DOI: 10.1161/strokeaha.123.044487 ISSN: 0039-2499

Secular Trends in Outcomes and Impact of Novel Oral Anticoagulants in Atrial Fibrillation–Related Acute Ischemic Stroke

Minwoo Lee, Byung-Chul Lee, Kyung-Ho Yu, Mi-Sun Oh, Beom Joon Kim, Jun Yup Kim, Jihoon Kang, Keon-Joo Lee, Do Yeon Kim, Jong-Moo Park, Kyusik Kang, Tai Hwan Park, Kyung Bok Lee, Keun-Sik Hong, Hong-Kyun Park, Yong-Jin Cho, Dong-Eog Kim, Soo Joo Lee, Jae Guk Kim, Jun Lee, Jae-Kwan Cha, Dae-Hyun Kim, Joon-Tae Kim, Kang-Ho Choi, Jay Chol Choi, Sung-il Sohn, Jeong-Ho Hong, Sang-hwa Lee, Chulho Kim, Dong-Ick Shin, Kyu Sun Yum, Juneyoung Lee, Ji Sung Lee, Philip B. Gorelick, Hee-Joon Bae,
  • Advanced and Specialized Nursing
  • Cardiology and Cardiovascular Medicine
  • Neurology (clinical)


Novel oral anticoagulants (NOACs) are currently recommended for the secondary prevention of stroke in patients with acute ischemic stroke (AIS) accompanied by atrial fibrillation (AF). However, the impact of NOACs on clinical outcomes in real-world practice remains ambiguous. This study analyzes the trend of clinical events in patients with AF-related AIS and determines how much the introduction of NOACs has mediated this trend.


We identified patients with AIS and AF between January 2011 and December 2019 using a multicenter stroke registry. Annual rates of NOAC prescriptions and clinical events within 1 year were evaluated. The primary outcome was a composite of recurrent stroke, myocardial infarction, and all-cause mortality. To assess the mediation effect of NOACs on the relationship between the calendar year and these outcomes, we used natural effect models and conducted exposure-mediator, exposure-outcome, and mediator-outcome analyses using multivariable regression models or accelerated failure time models, adjusting for potential confounders.


Among the 12 977 patients with AF-related AIS, 12 500 (average age: 74.4 years; 51.3% male) were analyzed after excluding cases of valvular AF. Between 2011 and 2019, there was a significant decrease in the 1-year incidence of the primary composite outcome from 28.3% to 21.7%, while the NOAC prescription rate increased from 0% to 75.6%. A 1-year increase in the calendar year was independently associated with delayed occurrence of the primary outcome (adjusted time ratio, 1.10 [95% CI, 1.07–1.14]) and increased NOAC prescription (adjusted odds ratio, 2.20 [95% CI, 2.14–2.27]). Increased NOAC prescription was associated with delayed occurrence of the primary outcome (adjusted time ratio, 3.82 [95% CI, 3.17 to 4.61]). Upon controlling for NOAC prescription (mediator), the calendar year no longer influenced the primary outcome (adjusted time ratio, 0.97 [95% CI, 0.94–1.00]). This suggests that NOAC prescription mediates the association between the calendar year and the primary outcome.


Our study highlights a temporal reduction in major clinical events or death in Korean patients with AF-related AIS, mediated by increased NOAC prescription, emphasizing NOAC use in this population.

More from our Archive