Early noninferior to delayed NOAC initiation after stroke in AF patients

Early initiation of nonvitamin K antagonist oral anticoagulants (NOACs) after acute ischaemic stroke in patients with atrial fibrillation (AF) appears to yield similar outcomes when compared with delayed initiation, as shown in the results of the TIMING* study.

The noninferiority, open-label, blinded endpoint study TIMING was conducted at 34 stroke units using the Swedish Stroke Register. A total of 888 patients were randomized to early (≤4 days; n=450) or delayed (5–10 days; n=438) NOAC initiation, with choice of NOAC at the investigators’ discretion, within 72 hours from stroke onset.

The mean age of the patients was 78.3 years, and 46.2 percent were women, 49.1 percent had previously known AF, and 17.5 percent had prior stroke. All patients completed the 90-day follow-up.

The primary outcome of the composite of recurrent ischaemic stroke, symptomatic intracerebral haemorrhage, or all-cause mortality at 90 days was documented in 31 patients (6.89 percent) in the early NOAC arm and in 38 patients (8.68 percent) in the delayed NOAC arm. The absolute risk difference of −1.79 percent (95 percent CI, −5.31 to 1.74) confirmed the noninferiority of early NOAC initiation to delayed initiation (p=0.004).

When the outcomes were assessed separately, ischaemic stroke rates were slightly lower in the early vs delayed NOAC arm (3.11 percent vs 4.57 percent; risk difference, −1.46 percent, 95 percent CI, −3.98 to 1.07). The same was true for all-cause mortality rates (4.67 percent and 5.71 percent; risk difference, −1.04 percent, 95 percent CI, −3.96 to 1.88).

None of the patients in either arm experienced symptomatic intracerebral haemorrhage.

The finding of numerically lower frequency of ischaemic stroke and death and the absence of symptomatic intracerebral haemorrhages suggests that early initiation of NOAC is safe and should be considered for acute secondary stroke prevention in patients eligible for NOAC treatment, according to researchers.

*Timing of Oral Anticoagulant Therapy in Acute Ischemic Stroke With Atrial Fibrillation