Low-dose DOACs linked to increased risk of bleeding in Afib patients

Reference: August 2024 | Issue 8 | Vol 10 | Page 58

Patients with atrial fibrillation (Afib) who took low doses of direct oral anticoagulants (DOACs) experienced more bleeding episodes during the first three months of treatment compared with similar patients who took standard doses of the same drugs, according to Italian research published recently in Blood Advances. Findings also show that about one-in-five of those who took low-dose DOACs had high blood levels of the medications compared to those on standard regimes.

Afib is the most common cardiac arrhythmia in Ireland, and although the condition can affect people at any age, it is more common in older patients. In the over-50 population, 400,000 have Afib, and one-in-four are at risk of developing it. At least 11 per cent of those over 80 in Ireland have the disorder, which is not in itself life-threatening, but contributes to a significantly elevated risk of negative outcomes including thrombosis and stroke.

Observational studies have shown that patients with Afib who are treated with DOACs have fewer strokes and blood clots than those treated with warfarin. Unlike warfarin, most patients treated with DOACs do not undergo regular tests to measure blood levels of the medication. However, recent studies have suggested that blood levels of DOACs can vary considerably between patients and that levels that are too low or too high may increase patients’ risk for blood clots and bleeding episodes. To reduce the risk of bleeding and other adverse effects associated with DOACs, clinicians may prescribe lower doses to patients deemed high risk, which the research suggests may be futile.

“We found that 58 per cent of bleeding complications occurred in patients who were treated with low doses of DOACs,” said study coordinator Dr Gualtiero Palareti, Arianna Anticoagulation Foundation, Bologna, Italy, who also noted that people with Afib often need these medications as a lifelong treatment. “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.”

Dr Palareti and his colleagues designed the ‘measure and see’ (MAS) study to examine whether a relationship existed between blood levels of DOACs, measured soon after initiating the drugs to treat Afib, and the occurrence of blood clots and bleeding episodes. The research had a sample population of 1,657 Afib patients with a median age of 80 years (54 per cent male).

The choice of DOAC prescribed was left up to the treating physician. Venous blood was collected from participants 15-to-30 days following DOAC commencement, and immediately before patients were due to take their next pill, when blood levels of the drug were expected to be at their lowest.

All blood samples were analysed in the same laboratory. Patients were then followed for one year to record the occurrence of clinically relevant adverse events. Researchers recorded all bleeding events, blood clots, strokes, heart attacks, deaths due to a stroke or heart disease, and other adverse events during the 12-month follow-up period. Primary endpoints for the study were major bleeding and bleeding requiring medical intervention, hospitalisation, or evaluation.

Results showed that 50 patients (3.1 per cent) experienced bleeding events, of which 29 (58 per cent) occurred in patients treated with low doses of a DOAC. About one-third of all recorded bleeding events occurred in patients with the highest blood levels of their medication during the first three months of treatment.

“Our findings indicate that treatment with low doses of a DOAC does not necessarily prevent the occurrence of high blood levels of the drug,” said Dr Palareti. “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.”

After the first three months, the risk of bleeding events was not associated with either low-dose treatment or blood levels of the medication, which “suggests that the risk of bleeding events during anticoagulant treatment is multicausal”, according to Dr Palareti.

He added that the findings suggest potential benefits of measuring medication levels in a patient’s blood shortly after initiating DOAC treatment and tailoring the medication dose accordingly to avoid excessively low or high blood levels and reduce bleeding and clotting complications, especially in patients who are prescribed low-dose treatment. He and his colleagues are planning to conduct a pilot clinical trial to test this approach.