Oral Anticoagulation Timing in Patients with Acute Ischaemic Stroke and Atrial Fibrillation

Background and Purpose: Oral anticoagulants (OACs) prevent stroke recurrence and vascular embolism in patients with acute ischaemic stroke (AIS) and atrial fibrillation (AF). Current guidance recommends a “1-3-6-12 day”’ rule to resume OACs after AIS, based mainly on empirical consensus. This study investigated the suitability of guideline-recommended timing for OAC initiation. Methods: To overcome immortal time bias, we emulated a sequence of randomized placebo-controlled trials and constructed 90 propensity score-matched cohorts of 12,307 patients with AF and AIS from 2012 to 2016. We compared the risk of composite effectiveness and safety outcome in the early vs no OAC use group and in the delayed vs no OAC use. Indirect comparison between early and delayed use was conducted using a network meta-analysis. Results: Across the groups of AIS severity, the risks of composite outcome or effectiveness outcome were lower in the OAC use group than the no use group and the risks were similar between the early and delayed use groups. In patients with severe AIS, those receiving early OACs use had an increased risk of safety outcome, with HR of 2.10 (CI: 1.13-3.92) compared with those without OAC use, and HR of 1·44 (CI: 0·99-2·09) compared with those receiving delayed use. Conclusions: In AF patients with severe AIS, early OAC use before the guideline-recommended days appeared to increase the risk of bleeding events, although the OAC initiation time seemed not to affect the risk of serious vascular events. The optimal severity-specific timing for OAC initiation after AIS requires further evaluation