10 June 2024

A new study by Italian researchers suggests that low-dose direct oral anticoagulants (DOACs) are associated with an increase in early bleeding episodes among patients with atrial fibrillation, compared with standard-dose DOAC.

A significant minority of patients receiving low-dose DOACs also retained high blood levels of the medication, according to a report in Blood Advances.

The researchers are planning a trial of new approaches to reduce bleeding risk from DOACs.

The findings come from the ‘Measure and See’ (MAS) study, which involved 1,657 patients treated for atrial fibrillation with DOACs, with a median age of 80, at 27 centres in Italy. The choice of treatment and dose was left to the doctor treating the patient.

In the study, 50 patients experienced bleeding events – with 29 (58%) of these having been treated with low-dose DOACs.

In the first three months after starting DOACs, patients with the highest steady-state levels of the DOACs in the blood had a significantly higher risk of bleeds, compared to those with lower levels of the drugs in the blood. However, after three months, there was no difference.

19% of patients who received low-dose DOAC had the highest levels of drug in the blood.

Study leader Dr Gualtiero Palareti said: “Not only did the use of low doses not reduce bleeding risk, it also did not prevent patients from developing high blood levels of the medication.   

“Our findings indicate that treatment with low doses of a direct oral anticoagulant does not necessarily prevent the occurrence of high blood levels of the drug. This predisposes patients to a higher risk of bleeding during the first three months of treatment – a period when the risk of bleeding due to oral anticoagulants is already elevated.”

The researchers, from the Arianna Anticoagulation Foundation in Bologna, Italy, are planning a pilot trial to test whether monitoring drugs levels in the blood of patients can help tailor doses and reduce the risk of complications.


Palareti G, Testa S, Legnani C, Dellanoce C, Cini M, Paoletti O, Ciampa A, Antonucci E, Poli D, Morandini R, Tala M, Chiarugi P, Santoro RC, Iannone AM, De Candia E, Pignatelli P, Faioni EM, Chistolini A, Esteban MDP, Marietta M, Tripodi A, Tosetto A. (2024) “More early bleeds associated with high baseline direct anticoagulant levels in atrial fibrillation: The MAS Study.” Blood Advances, 6 June 2024, doi: 10.1182/bloodadvances.2024013126.

Link: https://ashpublications.org/bloodadvances/article/doi/10.1182/bloodadvances.2024013126/516363/MORE-EARLY-BLEEDS-ASSOCIATED-WITH-HIGH-BASELINE


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