Bleeding risk in frail patients with AF switching from vitamin K antagonist to nonvitamin K antagonist oral anticoagulant therapy

By Rebecca Jenkins

Frail older people with atrial fibrillation (AF) should not be switched from vitamin K antagonist (VKA) treatment to a non-VKA oral anticoagulant (NOAC) without a clear indication, a study suggests.

Landmark trials have shown NOAC treatment to be associated with a lower risk of major bleeding than VKA therapy with similar efficacy for stroke prevention, Dutch researchers wrote in Circulation. However, there was still a large population of older patients with AF being treated with VKAs, at least in part due to the lack of convincing trial evidence on the superiority of NOACs in this population.

In the FRAIL-AF trial, researchers randomised 1330 older patients with nonvalvular AF living with frailty to either switch from international normalised ratio (INR)-guided VKA treatment to a NOAC or continue with VKA treatment for 12 months.

Patients aged 75 years or older with a Groningen Frailty Indicator (GFI) score 3 or higher were eligible for the trial, with participants having a mean age of 83 years. Anyone with a glomerular filtration rate less than 30mL/min/1.73m² was excluded.

Researchers hypothesised that switching to NOAC therapy would lead to fewer major and/or clinically relevant nonmajor bleeding; however, the trial was stopped for futility after they observed 163 primary outcome bleeding events (101 in the NOAC-arm [15.3%] and 62 [9.4%] in the VKA-arm).

After completing follow up, researchers found switching therapies was associated with a 69% increase in major and/or clinically relevant nonmajor bleeding.

The higher bleeding risk was not offset by a reduction in thromboembolic events, the researchers added, although the risk of such events was low in both treatment arms.

Associate Professor John Amerena, Director of Cardiology Research at University Hospital Geelong in Victoria, said the findings were likely to make clinicians less likely to swap patients on well-controlled VKA therapy to a NOAC unless there was a specific reason to change, such as unstable INRs.

‘But bleeding on VKA [therapy] in a patient with stable INRs will probably not be an indication to swap, given this study, whereas it would have been in the past,’ he told Medicine Today.

Professor Amerena said that nevertheless the study did have limitations including participants being particularly stable on VKA therapy, which might have affected results in favour of that therapy.

Dr Hannah Stevens, Research Officer and Consultant Haematologist at the Baker Heart and Diabetes Institute in Melbourne, also welcomed the research, but added that one significant limitation was the lack of detailed information about the dosing of NOACs.

‘In Australia, it’s common practice to adjust the dose based on a range of factors,’ she said.

‘While the study suggests that full-dose NOACs may be associated with a higher risk of bleeding, it’s challenging to directly apply these findings to how we currently prescribe in Australia.’

Circulation 2023; doi.org/10.1161/CIRCULATIONAHA.123.066485.