Recurrent Venous Thromboembolism After Isolated Distal DVT: Insights from the RIDTS Trial

Highlight

The post-hoc analysis of the RIDTS trial reveals: (1) a notable incidence of recurrent venous thromboembolism (VTE) after treatment for isolated distal deep vein thrombosis (IDDVT); (2) shorter anticoagulation duration, diabetes, and unprovoked IDDVT significantly increase recurrence risk; (3) extending rivaroxaban therapy from 6 to 12 weeks reduces early recurrence; (4) recurrent events include both distal and proximal thromboses, with a majority symptomatic.

Study Background

Isolated distal deep vein thrombosis (IDDVT), involving thrombus confined to calf veins, represents a clinical entity with variable risk for recurrence and embolic complications. While proximal deep vein thrombosis (DVT) and pulmonary embolism (PE) management guidelines are well-established, the optimal treatment duration and risk stratification for IDDVT remain uncertain. Contemporary evidence on long-term recurrence after anticoagulation for IDDVT is sparse, especially regarding direct oral anticoagulants (DOACs) like rivaroxaban. Understanding recurrence patterns and predictors after anticoagulation cessation is vital to optimize secondary prevention and individualize treatment.

Study Design

The RIDTS (Rivaroxaban for the treatment of symptomatic Isolated Distal deep vein ThrombosiS) trial was a randomized, double-blind, multicenter study evaluating 6 versus 12 weeks of rivaroxaban treatment in patients with IDDVT without active cancer. This post-hoc analysis included 398 participants, aiming to assess the incidence of recurrent VTE and identify predictors of recurrence following treatment cessation. The primary endpoints included recurrence of any symptomatic or asymptomatic VTE, proximal DVT, or symptomatic PE during both short- and long-term follow-up periods.

Key Findings

Out of 398 patients, 61 (15.3%) experienced recurrent VTE with a median time to recurrence of 6.2 months after stopping anticoagulation. Among these recurrences, 77% were isolated distal DVT, whereas 23% were proximal events (14.8% proximal DVT, 8.2% PE). About 64% of recurrences were symptomatic, and no deaths were attributed to pulmonary embolism during follow-up.

The incidence rates per 100 person-years for any recurrence were 15.8 at 6 months and 10.0 at 24 months after anticoagulation cessation. Notably, patients with unprovoked IDDVT had a higher recurrence rate compared with those with provoked IDDVT; the 24-month recurrence incidence was 15.7 vs 4.5 per 100 person-years respectively.

Dosing duration influenced recurrence significantly: patients receiving 6 weeks of rivaroxaban had substantially higher early recurrence (24.4 per 100 person-years at 6 months) compared with those treated for 12 weeks (7.5 per 100 person-years at 6 months). Multivariable Cox proportional hazards modeling identified short anticoagulation duration (HR 1.8, 95% CI 1.1-3.0), diabetes mellitus (HR 2.5, 95% CI 1.1-5.3), and unprovoked IDDVT (HR 3.2, 95% CI 1.7-5.7) as independent predictors of recurrent VTE.

Clinical Implications

The findings underscore that IDDVT is not uniformly benign and that recurrence rates, especially early post-treatment, can be substantial in selected subsets. Longer anticoagulation duration mitigates recurrence risk, supporting extended therapy beyond 6 weeks in higher-risk patients. Furthermore, presence of diabetes and unprovoked nature of IDDVT help identify patients who might benefit from intensified surveillance or longer anticoagulation.

Expert Commentary

Current guidelines for IDDVT recommend a variable approach, often favoring shorter anticoagulation due to perceived lower risk. However, this analysis challenges the notion by demonstrating clinically relevant recurrence risks. The predominance of recurrent events in the distal veins suggests that these thrombi retain embolic potential, warranting careful follow-up. The study also confirms the value of risk-adapted strategies, considering patient comorbidities and provoking factors.

Limitations include the post-hoc nature of the analysis and the exclusion of cancer patients, which may limit generalizability. Additionally, the relatively small sample size and event number constrain subgroup analyses. Larger prospective studies are needed to refine risk models and guide duration of therapy.

Conclusion

In patients with isolated distal DVT treated with rivaroxaban, recurrence after anticoagulation cessation is not infrequent, particularly in those with unprovoked events, diabetes, or shorter treatment durations. Extending anticoagulation to 12 weeks reduces early recurrence risk. These insights enhance risk stratification, guiding individualized treatment duration and monitoring strategies to improve outcomes in IDDVT management.

Funding and ClinicalTrials.gov

The RIDTS trial was supported by institutional grants and conducted under appropriate ethical oversight. The specific clinical trial registration and funding details can be accessed through the original publication.

References

Potere N, Bertù L, Bucherini E, et al. Incidence and predictors of recurrent venous thromboembolism after isolated distal deep vein thrombosis: a post-hoc analysis of the RIDTS trial. Haematologica. 2026 Jul 2. PMID: 42389836. Available at: https://pubmed.ncbi.nlm.nih.gov/42389836/.

Kearon C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest. 2016 Feb;149(2):315-352.

Robert-Ebadi H, Le Gal G, Carrier M. Isolated distal deep vein thrombosis: Diagnosis and treatment. J Thromb Haemost. 2021;19(2):299-308.