Objective:

To evaluate safety of early initiation of DOACs after ischemic stroke in patients with atrial fibrillation

Background:

Large Randomized Clinical Trials (RCTs) have established the superiority of Direct oral anticoagulants (DOACs) over vitamin-K antagonists in atrial fibrillation (AF) related to Acute Ischemic stroke (AIS). However,the data regarding outcomes of early versus late administration of DOACs is limited.

Design/Methods:

The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards were followed for this systematic review and meta-analysis. Our search strategy used the Population (AF-related AIS patients taking DOACs), Intervention (early anticoagulation; before 3-4 days), Comparison(late anticoagulation; after 3-4 days), Outcomes and Study type (PICOS) question format. The outcomes of interest were Intracranial hemorrhage (ICH), ischemic stroke and all-cause mortality. The data was pooled using the Mantel-Haenszel random effect model and the Higgins I2 test was used to determine the heterogeneity in each analysis.

Results:

After the database search and study screening, 15 studies were selected. However, only 3 prospective cohorts and 1 RCT were eligible for final analysis. All four eligible studies were of good quality (the Newcastle Ottawa Scale and Cochrane Risk of Bias tool 2). Of the 1831 patients who received DOACs in A-F related AIS, 966 were given DOACs before 3-4 days, and 865 received them after 3-4 days. The adverse event of ICH  (RR 0.65 [95% CI: 0.41 - 1.01] p = 0.06, I2  = 0%) was similar in both early and late groups. No significant difference in Risk of Ischemic stroke (RR 0.67 [95% CI: 0.36 - 1.24] p = 0.20, I2 = 22%) and all-cause mortality (RR 0.72 [95% CI: 0.45 - 1.17] p = 0.19, I2 = 0%) were noted between the two groups.

Conclusions:

Our meta-analysis shows that starting DOAC therapy 3-4 days before ischemic stroke does not increase the risk of intracranial hemorrhage or affect all-cause mortality rates.