Effects of Intensive Antiplatelet Therapy for Patients With Clopidogrel Resistance After Coronary Stent Implantation

Study Overview
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Brief Summary
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Clopidogrel resistance (CR) or low-responsiveness is associated with increased risk of ischemic events and can be detected by laboratory tests. This multicenter, randomized study is aimed to explore the efficacy and safety of intensive antiplatelet therapy (i.e. double clopidogrel maintenance dose and/or additional cilostazol)for patients with CR after coronary stenting.

Conditions
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Acute Coronary Syndromes, Percutaneous Coronary Intervention, Clopidogrel Low Responsiveness

Intervention / Treatment
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* Drug: aspirin, clopidogrel
* Drug: aspirin, clopidogrel, cilostazol


Participation Criteria
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Eligibility Criteria
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Inclusion Criterial: aged 35 to 75 years acute coronary syndromes underwent successful coronary stent implantation informed consent Exclusion Criteria: contraindications to antiplatelet therapy history of intracranial bleeding known bleeding disorders severe liver or kidney disease pregnancy left main coronary artery disease planned non cardiac surgery within 1 year end stage of other serious disease with life expectancy less than 1 year heart failure with NYHA grade 3 to 4

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: standard group<br>patients in this group received standard dual antiplatelet therapy, i.e. aspirin 300mg/d and clopidogrel 75mg/d | Drug: aspirin, clopidogrel<br>* patients in the standard group received standard dual antiplatelet therapy: aspirin 300mg/d for 30 days followed by 100mg/d indefinitely, clopidogrel 75mg/d for at least 1 year<br>|
| Experimental: intensive group<br>patients in this group received intensive antiplatelet therapy and the regimen can be adjusted according to results of platelet aggregation function test by LTA | Drug: aspirin, clopidogrel, cilostazol<br>* Firstly,all patients in this group were received aspirin 300mg/d and clopidogrel 150mg/d for 3 days. Then a platelet aggregation function test was performed. The regimen will lasted for another 27 days if patients were judged as responsive to current clopidogrel dose. Patients still with clopidogrel resistance were then randomly assigned to receive clopidogrel 75mg/d plus cilostazol 100mg, twice per day or clopidogrel 150mg/d plus cilostazol 50mg, twice per day for 27 days. At 30-day, a repeat platelet aggregation function test wil performed for all patients. Then a standard dual antiplatelet regimen with aspirin 100mg/d indefinitely and clopidogrel 75mg/d for at least 1 year will be prescribed for all patients.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major ischemic cardiovascular events | defined as a composite of cardiac death, myocardial infarction or stroke | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stent thrombosis | according to ARC definition | 1 year | 
| major adverse cardiac and cerebral events(MACCE) | defined as a composite of cardiac death, myocardial infarction, target vessel revascularization or stroke | 1 year | 
| Hemorrhagic events | according to TIMI bleeding definition | within 1 year | 
| reduction in ADP induced platelet aggregation | assessed by LTA (Packs-4 Aggregometer, Helena labs, Beaumont, Texas) | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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antiplatelet therapy, clopidogrel low responsiveness, acute coronary syndromes, percutaneous coronary intervention, cilostazol