{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:23:40Z","timestamp":1790702620636,"version":"4.1.0"},"reference-count":36,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>The prevalence of cerebral small vessel disease (CSVD) imaging markers is high, yet their influence on stroke prognosis remains unclear. This study aimed to estimate the effects of CSVD on the efficacy and safety of clopidogrel+aspirin versus aspirin among patients with minor stroke or high-risk transient ischemic attack.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>This was a post hoc subgroup analysis of the INSPIRES trial (Intensive Statin and Antiplatelet Therapy for Acute High-Risk Intracranial or Extracranial Atherosclerosis), which was a double-blind, placebo-controlled, 2\u00d72 factorial, and randomized clinical trial conducted at 222 centers in China from September 2018 to October 2022. Patients were classified into CSVD score 0 to 2 and CSVD score \u22653 groups based on a modified CSVD burden score without microbleeds. The primary efficacy and safety outcomes were stroke recurrence and moderate-to-severe bleeding risk within 90-day follow-up. We used Cox proportional hazards models to test the treatment-by-CSVD group interaction for stroke and bleeding risk.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              A total of 5126 patients (median age, 65 [57\u201371] years; 3915 [64.2%] males) were enrolled and 2131 (41.57%) had a modified CSVD score \u22653. Patients with CSVD score \u22653 had numerically higher stroke recurrence rate (9.10% versus 8.05%) and lower risk of moderate-to-severe bleeding (0.56% versus 0.80%) than those with CSVD score 0 to 2 within 90 days. Clopidogrel+aspirin versus aspirin reduced stroke recurrence to a similar relative degree in both CSVD score 0 to 2 (adjusted hazard ratio, 0.78 [95% CI, 0.61\u20131.01];\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              =0.06) and CSVD score \u22653 groups (adjusted hazard ratio, 0.82 [95% CI, 0.62\u20131.09];\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              =0.12) with no evidence of statistical interaction (\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              =0.84). Clopidogrel+aspirin versus aspirin increased bleeding risk to a similar relative degree in both CSVD score 0 to 2 (adjusted hazard ratio, 2.83 [95% CI, 1.52\u20135.27];\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              =0.03) and CSVD score \u22653 groups (adjusted hazard ratio, 2.13 [95% CI, 1.08\u20134.19];\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              =0.22) with no statistical interaction (\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              =0.68).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>In this post hoc subgroup analysis, no significant interaction effect was observed between the antiplatelet treatment and the modified CSVD score, suggesting that clopidogrel+aspirin may not provide a significantly different benefit-risk profile across patients with CSVD score 0 to 2 versus CSVD score \u22653.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>REGISTRATION:<\/jats:title>\n            <jats:p>\n              URL:\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n              ; Unique identifier: NCT03635749.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/strokeaha.124.049826","type":"journal-article","created":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T09:00:59Z","timestamp":1744016459000},"page":"1376-1387","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["Does the Burden of CSVD Modify the Efficacy of Dual Antiplatelet Therapy?: A Post Hoc Analysis of the INSPIRES Trial"],"prefix":"10.1161","volume":"56","clinical-trial-number":[{"clinical-trial-number":"nct03635749","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4543-9271","authenticated-orcid":true,"given":"Hang","family":"Li","sequence":"first","affiliation":[{"name":"Department of Neurology, Beijing Tiantan Hospital (H.L., M.C., Y.G., H.Y., Yicong Wang, Y.Y., W.C., Yongjun Wang, Y.P., Yilong Wang), Capital Medical University, China."},{"name":"Department of Geriatrics, Affiliated Dalian Friendship Hospital of Dalian Medical University, Liaoning, China (H.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Neurology, Beijing Tiantan Hospital (H.L., M.C., Y.G., H.Y., Yicong Wang, Y.Y., W.C., Yongjun Wang, Y.P., Yilong Wang), Capital Medical University, China."},{"name":"Department of Neurology, Shunyi District Hospital, Beijing, China (M.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Neurology, Beijing Tiantan Hospital (H.L., M.C., Y.G., H.Y., Yicong Wang, Y.Y., W.C., Yongjun Wang, Y.P., Yilong Wang), Capital Medical University, China."},{"name":"China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University (Y.G., H.Y., Yongjun Wang, Y.P., Yilong Wang)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5190-6345","authenticated-orcid":true,"given":"Hongyi","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Beijing Tiantan Hospital (H.L., M.C., Y.G., H.Y., Yicong Wang, Y.Y., W.C., Yongjun Wang, Y.P., Yilong Wang), Capital Medical University, China."},{"name":"China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University (Y.G., H.Y., Yongjun Wang, Y.P., Yilong Wang)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0271-626X","authenticated-orcid":true,"given":"Yicong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Beijing Tiantan Hospital (H.L., M.C., Y.G., H.Y., Yicong Wang, Y.Y., W.C., Yongjun Wang, Y.P., Yilong Wang), Capital Medical University, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2912-0714","authenticated-orcid":true,"given":"S. Claiborne","family":"Johnston","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of California, San Francisco (S.C.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2734-5132","authenticated-orcid":true,"given":"Philip M.","family":"Bath","sequence":"additional","affiliation":[{"name":"Stroke Trials Unit, Division of Mental Health and Clinical Neuroscience, University of Nottingham, United Kingdom (P.M.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3842-1236","authenticated-orcid":true,"given":"Pierre","family":"Amarenco","sequence":"additional","affiliation":[{"name":"Department of Neurology and Stroke Center, Bichat Hospital, Assistance Publique\u2013H\u00f4pitaux de Paris, University of Paris, France (P.A.)."},{"name":"Population Health Research Institute, McMaster University, Hamilton, Canada (P.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9431-9925","authenticated-orcid":true,"given":"Yingying","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Beijing Tiantan Hospital (H.L., M.C., Y.G., H.Y., Yicong Wang, Y.Y., W.C., Yongjun Wang, Y.P., Yilong Wang), Capital Medical University, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiqi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Beijing Tiantan Hospital (H.L., M.C., Y.G., H.Y., Yicong Wang, Y.Y., W.C., Yongjun Wang, Y.P., Yilong Wang), Capital Medical University, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9976-2341","authenticated-orcid":true,"given":"Yongjun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Beijing Tiantan Hospital (H.L., M.C., Y.G., H.Y., Yicong Wang, Y.Y., W.C., Yongjun Wang, Y.P., Yilong Wang), Capital Medical University, China."},{"name":"Advanced Innovation Center for Human Brain Protection (Yongjun Wang, Yilong Wang), Capital Medical University, China."},{"name":"China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University (Y.G., H.Y., Yongjun Wang, Y.P., Yilong Wang)."},{"name":"National Center for Neurological Disorders, Shanghai, China (Yongjun Wang, Yilong Wang)."},{"name":"Research Unit of Artificial Intelligence in Cerebrovascular Disease, Chinese Academy of Medical Sciences, Beijing, China (Yongjun Wang)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3082-6789","authenticated-orcid":true,"given":"Yuesong","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Beijing Tiantan Hospital (H.L., M.C., Y.G., H.Y., Yicong Wang, Y.Y., W.C., Yongjun Wang, Y.P., Yilong Wang), Capital Medical University, China."},{"name":"China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University (Y.G., H.Y., Yongjun Wang, Y.P., Yilong Wang)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2725-2788","authenticated-orcid":true,"given":"Yilong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Beijing Tiantan Hospital (H.L., M.C., Y.G., H.Y., Yicong Wang, Y.Y., W.C., Yongjun Wang, Y.P., Yilong Wang), Capital Medical University, China."},{"name":"Advanced Innovation Center for Human Brain Protection (Yongjun Wang, Yilong Wang), Capital Medical University, China."},{"name":"Beijing Laboratory of Oral Health (Yilong Wang), Capital Medical University, China."},{"name":"China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University (Y.G., H.Y., Yongjun Wang, Y.P., Yilong Wang)."},{"name":"National Center for Neurological Disorders, Shanghai, China (Yongjun Wang, Yilong Wang)."},{"name":"Chinese Institute for Brain Research, Beijing, China (Yilong 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