Early anticoagulation can be safely initiated for stroke with atrial fibrillation, according to the findings of a new study.
The effects of early versus later initiation of direct oral anticoagulants (DOACs) in atrial fibrillation (AF) patients after an acute ischemic stroke are unclear. Early initiation may increase the risk of bleeding, whereas later initiation may increase the risk of stroke recurrence.
A study in The New England Journal of Medicine compared the safety and efficacy of early and late initiation of DOACs in post-ischemic stroke patients with AF.
Study Population
Of the 2013 participants, 1006 were assigned to early anticoagulation (within 48 hours of a minor or moderate stroke; day 6 or 7 after a major stroke) and 1007 to later anticoagulation (day 3 or 4 after a minor stroke; day 6 or 7 after a moderate stroke; day 12, 13, or 14 after a major stroke). Baseline characteristics were similar in both groups. The median age was 77 years, and 45% were female.
Based on imaging criteria, 38% of the early treatment group and 37% of later treatment group participants had experienced a minor stroke; 40% and 39%, respectively, had experienced a moderate stroke; and 23% in each group had experienced a major stroke.
Comparison of Early and Later Anticoagulation Treatment Outcomes
The primary outcome was a composite of recurrent ischemic stroke, systemic embolism, symptomatic intracranial hemorrhage, major extracranial bleeding, or vascular death within 30 days of randomization. Out of 1975 participants, a primary outcome event occurred in 29 (2.9%) in the early treatment group and 41 (4.1%) in the later treatment group. The estimated odds ratio for a primary outcome event was 0.70 (95% confidence interval: 0.44–1.14) in the early treatment group versus the later treatment group, while the derived risk difference was −1.18 percentage points (95%CI: −2.84–0.47).
Secondary Outcomes Show Favorable Trends in Early Treatment Groups
The secondary outcomes at 30 and 90 days included recurrent ischemic stroke, systemic embolism, symptomatic intracranial hemorrhage, major extracranial bleeding, vascular death, death from any cause, non-major bleeding, a binary outcome of a score of 0–2 versus 3–6 on the modified Rankin scale, and an ordinal shift in score distribution on the modified Rankin scale between the groups.
By day 30, major extracranial bleeding occurred in three (0.3%) early treatment group and five (0.5%) later treatment group participants (odds ratio: 0.63, 95%CI: 0.15–2.38), symptomatic intracranial hemorrhage occurred in two participants (0.2%) in both groups (OR: 1.02, 95%CI: 0.16–6.59), and recurrent ischemic stroke occurred in 14 (1.4%) early treatment group and 25 (2.5%) later treatment group participants (OR: 0.57, 95%CI: 0.29–1.07).
By day 90, recurrent ischemic stroke occurred in 18 participants (cumulative rate: 1.9%) in the early treatment group and 30 participants (3.1%) in the later-treatment group (OR: 0.60, 95%CI: 0.33–1.06).
Early Direct Oral Anticoagulant Initiation Deemed Safe
The composite outcome incidence by day 30 was estimated to range from 2.8 percentage points lower to 0.5 percentage points higher (based on the 95%CI) with early use of DOACs than with later use. Analysis indicated a 98% probability that early initiation of DOACs would increase the risk of a primary outcome event by no more than 0.5 percentage points. Early treatment can, therefore, be initiated if indicated or desired.
Source
Fischer, U., Koga, M., Strbian, D., Branca, M., Abend, S., Trelle, S., Paciaroni, M., Thomalla, G., Michel, P., Nedeltchev, K., Bonati, L. H., Ntaios, G., Gattringer, T., Sandset, E. C., Kelly, P., Lemmens, R., Sylaja, P., De Sousa, D. A., Bornstein, N. M., . . . Dawson, J. (2023). Early versus Later Anticoagulation for Stroke with Atrial Fibrillation. The New England Journal of Medicine, 388(26), 2411–2421. https://doi.org/10.1056/nejmoa2303048
