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Patients with venous thromboembolism (VTE) who require extended treatment with direct oral anticoagulants (DOACs) do not necessarily gain an advantage from standard doses compared with reduced doses, researchers have reported.
The study, published in The Lancet on 1 March 2025, analysed data from 2,768 patients across 47 hospitals in France who were taking apixaban or rivaroxaban between November 2017 to July 2022.
It assessed what the authors called “non-inferiority” of a reduced dose, compared with a full dose, in people at high risk of recurrent thromboembolic events, with a five-year follow-up period.
The study was not able to demonstrate non-inferiority of the reduced dose and recorded “reliably low rates of recurrent VTE in both groups”.
Recurrent VTE occurred in 19 out of 1,383 patients in the reduced-dose group (five-year cumulative incidence 2.2% (95% confidence interval (CI) 1.1%–3.3%) versus 15 of 1,385 patients in the full-dose group (five-year cumulative incidence 1.8%, 0.8%–2.7%; adjusted HR 1.32, 95% CI 0.67%–2.60%).
However, the study did find a reduction in the risk of major and clinically relevant non-major bleeding in the reduced-dose group.
Major or clinically relevant bleeding occurred in 96 patients in the reduced-dose group (five-year cumulative incidence 9.9%, 95% CI 7.7%–12.1%) and 154 patients in the full-dose group (five-year cumulative incidence 15.2%, 12.8%–17.6%; adjusted HR 0.61, 95% CI 0.48%–0.79%).
The authors said that instances of major or clinically relevant bleeding “did not appear to be offset by an increased risk of death or arterial thromboembolic events”.
In addition, further research to identify subgroups for which a full dose remains the best option would be valuable, the authors added.
Commenting on the study, Frances Akor, consultant pharmacist in anticoagulation at Imperial College Healthcare NHS Trust, said: “Routine practice for patients assessed as requiring extended anticoagulation to prevent VTE recurrence has been to reduce the dose of the DOAC after completion of the treatment phase with standard treatment dose DOAC, which is usually after six months.
“However, there is recognition that a more tailored approach is required. The manufacturers of rivaroxaban advise in patients at high risk of VTE recurrence that the standard treatment dose of rivaroxaban should be considered. Many clinicians also adopt this approach for apixaban, although there is not wide-spread consensus due to a lack of evidence to inform management of this clinical scenario.
“[The results] speak to the balancing act that clinicians are faced with every day in determining an appropriate dose of anticoagulation for this patient group: a dose that is high enough to adequately prevent thrombotic events but with an acceptable bleed profile,” she added.
An individualised approach that “considers and balances patients’ specific thrombotic and bleed risks and involves the patient/carer in the decision-making process is required to support dose selection”, Akor said.
“Further data that support the refinement of dose selection for extended VTE treatment, particularly in specific high-risk patient groups, are welcome.”
