Starting DOACs sooner after stroke may be best for AF patients

For secondary stroke prevention in patients with atrial fibrillation (AF), the optimal timing of initiating a direct oral anticoagulant (DOAC) remains elusive, although evidence from a phase II study suggests that earlier initiation is better than later times within the first 2 weeks after stroke onset.

In a cohort of 200 AF patients (median age 75 years, 50 percent female, 16.5 percent Hispanic) who had a mild-to-moderate ischaemic stroke and subsequently received a DOAC prescription, 10 primary outcome events—including seven ischaemic (stroke or systemic embolism) and three haemorrhagic (symptomatic intracranial haemorrhage or major systemic haemorrhage) strokes—had been documented by day 30 after the onset of the index stroke event. [JAMA Neurol 2025;82:470-476]

Specifically, one haemorrhagic event occurred among patients who initiated DOACs at day 3 or 4 after stroke onset (group 1), three ischaemic and one haemorrhagic events among those who initiated DOACs at day 6 (group 2), two ischaemic and one haemorrhagic events among those who initiated DOACs at day 10 (group 3), and two ischaemic events among those who initiated DOACs at day 14 (group 4).

When estimating which timing groups were optimal for treatment initiation, the posterior probabilities indicated that initiating DOACs sooner rather than later within the first 2 weeks after stroke onset may lead to better outcomes. The posterior probability for being the optimal day for treatment initiation was 41 percent for group 1, 26 percent for group 2, 17 percent for group 3, and 15 percent for group 4.

Three recent European randomized clinical trials have also shown that earlier initiation of DOACs for secondary stroke prevention is noninferior and may be more favourable than later initiation in terms of the rates of ischaemic and haemorrhagic events. However, the investigators noted that the samples in these trials mostly included patients with milder strokes and the data did not pinpoint a precise day for DOAC initiation that best balances the risks of ischaemic and haemorrhagic events. [Circulation 2022;146:1056-1066; N Engl J Med 2023;388:2411-2421; JAMA Neurol 2024;81:693-702; Lancet 2024;404:1731-1741]

Demonstrating that early initiation of a DOAC is at least noninferior supports commencing treatment while patients are still in the hospital, according to the investigators. This is important, given that in real-world practice, the potential for nonadherence to anticoagulation regimens initiated after hospital discharge is a practical concern, they added.

Of the patients included in the study, 54 were randomly allocated to group 1, 53 to group 2, 46 to group 3, and 47 to group 4. The randomization allocations were adjusted to favour the groups with higher probabilities.

The median National Institutes of Health Stroke Scale score in the entire population was 6.5, and the median lesion diameter was 3.1 cm. Baseline characteristics were generally similar among the patient groups. Apixaban was the DOAC prescribed to 89 percent of the patients.

“The current study is the first randomized clinical trial including US patients with AF-related ischaemic stroke assessing when to initiate a DOAC and the first to apply a response-adaptive randomization strategy to the question of delay to initiate a treatment,” the investigators said.

“The results regarding the optimal day to begin treatment were inconclusive but may inform the design of future, larger trials to identify a superior day to initiate use of a DOAC within the early period after stroke onset,” they added.