Article Impact Level: HIGH Data Quality: STRONG Summary of New England Journal of Medicine, NEJMoa2303048. https://doi.org/10.1056/NEJMoa2303048 Dr. Urs Fischer et al.
Points
- The study aimed to evaluate the impact of early initiation of direct oral anticoagulants (DOACs) compared to later initiation in patients with atrial fibrillation after an acute ischemic stroke.
- A total of 2013 participants were randomly assigned to receive either early or later anticoagulation, with assessors unaware of the group assignments.
- The primary outcome measured the occurrence of recurrent ischemic stroke, systemic embolism, major extracranial bleeding, symptomatic intracranial hemorrhage, or vascular death within 30 days after randomization.
- Within 30 days, the incidence of the primary outcome event was 2.9% in the early-treatment group and 4.1% in the later-treatment group, resulting in a risk difference of -1.18 percentage points (95% CI, -2.84 to 0.47).
- Recurrent ischemic stroke was observed in 1.4% of the early-treatment group and 2.5% of the later-treatment group within 30 days and 1.9% and 3.1%, respectively, by 90 days.
Summary
This research paper aimed to assess the impact of early initiation of direct oral anticoagulants (DOACs) compared to later initiation in individuals with atrial fibrillation who had experienced an acute ischemic stroke. The investigator-initiated, open-label trial study involved 2013 participants from 103 sites across 15 countries. These participants were randomly assigned in a 1:1 ratio to either early anticoagulation (within 48 hours after a minor or moderate stroke or on day 6 or 7 after a significant stroke) or later anticoagulation (day 3 or 4 after a minor stroke, day 6 or 7 after a moderate stroke, or day 12, 13, or 14 after a major stroke). The primary outcome measured was a composite of recurrent ischemic stroke, systemic embolism, major extracranial bleeding, symptomatic intracranial hemorrhage, or vascular death within 30 days after randomization. Secondary outcomes included the components of the primary outcome at both 30 and 90 days.
The study population comprised 37% of participants with minor stroke, 40% with moderate stroke, and 23% with significant stroke. Among the 2013 participants, 1006 were assigned to the early anticoagulation group, while 1007 were assigned to the latter anticoagulation group. The primary outcome event occurred in 2.9% of the early-treatment group and 4.1% of the later-treatment group within 30 days, resulting in a risk difference of -1.18 percentage points (95% confidence interval [CI], -2.84 to 0.47). Recurrent ischemic stroke was observed in 1.4% of the early-treatment group and 2.5% of the later-treatment group within 30 days (odds ratio, 0.57; 95% CI, 0.29 to 1.07) and in 1.9% and 3.1% respectively, by 90 days (odds ratio, 0.60; 95% CI, 0.33 to 1.06). Symptomatic intracranial hemorrhage occurred in 0.2% of participants in both groups by 30 days.
Based on the trial results, the incidence of recurrent ischemic stroke, systemic embolism, major extracranial bleeding, symptomatic intracranial hemorrhage, or vascular death within 30 days was estimated to range from 2.8 percentage points lower to 0.5 percentage points higher (based on the 95% confidence interval) with early initiation of DOACs compared to later initiation. These findings contribute valuable insights into determining the optimal timing for initiating DOACs in individuals with atrial fibrillation after experiencing an acute ischemic stroke.
Link to the article: https://www.nejm.org/doi/full/10.1056/NEJMoa2303048
References 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. N., Aguiar De Sousa, D., Bornstein, N. M., … Dawson, J. (2023). Early versus later anticoagulation for stroke with atrial fibrillation. New England Journal of Medicine, NEJMoa2303048. https://doi.org/10.1056/NEJMoa2303048
