NCT02664649

Anti-Thrombotic Strategy After Trans-Aortic Valve Implantation for Aortic Stenosis

Anti-Thrombotic Strategy to Lower All Cardiovascular and Neurologic Ischemic and Hemorrhagic Events After Trans-Aortic Valve Implantation for Aortic Stenosis

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 1,510 (estimated)
• Sponsor: Assistance Publique - Hôpitaux de Paris · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

ATLANTIS is a multicenter, phase IIIb, prospective, open-label, randomized trial. The objective of this study is to demonstrate superiority of a strategy of anticoagulation with apixaban (Anti-Xa Group) as compared to the current standard of care in patients who have undergone a successful TAVI procedure. The randomization is stratified according to the presence or not of a mandatory indication for anticoagulation for a reason other than the TAVI procedure (e.g. atrial fibrillation or DVT/PE).

Detailed description

Guidelines on antithrombotic therapy after TAVI are scarce and no randomized evaluation has been performed to demonstrate what the optimal antithrombotic strategy is. The rates of major stroke and of major bleeding on DAPT, the standard of care in TAVI (Class IIb LOE C), are respectively as high as 3% and 10% within the first 30 days excluding the perioperative period. In addition, the rate of MACCE is estimated to be of 15% on DAPT. However, more than half of senior patients display high on-clopidogrel platelet reactivity, less than 1/3 undergo coronary stent implantation prior to valve replacement and more than 1/3 display transient atrial fibrillation (AF) during hospital stay. Anticoagulation appears therefore to be underused in this high stroke risk population and has never been evaluated in post-TAVI procedures. Non-vitamin K Oral Anticoagulants (NOAC) have shown superiority or non-inferiority versus VKA to prevent cardio-embolic events with a consistent reduction in intracranial bleeds in patients with non-valvular AF. Apixaban, a direct anti-Xa inhibitor, is the only NOAC which has demonstrated a mortality benefit associated with significant reductions in embolism and major bleeding versus VKA. In addition, apixaban is the only NOAC which has demonstrated superiority over aspirin to prevent cardio-embolic events with a similar safety profile in non-valvular AF patients with a contraindication to VKA. The investigators therefore formulate the hypothesis that apixaban is superior to SOC to prevent cardiovascular events in post-TAVI procedures. The main purpose is to demonstrate superiority of a strategy of anticoagulation with apixaban 5mg bid (Anti-Xa Group) with dose adjustment as compared to the current standard of care (SOC Group = VKA or Antiplatelet therapy) as measured by the time from randomization to the first occurrence of any event of the composite endpoint of death, myocardial infarction, stroke/TIA/systemic embolism, intracardiac or bioprosthesis thrombus, episode of deep vein thrombosis or pulmonary embolism, life-threatening or disabling or major bleeding at one year follow-up defined according to VARC2. Patients who underwent a clinically successful TAVI procedure. Non-inclusion criteria include any recent acute cardiovascular event, mechanical heart valve, necessary use of prasugrel or ticagrelor (new P2Y12 inhibitors), concomitant medical illness associated with reduced survival, end stage renal failure defined as a creatinine clearance \< 15mL/min.

Conditions

• Symptomatic Aortic Stenosis
• Eligible for Transcatheter Aortic Valve Replacement

Interventions

Type	Name	Description
DRUG	Apixaban	Investigational Product is open label apixaban 5 mg tablets taken orally two times a day for 12 months. Subjects with 2 or more of the following characteristics will take apixaban 2.5 mg tablets orally twice daily: age ≥80 years, body weight \<60 kg, serum creatinine ≥1.5 mg/dL \[133 μMol/L\]. \- Also, subjects with severe renal insufficiency \[calculated Creatinine Clearance (Cr.Cl.) (Cockroft-Gault) between 15-29 ml/min\] will take apixaban 2.5 mg tablets orally twice daily
DRUG	Standard of care	VKA or Antiplatelet therapy

Timeline

• Start date: 2016-08-26
• Primary completion: 2020-10-15
• Completion: 2020-10-15
• First posted: 2016-01-27
• Last updated: 2021-02-25

Locations

4 sites across 4 countries: France, Germany, Italy, Spain