Use of oral anticoagulation for people with atrial fibrillation post-stroke and associations with recurrent stroke and mortality: a systematic review

Abstract Introduction Current guidelines recommend oral anticoagulation (OAC) to reduce recurrent stroke risk for people with atrial fibrillation (AF); however, outcomes for post-stroke AF patients receiving different types of anticoagulants and optimal timing of anticoagulation in this population remains unclear. Purpose The objective of this systematic review was to summarise observational study data reporting associations between OAC use and risk of mortality, recurrent stroke, and major bleeding within post-stroke AF populations. Methods SCOPUS and OVID Medline databases were searched from inception to 02/11/2020. Studies were limited to publications in the English language post-2012. Observational studies, including case-control and cohort studies were eligible for inclusion. The outcomes examined were all-cause mortality, recurrent stroke and major bleeding. Screening and risk of bias assessment with the Newcastle-Ottawa scale were completed independently by two reviewers. Data extraction was completed by one reviewer and checked by a second. The review was registered on PROSPERO: CRD42020221105. Results Searches identified 3803 studies; 29 studies were eligible for inclusion. Variations between studies including time of OAC initiation, types of OACs used, and length of follow-up meant a meta-analysis was not possible. Four of six studies reporting effect measures of pre-admission or post-stroke OAC use found significant associations with reduced all-cause post-stroke mortality compared to no OAC use (Figure 1A). One study reported lower recurrent stroke rates in patients with no preadmission OAC use compared to preadmission OAC use (2.9% vs. 5.3%; adjusted hazard ratio (aHR) 1.50, 95% confidence interval [CI] 1.02–2.21). A separate study found post-stroke OAC use resulted in a non-significant lower stroke recurrence rate compared to no post-stroke OAC use (3.7% vs. 4.3%; p=0.9). Eight studies examined non-vitamin K antagonist OACs (NOACs) compared to warfarin; five demonstrated significant associations between post-stroke NOAC use and improved outcomes such as post-stroke mortality (Figure 1B). Two studies examined post-stroke OAC therapy timing; both suggested OAC initiation within 4 days of the index event was associated with reduced all-cause mortality (4.5% and 0.6% vs. 8.7% and 3.1%) and recurrent stroke rates (9.4% and 0.8% vs. 10.5% and 1.6%). One study reported non-significant increased major bleeding rates for earlier OAC initiation (2.7% vs. 2.2%; aHR 1.39, 95% CI 0.42–4.60). Overall, the results were consistent with previously published randomised controlled trials. Conclusions Evidence from observational studies suggest that the overall benefit of NOACs in reducing recurrent stroke and post-stroke mortality outweighs the risk of major bleeding in post-stroke AF patients. There is a need for further studies to evaluate the optimum timing of post-stroke anticoagulation initiation and management differences in patients with AF. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): The project is supported by the MRes programme in the Institute of Life Course and Medical Sciences at The University of Liverpool. All-Cause Mortality Forest Plots