Shinichiro Uchiyama1, Kazunori Toyoda2, Kazuo Kitagawa3, Yasushi Okada4, Sebastian Ameriso5, Hardi Mundl6, Scott Berkowitz7, Takashi Yamada8, Yan Yun Liu9, Robert G Hart9. 1. Clinical Research Center for Medicine, International University of Health and Welfare, Center for Brain and Cerebral Vessels, Sanno Hospital and Sanno Medical Center, Tokyo, Japan. 2. National Cerebral and Cardiovascular Center, Osaka, Japan. 3. Department of Neurology, Tokyo Women's Medical University, Tokyo, Japan. 4. National Hospital Organization Kyushu Medical Center, Fukuoka, Japan. 5. Institute for Neurological Research-FLENI, Buenos Aires, Argentina. 6. Bayer AG, Wuppertal, Germany. 7. Bayer U.S. LLC, Pharmaceuticals Clinical Development Thrombosis, Whippany, NJ, USA. 8. Bayer Yakuhin, Ltd., Osaka, Japan. 9. Population Health Research Institute, Hamilton, Canada.
Abstract
BACKGROUND: Branch atheromatous disease (BAD) is distinctive from large and small arterial diseases, which is single subcortical infarction larger than lacunar stroke in the territories of deep perforators without relevant arterial stenosis. BAD meets the current criteria of embolic stroke of undetermined source. We performed an exploratory analysis of BAD in patients recruited to NAVIGATE embolic stroke of undetermined source, a randomized controlled trial to compare rivaroxaban and aspirin in embolic stroke of undetermined source patients. METHODS AND RESULTS: Among 3972 stroke patients in cerebral hemispheres with intracranial arterial imaging, 502 (12.6%) patients met the criteria for BAD. BAD was associated with younger age (years; OR: 0.97, 95% CI: 0.96-0.98), race (Asian; OR: 1.78, 95% CI: 1.44-2.21), region (Eastern Europe; OR: 2.49, 95% CI: 1.87-3.32), and higher National Institute of Health Stroke Scale (OR: 1.17, 95% CI: 1.12-1.22) at randomization. During follow-up, stroke or systemic embolism (2.5%/year vs. 6.2%/year, p = 0.0022), stroke (2.1%/year vs. 6.2%/year, p = 0.0008), and ischemic stroke (2.1%/year vs. 5.9%/year, p = 0.0013) occurred less frequently in BAD than non-BAD patients. There were no differences in annual rates of stroke or systemic embolism (2.5%/year vs. 2.5%/year, HR: 1.01, 95% CI: 0.33-3.14) or major bleeding (1.3%/year vs. 0.8%/year, HR: 1.51, 95% CI: 0.25-9.05) between rivaroxaban and aspirin groups among BAD patients. CONCLUSIONS:BAD was relatively common, especially in Asian and from Eastern Europe among embolic stroke of undetermined source patients. Stroke severity was higher at randomization but recurrence of stroke was fewer in BAD than non-BAD patients. The efficacy and safety of rivaroxaban and aspirin did not differ among BAD patients.
RCT Entities:
BACKGROUND:Branch atheromatous disease (BAD) is distinctive from large and small arterial diseases, which is single subcortical infarction larger than lacunar stroke in the territories of deep perforators without relevant arterial stenosis. BAD meets the current criteria of embolic stroke of undetermined source. We performed an exploratory analysis of BAD in patients recruited to NAVIGATE embolic stroke of undetermined source, a randomized controlled trial to compare rivaroxaban and aspirin in embolic stroke of undetermined source patients. METHODS AND RESULTS: Among 3972 strokepatients in cerebral hemispheres with intracranial arterial imaging, 502 (12.6%) patients met the criteria for BAD. BAD was associated with younger age (years; OR: 0.97, 95% CI: 0.96-0.98), race (Asian; OR: 1.78, 95% CI: 1.44-2.21), region (Eastern Europe; OR: 2.49, 95% CI: 1.87-3.32), and higher National Institute of Health Stroke Scale (OR: 1.17, 95% CI: 1.12-1.22) at randomization. During follow-up, stroke or systemic embolism (2.5%/year vs. 6.2%/year, p = 0.0022), stroke (2.1%/year vs. 6.2%/year, p = 0.0008), and ischemic stroke (2.1%/year vs. 5.9%/year, p = 0.0013) occurred less frequently in BAD than non-BAD patients. There were no differences in annual rates of stroke or systemic embolism (2.5%/year vs. 2.5%/year, HR: 1.01, 95% CI: 0.33-3.14) or major bleeding (1.3%/year vs. 0.8%/year, HR: 1.51, 95% CI: 0.25-9.05) between rivaroxaban and aspirin groups among BAD patients. CONCLUSIONS: BAD was relatively common, especially in Asian and from Eastern Europe among embolic stroke of undetermined source patients. Stroke severity was higher at randomization but recurrence of stroke was fewer in BAD than non-BAD patients. The efficacy and safety of rivaroxaban and aspirin did not differ among BAD patients.