Efficacy and Safety of Indobufen, Aspirin, Cilostazol and Clopidogrel in the Treatment of Ischemic Stroke

Efficacy and Safety of Indobufen, Aspirin, Cilostazol, and Clopidogrel in the Treatment of Ischemic Stroke: a Single-center, Retrospective Study

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Ischemic Stroke
• Intervention / Treatment: Drug: indubufen, aspirin, clopidogrel, cilostazol

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 2000

Contacts and Locations

• Study Contact: Name: Jia Yin; Phone Number: 13802964883; Email: jiajiayin@139.com
• Study Contact Backup: Name: Jiayin Chen; Phone Number: 13337523808; Email: liuqiruismu@gmail.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Nanfang Hospital,Southern Medical University Recruiting

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

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.

Description

Inclusion Criteria:

1. Age ≥ 18 years;
2. Diagnosed with acute ischemic stroke (AIS) patients according to the Chinese Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke 2018 ;
3. Hospitalized in the Department of Neurology, Nanfang Hospital, Southern Medical University, between January 2020 and December 2025;
4. Received one of the following as a secondary prevention regimen within 7 days after discharge: indobufen, aspirin, clopidogrel, or cilostazol, either as monotherapy or as dual therapy;
5. Have follow-up records at 1 year after treatment initiation.

Exclusion Criteria:

1. Already having long-term anticoagulant therapy at baseline;
2. History of hemorrhagic stroke or active bleeding;
3. Severe hepatic or renal dysfunction (defined as AST/ALT > 3 times the upper limit of normal, or estimated glomerular filtration rate < 30 mL/min/1.73m²), end-stage disease, intracranial tumor, or intracranial infection.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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.	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

Collaborators and Investigators

• Sponsor: Nanfang Hospital, Southern Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: May 18, 2026
• First Submitted That Met QC Criteria: May 18, 2026
• First Posted (Actual): May 22, 2026

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 18, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Secondary prevention; Antiplatelet therapy; Stroke recurrence
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke; Ischemic Stroke; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Azoles; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Phenols; Benzene Derivatives; Quinolines; Thiophenes; Salicylates; Hydroxybenzoates; Tetrazoles; Ticlopidine; Thienopyridines; Clopidogrel; Cilostazol; Aspirin
• Other Study ID Numbers: NFEC-2026-179

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No