Aspirin Versus Aspirin+Clopidogrel as Antithrombotic Treatment Following TAVI "ARTE"

Active, not recruiting

Phase 4 Results N/A

Trial Description

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.

Conditions

Interventions

  • Clopidogrel (Plavix┬«)Drug
    Other Names: Plavix
    Intervention Desc: 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.
    ARM 1: Kind: Experimental
    Label: Aspirin +clopidogrel
    Description: 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)
  • Aspirin Drug
    Other Names: clopidogrel; combination aspirin-dipyridamole
    Intervention Desc: 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.
    ARM 1: Kind: Experimental
    Label: Aspirin +clopidogrel
    Description: 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)
    ARM 2: Kind: Experimental
    Label: Aspirin
    Description: Patients will be randomized within the month prior to the TAVI procedure to receive aspirin/acetylsalicylic acid (80-325 mg/d)
  • Aspirin/acetylsalicylic acid +clopidogrel Drug
    Intervention Desc: Aspirin/acetylsalicylic acid (80-325 mg/d) + clopidogrel (75 mg/d). Aspirin/acetylsalicylic acid therapy will start at least 24 hrs before the TAVI procedure and continued for at least 6 months. 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.
    ARM 1: Kind: Experimental
    Label: Aspirin/acetylsalicylic acid +clopidogrel
    Description: 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)
  • Aspirin/acetylsalicylic acid Drug
    Intervention Desc: 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.
    ARM 1: Kind: Experimental
    Label: Aspirin/acetylsalicylic acid
    Description: Patients will be randomized within the month prior to the TAVI procedure to receive aspirin/acetylsalicylic acid (80-325 mg/d)

Trial Design

  • Allocation: Randomized
  • Masking: Open Label
  • Purpose: Prevention
  • Endpoint: Safety/Efficacy Study
  • Intervention: Parallel Assignment

Outcomes

Type Measure Time Frame Safety Issue
Primary Incidence of death, MI, ischemic stroke/Transient ischemic attack (TIA) or life threatening/major bleeding at 3-month follow-up. 3-month follow-up Yes
Secondary Incidence of death, MI, ischemic stroke/TIA or life threatening/major bleeding at 30 days 30 days Yes
Secondary Incidence of death, MI, ischemic stroke/TIA or life threatening/major bleeding at at 12-month follow-up 12-month follow-up Yes
Secondary Incidence of MI or ischemic stroke at 30 days and at 12-month follow-up 12-month follow-up Yes
Secondary Cardiovascular death at 30 days and at 12-month follow-up 30 days and at 12-month follow-up Yes
Secondary Cost-effectiveness of clopidogrel on top of aspirin/acetylsalicylic acid following TAVI 30 days and at 12-month follow-up Yes
Secondary Rate of minor bleeding at 30 days and at 12-month follow-up 30 days and at 12-month follow-up Yes

Sponsors