Apixaban for the Prevention of Latent Biological Valve Thrombosis

Clinical Hospital Centre Zagreb

Status and phase: Enrolling; Phase 4

Conditions: Aortic Valve Replacement; Antithrombotic Therapy; Bioprosthetic Valve Thrombosis; Rapid Deployment Valves

Treatments: Diagnostic Test: Echocardiography; Procedure: Aortic valve replacement surgery; Diagnostic Test: Computed tomography

Study type: Interventional

Funder types: Other

Identifiers

NCT06184113

8.1-23/77-3 02/013 AG;

Details and patient eligibility

About

Background: The optimal antithrombotic strategy early after aortic valve replacement surgery with a biological valve remains controversial due to lack of high-quality evidence. Either oral anticoagulants or acetylsalicylic acid should be considered for the first three months. Hypo-attenuated leaflet thickening on cardiac compute tomography has been associated with latent bioprosthetic valve thrombosis and may be prevented with anticoagulation. The investigators hypothesize that anticoagulation with apixaban is superior to single antiplatelet therapy with acetylsalicylic acid in reduction of hypo-attenuated leaflet thickening of bioprosthetic valves after aortic valve replacement.

Methods: In this prospective, open-label, randomized trial patients without an indication for oral anticoagulation undergoing isolated aortic valve replacement surgery with novel rapid-deployment bioprosthetic valves will be randomized. The treatment group will receive 5 mg of apixaban twice a day for the first three months and 100 mg of acetylsalicylic acid thereafter. The control group will have 100 mg of acetylsalicylic acid once a day indefinitely. After the three-month treatment period a contrast enhanced electrocardiogram-gated cardiac computed tomography will be performed to identify hypo-attenuated leaflet thickening of the bioprosthetic valve. The primary objective of the study is to assess possible superiority of the treatment group in the prevention of hypo-attenuated leaflet thickening three months after randomization. Secondary objective is to assess possible noninferiority for safety of apixaban-based strategy when compared to acetylsalicylic acid at three months.

Discussion: Antithrombotic therapy after aortic valve replacement surgery is used to prevent valve thrombosis and systemic thromboembolism. Latent bioprosthetic valve thrombosis is a precursor of clinically significant prosthetic valve dysfunction or thromboembolic event. The hallmark feature of latent bioprosthetic valve thrombosis is hypo-attenuated leaflet thickening on cardiac computed tomography. Subclinical leaflet thrombosis occurs frequently in bioprosthetic aortic valves, more commonly in transcatheter than in surgical valves. There is no evidence on the effect of direct oral anticoagulants on the incidence of hypo-attenuated leaflet thickening after surgical aortic valve replacement with rapid deployment bioprostheses.

Enrollment: 166 estimated patients

Sex: All

Ages: 65+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

• Men and women aged 65 or older with aortic valve stenosis undergoing successful isolated first-time aortic valve replacement with a rapid deployment bioprosthetic valve
• Signed informed consent to participate in the research

Exclusion Criteria:

• Indication for long-term use of anticoagulant therapy
• Indication for dual antiplatelet therapy
• Contraindication to anticoagulation or antiplatelet therapy
• Inability to start the study drug within the planned randomization period
• History of atrial fibrillation
• Known hemorrhagic diathesis
• Presence of other significant heart pathology
• Prior open-heart surgery
• Presence of liver failure or other coagulopathy
• Aortic valve infective endocarditis
• Severe renal failure
• Allergy to iodine contrast

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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166 participants in 2 patient groups

Intervention Arm

Experimental group

Description:

Patients randomised to the intervention arm will receive an open-label dose adjusted apixaban twice a day. The treatment will be continued for three months. After the tree-month treatment period apixaban will be stopped and acetylsalicylic acid will be started.

Treatment:

Diagnostic Test: Computed tomography

Diagnostic Test: Echocardiography

Procedure: Aortic valve replacement surgery

Control Arm

Active Comparator group

Description:

Patients assigned to the control arm will receive an open-label low dose acetylsalicylic acid indefinitely.

Treatment:

Diagnostic Test: Computed tomography

Diagnostic Test: Echocardiography

Procedure: Aortic valve replacement surgery