Prevalence and Effect of Cerebral Small Vessel Disease in Stroke Patients With Aspirin Treatment Failure-A Hospital-Based Stroke Secondary Prevention Registry

Ping-Song Chou; Pi-Shan Sung; Chi-Hung Liu; Yueh-Feng Sung; Ray-Chang Tzeng; Chun-Pai Yang; Chi-Hsun Lien; Helen L Po; Shang-Chang Ho; Yi-Te Tsai; Tsang-Shan Chen; Shey-Lin Wu; Han-Hwa Hu; A-Ching Chao

doi:10.3389/fneur.2021.645444

Prevalence and Effect of Cerebral Small Vessel Disease in Stroke Patients With Aspirin Treatment Failure-A Hospital-Based Stroke Secondary Prevention Registry

Front Neurol. 2021 Apr 13:12:645444. doi: 10.3389/fneur.2021.645444. eCollection 2021.

Authors

Ping-Song Chou^{1

2}, Pi-Shan Sung³, Chi-Hung Liu^{4

5}, Yueh-Feng Sung⁶, Ray-Chang Tzeng⁷, Chun-Pai Yang^{8

9}, Chi-Hsun Lien¹⁰, Helen L Po¹¹, Shang-Chang Ho⁸, Yi-Te Tsai¹², Tsang-Shan Chen¹³, Shey-Lin Wu¹⁴, Han-Hwa Hu^{15

16

17}, A-Ching Chao^{1

2}

Affiliations

¹ Department of Neurology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
² Department of Neurology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
³ Department of Neurology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
⁴ Department of Neurology, Stroke Center, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan.
⁵ College of Medicine, Chang Gung University, Taoyuan, Taiwan.
⁶ Department of Neurology, National Defense Medical Center, Tri-Service General Hospital, Taipei, Taiwan.
⁷ Department of Neurology, Tainan Municipal Hospital (Managed by Show Chwan Medical Care Corporation), Tainan, Taiwan.
⁸ Department of Neurology, Kuang Tien General Hospital, Taichung, Taiwan.
⁹ Department of Nutrition, Huang-Kuang University, Taichung, Taiwan.
¹⁰ Department of Neurology, Tungs' Taichung Metro Harbor Hospital, Taichung, Taiwan.
¹¹ Department of Neurology, Stroke Center, MacKay Memorial Hospital, Taipei, Taiwan.
¹² Department of Neurology, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan.
¹³ Department of Neurology, Sin-Lau Hospital, The Presbyterian Church of Taiwan, Tainan, Taiwan.
¹⁴ Department of Neurology of Changhua Christian Hospital, Changhua, Taiwan.
¹⁵ Department of Neurology, Taipei Medical University-Shaung Ho Hospital, Taipei, Taiwan.
¹⁶ Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
¹⁷ Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China.

Abstract

Background: Breakthrough strokes during treatment with aspirin, termed clinical aspirin treatment failure (ATF), is common in clinical practice. The burden of cerebral small vessel disease (SVD) is associated with an increased recurrent ischemic stroke risk. However, the association between SVD and ATF remains unclear. This study investigated the prevalence and clinical characteristics of SVD in stroke patients with ATF. Methods: Data from a prospective, and multicenter stroke with ATF registry established in 2018 in Taiwan were used, and 300 patients who developed ischemic stroke concurrent with regular use of aspirin were enrolled. White matter lesions (WMLs) and cerebral microbleeds (CMBs) were identified using the Fazekas scale and Microbleed Anatomical Rating Scale, respectively. Demographic data, cardiovascular comorbidities, and index stroke characteristics of patients with different WML and CMB severities were compared. Logistic regression analyses were performed to explore the factors independently associated with outcomes after ATF. Results: The mean patient age was 69.5 ± 11.8 years, and 70.0% of patients were men. Among all patients, periventricular WML (PVWML), deep WML (DWML), and CMB prevalence was 93.3, 90.0, and 52.5%, respectively. Furthermore, 46.0% of the index strokes were small vessel occlusions. Severe PVWMLs and DWMLs were significantly associated with high CMB burdens. Patients with moderate-to-severe PVWMLs and DWMLs were significantly older and had higher cardiovascular comorbidity prevalence than did patients with no or mild WMLs. Moreover, patients with favorable outcomes exhibited significantly low prevalence of severe PVWMLs (p = 0.001) and DWMLs (p = 0.001). After logistic regression was applied, severe WMLs predicted less favorable outcomes independently, compared with those with no to moderate PVWMLs and DWMLs [odds ratio (OR), 0.47; 95% confidence interval (CI), 0.25-0.87 for severe PVWMLs; OR, 0.40; 95% CI, 0.21-0.79 for severe DWMLs]. Conclusions: SVD is common in stroke patients with ATF. PVWMLs and DWMLs are independently associated with functional outcomes in stroke patients with ATF. The burden of SVD should be considered in future antiplatelet strategies for stroke patients after ATF.

Keywords: aspirin treatment failure; cerebral small vessel disease; microbleed; stroke; white matter lesion.