Aspirin Versus Aspirin+Clopidogrel as Antithrombotic Treatment Following TAVI

Study Overview
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Brief Summary
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The purpose of this study is to compare aspirin/acetylsalicylic acid+ clopidogrel with aspirin/acetylsalicylic acid alone as antithrombotic treatment following TAVI for the prevention of major ischemic events (MI, ischemic stroke) or death without increasing the risk of major bleeding events.

Detailed Description
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Transcatheter aortic valve implantation (TAVI) has emerged as an alternative to standard aortic valve replacement for the treatment of patients considered to be at very high or prohibitive surgical risk. Nowadays the procedure is associated with a very high success rate (>95%) but major peri-procedural ischemic complications such as myocardial infarction (MI) or ischemic stroke occur in about 2% (0% to 17%) and 3% (2% to 7%) of the cases, respectively. The recently published PARTNER trial showed a stroke rate as high as 6.5% within the 30 days following TAVI, with most (77%) of these events diagnosed as major strokes. In order to avoid such ischemic complications full dose anticoagulation (usually intravenous heparin) is administered during the TAVI procedure, whereas aspirin (long-term) + clopidogrel (1 to 6 months) have been the recommended antithrombotic treatment following the procedure. However, this antithrombotic regime has been recommended on an empirical basis, and no studies have as yet shown the efficacy of aspirin + clopidogrel vs. aspirin alone or no antithrombotic treatment in preventing ischemic events following TAVI procedures. Also, patients undergoing TAVI nowadays are usually octogenarians and very frequently exhibit comorbidities such as hypertension, abnormal renal function or prior cerebrovascular disease, which significantly increase the risk of major bleeding. Indeed, TAVI procedures can also be associated with major vascular complications which in turn can complicate with life-threatening or major bleeding. It is well know that clopidogrel on top of aspirin is associated with a higher rate of major bleeding complications, especially in elderly patients. It would therefore be of major clinical relevance to determine the risk/benefit ratio of using a dual antithrombotic therapy following TAVI procedures in order to recommend the most appropriate antithrombotic treatment in this high-risk population. The ARTE trial is a multicenter randomized study to evaluate the efficacy and safety of aspirin/acetylsalicylic acid versus aspirin/acetylsalicylic acid+ clopidogrel as antithrombotic treatment after TAVI.

Official Title
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Aspirin Versus Aspirin + ClopidogRel as Antithrombotic Treatment Following Transcatheter Aortic Valve Implantation With the Edwards Valve. A Randomized Study (the ARTE Trial)

Conditions
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Aortic Valve Disease, Myocardial Infarction, Stroke, Bleeding

Intervention / Treatment
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* Drug: Clopidogrel
* Drug: Aspirin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients undergoing a TAVI procedure with the Edwards valve. Exclusion Criteria: Need for chronic anticoagulation treatment Major bleeding within the 3 months prior to the TAVI procedure Prior intracranial bleeding Drug-eluting stent implantation within the year prior to the TAVI procedure Allergy to clopidogrel and/or aspirin/acetylsalicylic acid

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 |
| --- | --- |
| Active Comparator: Aspirin +clopidogrel<br>Patients would be randomized within the month prior to the TAVI procedure to receive aspirin/acetylsalicylic acid (80-325 mg/d) + clopidogrel (75 mg/d) | Drug: Clopidogrel<br>* Clopidogrel therapy will start within 24 hrs before the TAVI procedure in cases where a transfemoral approach is used and within 24 hrs after the TAVI procedure in cases where a transapical approach is used. The initial dose of clopidogrel will be of 300 mg followed by 75 mg/die. The duration of clopidogrel treatment will be of 3 months.<br>* Other names: Plavix;Drug: Aspirin<br>* Aspirin/acetylsalicylic acid (80-325 mg/d). Aspirin/acetylsalicylic acid therapy will start at least 24 hrs before the TAVI procedure and continued for at least 6 months.<br>* Other names: Acetylsalicylic acid;|
| Active Comparator: Aspirin<br>Patients will be randomized within the month prior to the TAVI procedure to receive aspirin/acetylsalicylic acid (80-325 mg/d) | Drug: Aspirin<br>* Aspirin/acetylsalicylic acid (80-325 mg/d). Aspirin/acetylsalicylic acid therapy will start at least 24 hrs before the TAVI procedure and continued for at least 6 months.<br>* Other names: Acetylsalicylic acid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of death, MI, ischemic stroke/Transient ischemic attack (TIA) or life threatening/major bleeding at 3-month follow-up. | The composite endpoint of incidence of death, MI, ischemic stroke/Transient ischemic attack (TIA) or life life threatening/major bleeding at 3-month follow-up will be analyzed | 3-month follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of death, MI, ischemic stroke/TIA or life threatening/major bleeding at 30 days | The composite endpoint of Incidence of death, MI, ischemic stroke/TIA or life threatening/major bleeding at 30 days will be analyzed | 30 days | 
| Incidence of death, MI, ischemic stroke/TIA or life threatening/major bleeding at at 12-month follow-up | The composite endpoint of Incidence of death, MI, ischemic stroke/TIA or life threatening/major bleeding at at 12-month follow-up will be analyzed. | 12-month follow-up | 
| Incidence of MI or ischemic stroke at 30 days and at 12-month follow-up | The composite endpoint of incidence of MI or ischemic stroke at 30 days and at 12-month follow-up will be analyzed | 12-month follow-up | 
| Cardiovascular death at 30 days and at 12-month follow-up | The incidence of cardiovascular death at 30 days and at 12-month follow-up will be analyzed | 30 days and at 12-month follow-up | 
| Cost-effectiveness of clopidogrel on top of aspirin/acetylsalicylic acid following TAVI | Cost-effectiveness of clopidogrel on top of aspirin/acetylsalicylic acid following TAVI will be analyzed | 30 days and at 12-month follow-up | 
| Rate of minor bleeding at 30 days and at 12-month follow-up | Rate of minor bleeding at 30 days and at 12-month follow-up will be analyzed | 30 days and at 12-month follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Transcatheter aortic valve implantation, Antithrombotic treatment, Clopidogrel, Aspirin/acetylsalicylic acid, Myocardial Infarction, Ischemic stroke, Major bleeding