We conducted this review and analysis to assess whether DOACs offer superior outcomes or reduced risks compared with aspirin, warfarin, or placebo in Atrial fibrillation (AF) patients with previous stroke or transient ischemic attack (TIA).

Atrial fibrillation, a prevalent and persistent heart rhythm disorder, significantly increases the risk of stroke, TIA, myocardial infarction (MI), and death.

To identify relevant randomized controlled trials (RCTs), an organized search was performed across EMBASE, PubMed, and Cochrane Central Register of Controlled Trials until April 2025. Risk ratios (RR) and 95% CI range in terms of clinical endpoints assessed the effectiveness of DOACs. Stroke or systemic embolism and intracranial hemorrhage (ICH) were primary efficacy outcomes, whereas ischemic and hemorrhagic strokes, myocardial infarction, and gastrointestinal bleeding were considered secondary outcomes.

Eleven RCTs involving 23,952 AF patients with previous stroke or TIA were included. DOACs were compared with warfarin in six studies and with aspirin or placebo in five studies. Compared to warfarin, DOACs reduced the risk of stroke or systemic embolism (0.86 is RR; [0.76–0.98] 95% CI; P-value = 0.02) and ICH (0.54 is RR; [0.42–0.69] 95% CI; P-value < 0.00001). In comparison to aspirin or placebo, DOACs showed a decline in the risk of stroke (0.41 is RR; [0.29–0.59] 95% CI; P-value = < 0.00001), with a slight increase in ICH risk (1.57 is RR; [0.82–2.99] 95% CI; P-value = 0.17).

Based on this cumulative analysis, the use of DOACs in AF patients with a past occurrence of stroke or TIA is recommended instead of other antithrombotic medications.