Aspirin Monotherapy Versus Sequential Warfarin-Aspirin Therapy After TAVR in Patients With Pure Aortic Regurgitation

Shanghai Zhongshan Hospital1,172 enrolled

Overview

This multicenter randomized controlled trial evaluates antithrombotic strategies post-TAVR in severe aortic regurgitation patients without long-term anticoagulation. Patients are randomized 1:1 to aspirin 75-100 mg daily for 12 months versus warfarin (INR 2-3) for 6 months followed by aspirin for 6 months. Primary hypothesis: aspirin is superior for bleeding and non-inferior for death/thrombosis. Primary endpoint is a composite of death, stroke, thrombosis, MI, embolism, and major bleeding at 1 year. Sample size: 1172. Follow-up: 30 days, 6 months, 12 months.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

1,172

Conditions

Aortic Regurgitation Disease

Interventions

Aspirin

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Age ≥18 years. * Patients with severe aortic regurgitation (AR) who achieve technical success after TAVR using devices specifically indicated for AR (per VARC-3 criteria). * Trileaflet aortic valve anatomy. * No long-term anticoagulation indication (including but not limited to: atrial fibrillation, mechanical mitral valve prosthesis, deep vein thrombosis, pulmonary embolism, left ventricular thrombus, pulmonary hypertension, or coagulation disorders) as confirmed by the investigator. * Signed written informed consent and willingness to comply with randomization, study procedures, and follow-up. Exclusion Criteria: * Need for oral anticoagulation or dual antiplatelet therapy, or need for oral or intravenous strong CYP3A inhibitors that cannot be paused during the study period. * Active pathological bleeding, subdural hematoma, or history of intracranial hemorrhage. * Ischemic stroke within 30 days before TAVR. * Acute myocardial infarction within 30 days. * Severe hepatic insufficiency (cirrhosis, hepatic decompensation). * Severe renal insufficiency (eGFR \< 30 mL/min/1.73 m²) or need for renal replacement therapy. * Stent implantation (including coronary, carotid, or peripheral arteries) within 12 months before TAVR, or planned stent implantation within 1 year after TAVR. * Coronary artery bypass grafting (CABG) within 12 months before TAVR. * Allergy, intolerance, or known resistance to aspirin, clopidogrel, or warfarin. * Known coagulation disorders or bleeding diathesis (including but not limited to platelet count ≤50,000/mm³ at screening). * Any contraindication to anticoagulation therapy. * Prior aortic valve prosthesis (mechanical or bioprosthetic); mitral valve bioprosthesis replacement within 1 year before TAVR; or prior mitral mechanical valve replacement; or prior tricuspid valve replacement. * Emergency TAVR with cardiogenic shock manifesting as low cardiac output, vasopressor or respiratory dependence, or mechanical hemodynamic support. * Life expectancy \<1 year (e.g., terminal malignancy). * Participation in another investigational drug or device clinical study (patients who have completed the primary endpoint of the study and are currently in long-term follow-up are not excluded). * Pregnancy or planned pregnancy, or use of estrogen or estrogen-like drugs (for women with suspected pregnancy, serum or urine human chorionic gonadotropin test must be negative before enrollment). * Any other condition deemed by the investigator to be inappropriate for study participation.

Outcomes

Primary Outcomes

Number of Participants Who Experienced Non-hierarchical Composite Endpoint

The primary endpoint is a non-hierarchical composite endpoint including all-cause death, stroke, prosthetic valve thrombosis, intracardiac thrombosis, myocardial infarction, deep vein thrombosis or pulmonary embolism, systemic embolism, and life-threatening, disabling, or major bleeding (VARC-3 definition).

Time frame: 12 months post-procedure

Secondary Outcomes

Number of Participants Who Experienced Composite Endpoint of All-Cause Death, Ischemic Stroke, Valve/Intracardiac Thrombosis, and Myocardial Infarction.

The first key secondary endpoint is composite of all-cause death, ischemic stroke, valve/intracardiac thrombosis, and myocardial infarction.

Time frame: 12 months post-procedure

Number of Participants Who Experienced Composite of Life-threatening, Disabling, or Major Bleeding (based on VARC-3 criteria Type 2-4)

Life-threatening or disabling bleeding Fatal bleeding OR Bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, or pericardial necessitating pericardiocentesis, or intramuscular with compartment syndrome OR Bleeding causing hypovolemic shock or severe hypotension requiring vasopressors or surgery OR Overt source of bleeding with drop in haemoglobin of ≥5 g/dL or whole blood or packed red blood cells (RBCs) transfusion ≥4 unitsa Major bleeding Overt bleeding either associated with a drop in the haemoglobin level of at least 3.0 g/dL or requiring transfusion of two or three units of whole blood/RBC AND Does not meet criteria of life-threatening or disabling bleeding

Time frame: 12 months post-procedure

Number of Participants Who Experience Composite of Cardiovascular Death, Major Bleeding, Stroke, and Myocardial Infarction

Time frame: 12 months post-procedure

Number of Participants Who Experience Clinical Efficacy Composite Endpoint

Composite endpoint requiring all of the following: freedom from all-cause death; freedom from all stroke; no hospitalization for valve-related or procedure-related reasons; and KCCQ overall score ≥45 with no more than a 10-point decrease from baseline.

Time frame: 12 months post-procedure

Number of Participants Who Experienced All-Cause Death

Time frame: 12 months post-procedure

Number of Participants Who Experience Clinically Significant Prosthetic Valve Thrombosis (VARC-3)

Based on VARC-3 criteria, clinically significant prosthetic valve thrombosis defined as clinical. sequelae of a thromboembolic event (e.g. stroke, TIA, retinal occlusion, other evidence of systemic thromboembolism) or worsening valve stenosis/ regurgitation (e.g. signs of heart failure, syncope) and Haemodynamic valve deterioration Stage 2 or 3 or Confirmatory imaging (CT evidence of HALT or TEE findings) In the absence of clinical sequelae, both Haemodynamic valve deterioration Stage 3 and Confirmatory imaging (CT evidence of HALT or TEE findings)

Time frame: At 6 months and 12 months post-procedure

Number of Participants Who Experience Bioprosthetic Valve Deterioration Stage 3 by Echocardiography (VARC-3)

Bioprosthetic Valve Failure Stage 3 defined as increase in mean transvalvular gradient ≥20 mmHg resulting in mean gradient ≥30 mmHg with concomitant decrease in EOA ≥0.6 cm2 or ≥50% and/or decrease in Doppler velocity index ≥0.2 or ≥40% compared with echocardiographic assessment performed 1-3 months post-procedure, OR new occurrence, or increase of ≥2grades, of intraprosthetic AR resulting in severe AR

Time frame: 12 months post-procedure

Number of Participants Who Experience Hypo-Attenuated Leaflet Thickening (HALT) by CT

Time frame: 12 months post-procedure

Number of Participants Who Experienced Non-Procedure-Related Life-Threatening or Disabling Bleeding (VARC-3)

Time frame: At 30 days and 12 months post-procedure

Number of Participants Who Experienced Major Bleeding

Based on VARC 2 criteria

Time frame: At 30 days and 12 months post-procedure

Number of Participants Who Experienced Minor Bleeding

Based on VARC 2 criteria

Time frame: At 30 days and 12 months post-procedure

Number of Participants Who Experienced Aortic Valve Re-Intervention

Time frame: 12 months post-procedure

Number of Participants Who Experienced Heart Failure Re-Hospitalization

Time frame: 12 months post-procedure

Number of Participants Who Experienced Infective Endocarditis

Infective Endocarditis defined as: Meeting at least one of the following criteria: Fulfills the Duke criteria for endocarditis; Intraoperative evidence of an abscess, pus, or vegetation secondary to infection, confirmed by histology or microbiology; Autopsy evidence of an abscess, pus, or vegetation.

Time frame: 12 months post-procedure

Number of Participants Who Experienced Major Adverse Cardiovascular and Cerebrovascular Events (MACCE)

MACCE including cardiac death, aortic valve reintervention, stroke, myocardial infarction, heart failure readmission and life-threatening, disabling, or major bleeding.

Time frame: At 30 days and 12 months post-procedure

Number of Participants Who Experienced NYHA Class Improvement

Time frame: At 30 days and 12 months post-procedure

Aspirin Monotherapy Versus Sequential Warfarin-Aspirin Therapy After TAVR in Patients With Pure Aortic Regurgitation

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts