Statin and dual antiplatelet therapy for the prevention of early neurological deterioration and recurrent stroke in branch atheromatous disease: a protocol for a prospective single-arm study using a historical control for comparison

IntroductionBranch atheromatous disease (BAD) contributes to small-vessel occlusion in cases of occlusion or stenosis of large calibre penetrating arteries, and it is associated with a higher possibility of early neurological deterioration (END) and recurrent stroke in acute ischaemic stroke. As the pathology of BAD is due to atherosclerosis, we postulate that early intensive medical treatment with dual antiplatelet therapy (DAPT) and high-intensity statins may prevent END and recurrent stroke in acute small subcortical infarction caused by BAD.Methods and analysisIn this prospective, single-centre, open-label, non-randomised, single-arm study using a historical control, we will compare early DAPT and high-intensity statin treatment with a historical control group of patients with BAD who were treated with single antiplatelet therapy without high-intensity statin treatment. Patients will be eligible for enrolment if they are admitted for acute ischaemic stroke within 24 hours, have a National Institutes of Health Stroke Scale (NIHSS) score of 1–8 and are diagnosed with BAD by MRI. Patients will take aspirin, clopidogrel and high-intensity statins (atorvastatin or rosuvastatin) within 24 hours of stroke onset, followed by aspirin or clopidogrel alone from day 22. The primary endpoint is the percentage of patients who develop END within 7 days of stroke onset (defined as an increase in the NIHSS score ≥2 points) and recurrent stroke within 30 days. The total sample sizes will be 138 for the intervention group and 277 for the control group. A historical control group will be drawn from previous prospective observation studies.Ethics and disseminationThe protocol of this study has been approved by the Institutional Review Board of Chang Gung Memorial Hospital (202001386A3). All participants will have to sign and date an informed consent form. The findings arising from this study will be disseminated in peer-reviewed journals and academic conferences.Trial registration numberNCT04824911.

Lenticulostriate artery combined with neuroimaging markers of cerebral small vessel disease differentiate the pathogenesis of recent subcortical infarction

Recent subcortical infarction (RSI) in the lenticulostriate artery (LSA) territory with a non-stenotic middle cerebral artery is a heterogeneous entity. We aimed to investigate the role of LSA combined with neuroimaging markers of cerebral small vessel disease (CSVD) in differentiating the pathogenic subtypes of RSI by whole-brain vessel-wall magnetic resonance imaging (WB-VWI). Fifty-two RSI patients without relevant middle cerebral artery (MCA) stenosis on magnetic resonance angiography were prospectively enrolled. RSI was dichotomized as branch atheromatous disease (BAD; a culprit plaque located adjacent to the LSA origin) (n = 34) and CSVD-related lacunar infarction (CSVD-related LI; without plaque or plaque located distal to the LSA origin) (n = 18). Logistic regression analysis showed lacunes (odds ratio [OR] 9.68, 95% confidence interval [CI] 1.71–54.72; P = 0.010) and smaller number of LSA branches (OR 0.59, 95% CI 0.36–0.96; P = 0.034) were associated with of BAD, whereas severe deep white matter hyperintensities (DWMH) (OR 0.11, 95% CI 0.02–0.71; P = 0.021) was associated with CSVD-related LI. In conclusion, the LSA branches combined with lacunes and severe DWMH may delineate subtypes of SSI. The WB-VWI technique could be a credible tool for delineating the heterogeneous entity of SSI in the LSA territory.

Early administration of tirofiban after urokinase-mediated intravenous thrombolysis reduces early neurological deterioration in patients with branch atheromatous disease

Objectives To investigate the effects of early administration of tirofiban after intravenous thrombolysis on early neurological deterioration in patients with branch atheromatous disease. Methods We analyzed clinical data from patients with branch atheromatous disease. We enrolled seven cases into the urokinase-only (UO) control group and 10 cases into the urokinase + tirofiban (UT) treatment group. National Institutes of Health Stroke Scale (NIHSS) scores were obtained at admission and on days 3 and 5 after admission. Modified Rankin Scale (mRS) scores were obtained 3 months after admission. Results Significant differences between the UO and UT groups were evident on days 3 and 5 after admission. In the UT group, there was a significant difference between NIHSS scores at admission and on day 5, while there were no significant differences in scores in the UO group. The early neurological deterioration rates were not significantly different between the two groups. However, there were significant differences in these rates at 72 and 120 hours. Both the mRS scores and the prognoses at 3 months differed between the two groups. Conclusion Early administration of tirofiban after urokinase-mediated intravenous thrombolysis reduces early neurological deterioration and improves the long-term prognosis of patients with branch atheromatous disease.

Abstract WP175: Similarities and Differences in Atherothrombosis, Aortogenic Embolism, and Branch Atheromatous Disease

Introduction: Branch atheromatous disease (BAD) and aortogenic embolism (Ao) are categorized as “unclassified” in accordance with “The Trial of Org 10172 in Acute Stroke Treatment (TOAST)” classification; however, their pathophysiology is similar to that of atherothrombosis (AT). We compared these categories of ischemic cerebrovascular disease (iCVD). Methods: A consecutive series of 1,079 patients with iCVD 7 days within onset were included. According to TOAST classification, 180 (16.7%), 159 (14.7%), 251 (23.3%), and 489 (45.3%) patients were classified as AT, lacunar, cardiogenic embolism, and unclassified, respectively. Of the unclassified, 145 and 82 patients were re-classified as Ao and BAD, respectively. Results: Mean age was 75.3, 75.7, and 73.0 years in AT, Ao, and BAD, respectively. Male predominance was most apparent in AT (62.6%), followed by BAD (54.7%) and Ao (54.6%). Prevalence of hypertension, diabetes mellitus, and dyslipidemia was 80.7%, 39.4%, and 53.6% in AT, 83.8%, 30.5%, and 53.9% in Ao, and 74.7%, 33.3%, and 57.3% in BAD, respectively. Hemodialysis was more common in Ao (6.7%) than in BAD (2.7%) and AT (0.7%). Median (IQR) of National Institutes of Health Stroke Scale score on admission and at discharge was 3 (1-6) and 1 (1-3) in AT, 2 (0-4) and 0 (0-2) in Ao, and 5 (3-6) and 2 (1-5) in BAD, respectively. Neurological deterioration was more frequent in BAD (30.7%) than in AT (16.1%) and Ao (2.6%). Median (IQR) of modified Rankin scale (mRS) prior to iCVD and at discharge was 0 (1-2) and 2 (0-4) in AT, 0 (0-1) and 1 (0-2.25) in Ao, and 0 (0-1) and 2 (1-4) in BAD, respectively. The percentage of patients with mRS 2 or better prior to onset and at discharge was 83.2% and 63.9% in AT, 88.3% and 75.3% in Ao, and 89.3% and 58.7% in BAD, respectively. Recurrence of iCVD at 3 months after onset was more frequent in AT (12.9%) than in Ao (9.7%) and BAD (5.3%). Conclusions: Ao and BAD have many similarities with AT, but there are some differences. In Ao, symptoms were often mild and rarely worsened, but with recurrence of up to 10%. There were many dialysis patients in Ao. Worsening was observed in more than 30% of patients, and outcomes were often poor, but recurrences were few in BAD patients.

Branch atheromatous disease diagnosed as embolic stroke of undetermined source: A sub-analysis of NAVIGATE ESUS

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.