DOACs outperform VKAs for lower-limb thrombosis

Direct oral anticoagulants were linked to fewer recurrent clots and major bleeds, but more bothersome non-major bleeding.
*Prospective registry cohort study; Level 2 (OCEBM).

Citation

Prandoni P, Pesavento R, Bilora F, et al. Recurrent venous thromboembolism and bleeding during anticoagulation in patients with deep-vein thrombosis treated with vitamin K antagonists or direct oral anticoagulants: insights from the RIETE registry. European Journal of Internal Medicine. 2026. doi:10.1016/j.ejim.2026.107120

Background

Prior randomized trials found direct oral anticoagulants as effective as vitamin K antagonists for venous clots, with less major bleeding. This study tested whether those results hold in routine care, including patients often excluded from trials.

Patients

24,728 adults with confirmed symptomatic lower-limb deep-vein thrombosis, with or without lung clot symptoms. Exclusions included isolated lung clots, clot sites outside the lower limb, pregnancy, age under 18 years, and anticoagulant use before diagnosis.

Intervention

Therapeutic-dose direct oral anticoagulants: rivaroxaban, apixaban, edoxaban, or dabigatran.

Control

Therapeutic-dose vitamin K antagonists.

Outcome

Recurrent venous clot, major bleeding, and clinically relevant non-major bleeding.

Follow-up Period

During active full-dose anticoagulant treatment only; median treatment was 5.1 months with direct oral agents and 6.7 months with vitamin K antagonists.

Results

Outcome Direct oral anticoagulants Vitamin K antagonists Adjusted effect
Recurrent clot 1.81 per 100 patient-years 2.12 per 100 patient-years HR 0.71 (95% CI 0.58 to 0.87)
Major bleeding 1.50 per 100 patient-years 1.67 per 100 patient-years HR 0.78 (95% CI 0.63 to 0.97)
Clinically relevant non-major bleeding 4.86 per 100 patient-years 3.08 per 100 patient-years HR 1.35 (95% CI 1.17 to 1.55)

HR = hazard ratio. Approximate absolute effects from crude rates: about 323 patient-years treated to prevent one recurrent clot, 588 to prevent one major bleed, and 56 to cause one non-major bleed.

Results were adjusted observational analyses during treatment. Trial-eligible patients had clearer major bleeding benefit; trial-ineligible patients did not.

Limitations

Non-randomized treatment choice may leave residual bias. Warfarin control quality was unavailable. Trial eligibility was approximate, follow-up ended at treatment stopping, and isolated lung clots were excluded.

Funding

Unrestricted educational grant from ROVI; potential industry-support bias.

Clinical Application

Use direct oral anticoagulants first for most lower-limb thrombosis patients, but individualize in high-risk patients and warn about non-major bleeding.