Early anticoagulation after ischemic stroke is a safe strategy (ELAN)

Reference

Fischer U, Koga M, Strbian D, et al, for the ELAN Investigators. Early versus later anticoagulation for stroke with atrial fibrillation. N Engl J Med 2023;388(26):2411-2421.

Synopsis

The optimal time to initiate anticoagulation after an acute ischemic stroke is unclear, with some guidelines recommending the “1-3-6-12-day rule” (initiation of anticoagulation 1, 3, 6, and 12 days following a transient ischemic attack, minor stroke, moderate stroke, and major stroke, respectively). In this study, investigators randomized patients with acute ischemic stroke and atrial fibrillation to either early or later initiation of anticoagulation with a direct oral anticoagulant (DOAC). Patients already using therapeutic anticoagulation were excluded. In the early group (n = 1006), DOACs were started within 48 hours of stroke onset for patients with minor or moderate strokes, and on day 6 or 7 after major strokes. In the later group (n = 1007), the 1-3-6-12-day rule was followed. The most common DOAC was apixaban, used in approximately two-thirds of the study patients. Stroke severity was defined using imaging-based criteria. The 2 groups were similar at baseline: median age was 77 years, 45% of participants were female, and there was a similar distribution of stroke severity (37% minor stroke, 40% moderate, and 23% major). The median National Institutes of Health Stroke Scale score at randomization was 3. The study was not designed to test superiority or noninferiority of early versus later anticoagulation, but rather to estimate the treatment effect of early initiation and the degree of precision of this estimate. The primary composite outcome was recurrent ischemic stroke, systemic embolism, major extracranial bleed, symptomatic intracranial bleed, or vascular death within 30 days after randomization. This occurred less frequently in the early group (2.9% vs 4.1%), ranging from 2.8 percentage points lower to 0.5 percentage points higher than the later group. Moreover, the early group had fewer recurrent ischemic strokes (1.4% vs 2.5%), while symptomatic intracranial bleeds were uncommon in both groups (0.2%), suggesting that early initiation may be a safe and effective treatment approach for these patients.