Dual Antiplatelet Therapy in Patients With Aspirin Resistance Following Coronary Artery Bypass Grafting

Study Overview
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Brief Summary
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Reactive platelet hyperactivity following coronary artery bypass grafting (CABG) might lead to thrombotic complications and major ischemic cardiac events. The aim of this study is to evaluate the changes in platelet reactivity following CABG and to clarify a potentially beneficial effect of dual antiplatelet therapy in the group of patients with documented aspirin resistance following CABG. Platelet function will be assessed by multiple electrode aggregometry. Aortocoronary vein graft disease is comprised of three distinct but interrelated pathological processes: thrombosis, intimal hyperplasia and atherosclerosis. Early vein thrombosis is a major cause of vein graft attrition during the first month after CABG. Bypass patency can be improved with antiplatelet therapy which is the mainstay of treatment for patients after CABG. A beneficial effect of acetylsalicylic acid (ASA) on vein graft patency has been previously shown. Some patients experience thrombotic events despite continuous aspirin administration after CABG. The investigators hypothesized that low responsiveness to aspirin might be a precipitating factor for adverse thrombotic events following CABG. Low responsiveness to ASA, as assessed by platelet function tests, varies widely among patients. The etiology of postoperative platelet hyperactivity remains to be elucidated. In this study a new point-of-care assay named multiple electrode aggregometry (MEA) using a device called Multiplate analyzer (Dynabyte, Munich, Germany) has been utilized. It allows for rapid and standardized assessment of platelet function parameters. This is a prospective randomized trial. The aim of the study is to document whether introduction of dual antiplatelet therapy in patients with ASA resistance will lead to a lower incidence of major adverse cardiac events (MACE) at a six month follow up. The composite endpoint will include death, non-fatal myocardial infarction, stroke and cardiac rehospitalization. All patients will receive 300 mg of ASA starting 6 hours after surgery, provided that the chest tube output is minimal. On postoperative day 4 their platelet function will be assessed using the above mentioned MEA. The patients found to be aspirin resistant will then undergo the process of randomization. The first arm will include patients with ASA resistance in whom no additional antiaggregation will be administered. In the second arm the investigators will include patients who were randomized to receive 75 mg of clopidogrel in addition to the standard antiplatelet regimen of 300 mg of ASA. Platelet function monitoring allows for individual tailoring of the antiplatelet therapy. The goal of this study is to define whether this strategy will lead to improved patient outcomes. Both major and minor bleeding complications will be strictly monitored and reported.

Official Title
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Dual Antiplatelet Therapy in Patients With Aspirin Resistance Following Coronary Artery Bypass Grafting

Conditions
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Coronary Artery Disease, Aspirin Resistance

Intervention / Treatment
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* Drug: Clopidogrel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Isolated coronary artery bypass grafting Patients older than 18 years Written informed consent Accurate antiplatelet therapy administration documentation Exclusion Criteria: Missing consent Patients with cardiac surgical procedures other than isolated CABG Antiplatelet therapy other than aspirin 300 mg after CABG Previous PCI requiring clopidogrel therapy after CABG Patients with unknown preoperative anti-platelet status Urgent or emergent surgery Off-pump CABG Re-Do CABG Patients younger than 18 years

Ages Eligible for Study
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Minimum Age: 18 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: aspirin low responders monotherapy<br>patients with inappropriate response to aspirin assessed by multiple electrode aggregometry | |
| Active Comparator: aspirin low responders dual antiplatelet therapy<br>patients with inappropriate response to aspirin 300 mg therapy after CABG, randomized to receive clopidogrel 75 mg in addition to aspirin | Drug: Clopidogrel<br>* patients with inappropriate response to aspirin 300 mg after CABG, assessed by multiple electrode aggregometry are randomized to receive clopidogrel 75 mg daily dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MACE events | MACE: death; non-fatal myocardial infarction; stroke; cardiac rehospitalization | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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aspirin resistance, coronary artery bypass grafting, multiple electrode aggregometry, multiplate