Switching to DOAC associated with higher risk of bleeding in frail patients with AF

Safety of switching from a VKA blood thinner to a NOAC blood thinner in frail older patients with atrial fibrillation

News - Aug. 28, 2023

Presented at the ESC Congress 2023 by: Linda Joosten, MD - Utrecht, The Netherlands

Introduction and methods

The frailty syndrome is not just defined by high age, but also by the combination of having multiple diseases, taking a lot of medications, a high dependency on others and a reduced capacity to resist stressors. AF is very common among patients with the frailty syndrome, about 1 in 4 to 5 frail individuals have AF. To reduce the risk of stroke, these patients need to be treated with blood thinners, either VKA or DOAC.

Previous studies in non-frail patients have shown that DOACs have a more beneficial safety profile compared with VKA. However, there is no definitive evidence in frail patients. The FRAIL-AF was a pragmatic, investigator initiated, randomized, open-label trial that investigated the risk of bleeding in frail older patients (mean age 83 years, 38.8% women) who either switched from VKA to DOAC (n=662) or continued to use VKA (n=661). The choice of which specific DOAC was left to the discretion of the treating physician. The primary outcome was bleeding during 1 year of follow-up. Secondary outcomes were thromboembolic events (ischemic stroke, transient ischemic attack, and/or peripheral arterial thromboembolism).

Main results

- Patients who switched from a VKA to a DOAC had a 69% higher risk of major or clinically relevant non-major bleeding compared with patients who remained on a VKA (HR 1.69, 95%CI 1.23-2.32, P=0.00112).

- There was no significant difference in thromboembolic events (HR 1.26, 95%CI 0.60-2.61) and all-cause mortality (HR 0.96, 95%CI 0.64-1.45) between groups.


The FRAIL-AF trial showed that frail older patients with AF who switched from VKA to a DOAC had a 69% higher risk of bleeding, compared with patients who continued using VKA. There was no difference between DOACs and VKA in stroke reduction in this patient population. “Switching from a VKA to a DOAC should not be considered without a clear indication in frail older patients with AF ”, said Linda Joosten.

  • Our reporting is based on the information provided at the ESC Congress 2023 -

The results of this study were simultaneously published in Circulation.

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