses were performed but did not show any confounding effects.
- After randomization, no major bleeding events occurred. Two patients (1 in each study arm) experienced clinically relevant non-major bleeding events.
In patients with objectively diagnosed isolated distal DVT who had an uneventful 6-week treatment course of rivaroxaban, administration of rivaroxaban for an additional 6 weeks reduced the risk of recurrent VTE during 2-year follow-up compared with placebo. This was mainly due to a reduction in the occurrence of recurrent isolated distal DVT. The extended rivaroxaban treatment was not associated with an increased bleeding risk.
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