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Through a single-center retrospective cohort study of acute ischemic stroke (AIS) patients receiving secondary prevention with indobufen, clopidogrel, cilostazol, or aspirin as monotherapy or dual therapy, we aim to compare the real-world effectiveness and safety of these four antiplatelet regimens. Through closely tracking the recurrence of stroke (including ischemic and hemorrhagic stroke) and bleeding events (GUSTO-defined) within one year of treatment, we evaluate the association between each antiplatelet agent and the risk of stroke recurrence, thereby providing critical evidence to guide individualized antiplatelet therapy in AIS patients.
Stroke is the second leading cause of death and the third leading cause of disability worldwide, with a 5%-10% one-year recurrence rate after acute ischemic stroke (AIS), making effective secondary prevention critical. Indobufen, aspirin, clopidogrel, and cilostazol-as monotherapy or in combination-constitute the main antiplatelet strategies for secondary prevention of ischemic stroke. Guidelines recommend early clopidogrel-aspirin dual therapy for mild stroke or TIA, while aspirin remains standard for moderate-to-severe cases, though it carries gastrointestinal and bleeding risks. Clopidogrel may be resistant due to CYP2C19 loss-of-function alleles in Asian populations. Cilostazol may be suitable for patients with CYP2C19-deficiency but has an uncertain intracranial bleeding risk. Indobufen, a reversible COX inhibitor, offers lower bleeding risk and fewer gastrointestinal adverse effects, yet lacks large-scale head-to-head trials against the other agents. Thus, real-world evidence to guide optimal antiplatelet selection for diverse ischemic stroke patients is lacking. This study aims to compare the effectiveness and safety of these four agents (monotherapy or guideline-recommended dual therapy) for secondary prevention of ischemic stroke, providing hypothesis-generating evidence for future prospective research.
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| indubufen, aspirin, clopidogrel, cilostazol | Drug | Dosage, Frequency: Indobufen (200 mg twice daily); Aspirin (100 mg once daily); Cilostazol (100 mg twice daily); Clopidogrel (75 mg once daily). Dual antiplatelet therapy (DAPT) with two of these agents was permitted if clinically indicated, as per the treating physician's judgment. |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of composite events, including any new stroke or bleeding events | Stroke includes any ischemic/hemorrhagic stroke. Bleeding events were defined in accordance with the Global Utilization Of Streptokinase And TPA For Occluded Arteries (GUSTO) definition for bleeding. | Within 1 year of treatment |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of new cardiovascular events and death | any stroke/ myocardial infarction/ cardiovascular death | Within 1 year |
| GUSTO-defined bleeding events of all grades | GUSTO-defined bleeding events include intracranial hemorrhage, clinically significant gastrointestinal bleeding, and other specified types of bleeding. |
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Inclusion Criteria:
Exclusion Criteria:
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The study population mainly includes patients who meet the diagnostic criteria for acute ischemic stroke (AIS), are aged over 18 years, hospitalized in the Department of Neurology, Nanfang Hospital, Southern Medical University, between January 2020 and December 2025, received one of the following as a secondary prevention regimen within 7 days after discharge, and have follow-up records at 1 year after treatment initiation. Patients with long-term anticoagulant therapy at baseline, history of hemorrhagic stroke or active bleeding, or severe hepatic or renal dysfunction are excluded.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Jia Yin | Contact | 13802964883 | jiajiayin@139.com | |
| Jiayin Chen | Contact | 13337523808 | liuqiruismu@gmail.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Nanfang Hospital,Southern Medical University Recruiting | Guangzhou | Guangdong | 510515 | China |
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| ID | Term |
|---|---|
| D000083242 | Ischemic Stroke |
| ID | Term |
|---|---|
| D020521 | Stroke |
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| ID | Term |
|---|---|
| D001241 | Aspirin |
| D000077144 | Clopidogrel |
| D000077407 | Cilostazol |
| ID | Term |
|---|---|
| D012459 | Salicylates |
| D062385 | Hydroxybenzoates |
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
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Blood
| Within 1 year |
| National Institutes of Health Stroke Scale (NHISS) score | The NIHSS score is commonly used to assess the degree of neurological impairment in patients with acute stroke. The NIHSS consists of 11 items, with a total score ranging from 0 to 42. Each item has different scoring criteria, typically ranging from 0 (normal) to 4 (most severe) | Within 1 year of treatment |
| Modified Rankin Scale ( mRS ) score | The MRS score is primarily used to measure the degree of disability and daily living ability of patients. The MRS score ranges from 0 to 6, with a total of 7 levels. The higher the score, the more severe the disability and the worse the prognosis. | Within 1 year of treatment |
| Barthel Index | The Barthel Index is a standardized scale widely used to assess patients' activities of daily living (ADL), covering ten basic functional items including feeding, bathing, dressing, toileting, bowel and bladder control, bed-to-chair transfer, walking, and stair climbing. Total scores range from 0 to 100, with higher scores indicating greater independence and better self-care ability. In stroke research, the Barthel Index is commonly used to evaluate neurological recovery and long-term functional outcomes. | Within 1 year of treatment |
| Drug-related adverse events | Drug-related adverse events include gastrointestinal discomfort, rash, abnormal liver function, etc. | Within 1 year of treatment |
| D009422 |
| Nervous System Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D006841 |
| Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D013988 | Ticlopidine |
| D058924 | Thienopyridines |
| D013876 | Thiophenes |
| D013457 | Sulfur Compounds |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D013777 | Tetrazoles |
| D001393 | Azoles |
| D011804 | Quinolines |