A new U.S. study published in the BMJ reports that continuing anticoagulant therapy beyond the initial 90 days after a first venous thromboembolism (VTE) substantially reduces the risk of recurrent clots. Using large real-world datasets drawn from routine clinical practice across the country, researchers found that patients with unprovoked VTE achieved markedly better long-term outcomes when oral anticoagulants (OACs) were maintained rather than stopped at the three-month mark.
Anticoagulants work by interrupting the body’s natural clotting process, specifically by inhibiting key clotting factors that drive the biochemical cascade responsible for clot formation. These medications are standard therapy after a first VTE, but the optimal duration of treatment has long been debated.
The investigation analyzed more than 30,000 matched patient pairs from the Optum Clinformatics Data Mart (2009–2025) and Medicare claims databases (2009–2022). Participants, with a mean age of 73.9 years, had been treated with either warfarin or direct oral anticoagulants following a first unprovoked clot. When compared with those who discontinued treatment after completing at least 90 days of therapy, patients who continued anticoagulation experienced an 81% reduction in recurrent VTE, reflected by an adjusted hazard ratio of 0.19. This protective effect remained consistent across treatment durations ranging from three months to more than three years.
Extended therapy, however, was associated with a higher risk of major bleeding, with a hazard ratio of 1.75. Even so, the overall clinical benefits outweighed the risks. Mortality was 26% lower among those who stayed on anticoagulants, and the combined endpoint of recurrent clot plus major bleeding favored continuation of therapy. The advantages were observed regardless of the type of anticoagulant used or the duration of prior treatment.
Supporting these findings, earlier work by Fahrni and colleagues showed that patients with residual thrombosis who extended therapy for an additional nine months had a recurrence rate of only 1.3%, compared with 27.2% in those who stopped treatment prematurely.
According to the authors, real-world evidence offers a more practical view of patient outcomes than traditional clinical trials, capturing the complexities of everyday clinical decision-making. While the increased bleeding risk underscores the importance of individualized care, the study reinforces current guideline recommendations that many patients with unprovoked VTE stand to benefit from long-term anticoagulation.
Overall, the findings strengthen the growing consensus that extending anticoagulant therapy beyond the initial treatment window significantly improves long-term outcomes, reducing both recurrence and death, provided that patients are closely monitored to manage bleeding risk.
References
- Lin KJ, Kim DH, Singer DE, Zhang Y, Cervone A, Kehoe AR, et al. Continued versus discontinued oral anticoagulant treatment for unprovoked venous thromboembolism: target trial emulation. 2025 Nov 12 [cited 2025 Nov 17]; Available from: https://www.bmj.com/content/391/bmj-2025-084380
- Zesh M. Anticoagulant Drugs: Understanding their Mechanism and Clinical Applications. Interventional Pediatrics & Research. 2023 June 30;6(3):1–3.
- Fahrni J, Husmann M, Gretener SB, Keo HH. Assessing the risk of recurrent venous thromboembolism–a practical approach. Vasc Health Risk Manag. 2015 Aug 17;11:451-9.