Aortic Valve Disease, Bleeding, Myocardial Infarction, Stroke
Conditions
Keywords
Transcatheter aortic valve implantation, Antithrombotic treatment, Clopidogrel, Aspirin/acetylsalicylic acid, Myocardial Infarction, Ischemic stroke, Major bleeding
Brief summary
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
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.
Interventions
DRUGClopidogrel
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.
DRUGAspirin
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.
Sponsors
Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Quebec
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of death, MI, ischemic stroke/Transient ischemic attack (TIA) or life threatening/major bleeding at 3-month follow-up. | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of death, MI, ischemic stroke/TIA or life threatening/major bleeding at at 12-month follow-up | 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. |
| Incidence of MI or ischemic stroke at 30 days and at 12-month follow-up | 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 |
| Incidence of death, MI, ischemic stroke/TIA or life threatening/major bleeding at 30 days | 30 days | The composite endpoint of Incidence of death, MI, ischemic stroke/TIA or life threatening/major bleeding at 30 days will be analyzed |
| Cost-effectiveness of clopidogrel on top of aspirin/acetylsalicylic acid following TAVI | 30 days and at 12-month follow-up | Cost-effectiveness of clopidogrel on top of aspirin/acetylsalicylic acid following TAVI will be analyzed |
| Rate of minor bleeding at 30 days and at 12-month follow-up | 30 days and at 12-month follow-up | Rate of minor bleeding at 30 days and at 12-month follow-up will be analyzed |
| Cardiovascular death at 30 days and at 12-month follow-up | 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 |
Countries
Canada, Chile, Spain
Outcome results
None listed