Strategies to Prevent Transcatheter Heart Valve Dysfunction in Low Risk Transcatheter Aortic Valve Replacement

This study aims to examine the optimal anticoagulation/antiplatelet regimen in low risk
patients undergoing TAVR. The prospective randomized controlled arm of this study will assess
the utility of short-term oral anticoagulation with warfarin compared to antiplatelet therapy
alone after TAVR in low risk patients to reduce the incidence of structural valve
deterioration manifest as clinical events, increased aortic valve gradients or transvalvular
regurgitation, or subclinical leaflet thrombosis. Low risk subjects with symptomatic severe
aortic stenosis will be enrolled to undergo TAVR. Following TAVR, subjects will be randomized
to receive warfarin plus low dose Aspirin or low dose Aspirin monotherapy for 30-45 days.
Subjects with other indications for anticoagulation (e.g. AF, DVT or PE) will not be
randomized and instead will be followed in a separate registry arm. Baseline demographic,
clinical, non-invasive imaging (echocardiography and CT), TAVR procedural details, clinical
follow up data will be prospectively collected for all subjects. Echocardiography and
contrast-enhanced 4D cardiac CT will be performed in all subjects between 30-45 days after
TAVR to evaluate for evidence of structural valve deterioration.

This multicenter prospective randomized study will enroll 200 consecutive low risk subjects
with symptomatic severe aortic stenosis into the treatment arms of the study. Up to 100
additional subjects with a pre-existing indication for anticoagulation (e.g. atrial
fibrillation, deep venous thrombosis or pulmonary embolism) or who are not eligible for
randomization after TAVR due to development of a new indication for anticoagulation will be
enrolled into the registry arm of the study.

Inclusion of this registry arm will ensure that the secondary objective pooled analysis of
patient level data from this study and the Low Risk TAVR (LRT) study, truly represents an
all-comers cohort of low risk patients undergoing TAVR, and does not exclude a significant
subgroup.

Inclusion Criteria:

- Severe, degenerative AS, defined as:

- Mean aortic valve gradient ≥40 mm Hg OR Vmax ≥4 m/sec AND

- Calculated aortic valve area ≤1.0 cm2 OR aortic valve area index ≤0.6 cm2/m2

- Symptomatic AS, defined as a history of at least one of the following:

- Dyspnea that qualifies at New York Heart Association (NYHA) class II or greater

- Angina pectoris

- Cardiac syncope

- The Heart Team agrees that the patient is low-risk, quantified by an estimated risk of
death ≤3% by the calculated STS score for operative mortality at 30 days; AND agrees
that SAVR would be an appropriate therapy if offered

- A surgeon who is experienced in Surgical Aortic Valve Replacement (SAVR) has spoken
with the patient in person and stipulates that the patient understands his/her
alternatives for FDA approved therapy, including open heart surgery to replace their
aortic valve

- The institutional Heart Team determines that transfemoral TAVR is appropriate

- Aortic valve anatomy and dimensions suitable for TAVR using a commercially available
valve

- Iliofemoral artery anatomy and dimensions suitable for transfemoral TAVR using a
commercially available valve and delivery system

- Procedure status is elective

- Expected survival is at least 24 months

Exclusion Criteria:

- Subject unable or unwilling to give informed consent

- Concomitant disease of another heart valve or the aorta that requires either
transcatheter or surgical intervention

- Any condition that is considered a contraindication for placement of a bioprosthetic
aortic valve (e.g. patient requires a mechanical aortic valve)

- Aortic stenosis secondary to a bicuspid aortic valve

- Prior bioprosthetic surgical aortic valve replacement

- Mechanical heart valve in another position

- End-stage renal disease requiring hemodialysis or peritoneal dialysis, or a creatinine
clearance <20 cc/min

- Left ventricular ejection fraction <20%

- Recent (<6 months) history of stroke

- Symptomatic carotid or vertebral artery disease, or recent (<6 weeks) surgical or
endovascular treatment of carotid stenosis

- Any contraindication to oral antiplatelet or anticoagulation therapy following the
procedure, including recent or ongoing bleeding, or HASBLED score >3 (Table 2 -
HASBLED scoring system)

- Severe coronary artery disease that is unrevascularized

- Recent (<30 days) acute myocardial infarction

- Patient cannot undergo transfemoral TAVR for anatomic reasons (as determined by
supplemental imaging studies); this would include inadequate size of iliofemoral
access vessels or an aortic annulus size that is not accommodated by the commercially
available valves

- Any comorbidity not captured by the STS score that would make SAVR high risk, as
determined by a cardiothoracic surgeon who is a member of the heart team; this
includes:

- Porcelain or severely atherosclerotic aorta

- Frailty

- Hostile chest

- Internal mammary artery or other conduit either crosses midline of sternum or is
adherent to sternum

- Severe pulmonary hypertension (PA systolic pressure > 2/3 of systemic pressure)

- Severe right ventricular dysfunction

- Ongoing sepsis or infective endocarditis

- Severe chronic obstructive pulmonary disease, as demonstrated by forced expiratory
volume (FEV1) <750 cc

- Liver failure with Childs class C or D

- Pre-procedure shock, inotropes, mechanical assist device, or cardiac arrest

- Pregnancy or intent to become pregnant prior to completion of all protocol follow-up
procedures

- Known allergy to warfarin or aspirin