Early initiation of direct oral anticoagulants after acute stroke with atrial fibrillation is at least as good as later initiation

Reference

Oldgren J, Asberg S, Hijazi Z, et al, for the National TIMING Collaborators. Early versus delayed non–vitamin k antagonist oral anticoagulant therapy after acute ischemic stroke in atrial fibrillation (TIMING): a registry-based randomized controlled noninferiority study. Circulation 2022;146(14):1056-1066.

Synopsis

The balance of benefits and harms for early versus late initiation of anticoagulation in patients with acute stroke is unclear, as the risk of both hemorrhage and recurrent ischemic stroke may be higher in the early phase (0 to 4 days). This Swedish study used a stroke registry to identify 888 patients with acute stroke (< 72 hours) and atrial fibrillation who had no contraindications to taking a direct oral anticoagulant (DOAC). Eligible patients had not been taking a DOAC prior to the stroke or had their DOAC therapy interrupted for 2 or more days prior to the stroke. At baseline, the patients' mean age was 78 years, 46% were women, the mean National Institutes of Health Stroke Scale score was 6 (moderate severity stroke), and approximately half had atrial fibrillation that was previously known. Groups were balanced at baseline and analysis was by intention to treat. Patients were randomized to receive early initiation of a DOAC at 0 to 4 days (mean initiation: day 3), or late initiation between 5 and 10 days (mean initiation: day 5). Physicians could choose the DOAC: 55% of patients received apixaban, 26% received dabigatran, and 13% received rivaroxaban. The primary composite of new ischemic stroke, symptomatic intracranial hemorrhage, or death occurred less often in the early start group (6.9% vs 8.7%) and, although noninferior, this difference was not significantly lower (superior). A numerical reduction was seen for both ischemic stroke and all-cause mortality, though these was also not statistically significant (there were no intracerebral hemorrhages in either group). An important omission is the lack of reporting of functional outcomes.