Impact Of Novel Oral Anticoagulant Use On Secular Trend Of Vascular Events Or Death After Atrial Fibrillation-related Acute Ischemic Stroke

Introduction: Now novel oral anticoagulants (NOAC) are strongly recommended for secondary stroke prevention in patients with atrial fibrillation (AF). However, it remains unclear to what extent the introduction of NOACs improved clinical outcomes in real-world practice. Methods: Using a nationwide prospective multi-center stroke registry database, we identified consecutive AIS patients with AF enrolled between Jan 2011 and Dec 2019, and analyzed one-year clinical events and NOAC prescription at discharge. The primary outcome was the composite of stroke, myocardial infarction, and all-cause death. To assess the mediation effect of NOAC on the outcomes, we performed natural effect models according to the calendar year. The exposure-mediator analysis, exposure-outcome analysis, and mediator-outcome analysis were performed using multivariate regression analysis according to the characteristics of the variables. Results: We analyzed 12,500 patients (mean age, 74.4 years; 51.3% male; median NIHSS at presentation, 8). From 2011 to 2019, the cumulative one-year incidence of the primary composite outcome (28.3% to 22.1%), all-cause mortality (23.8% to 17.9%), and stroke recurrence (8.3% to 5.1%) significantly decreased, while the NOAC prescription rate at discharge increased (0% to 75.6%). One-year increase in the calendar year was independently associated with a delayed occurrence of primary composite outcomes (Step 1: adjusted Time Ratio (aTR), 1.10; 95% confidence interval, 1.07-1.14) and with an increased NOAC prescription rate (Step 2: adjusted odds ratio, 2.20; 2.14-2.27). Increase in the NOAC prescription rate was significantly associated with the delayed occurrence of primary composite outcome (Step 3: aTR, 3.80; 3.15-4.58). However, after controlling for the NOAC prescription rate (mediator), the calendar year was no longer associated with the primary composite outcomes. (Step 4: aTR, 0.78; 95% CI 0.60-1.03). Thus, our results indicate full mediation of NOAC prescription in the association between the calendar year and primary composite outcomes. Conclusion: The reduced risk of major vascular events or death over time in AIS patients with AF was fully mediated by the increase in NOAC use.