Table A1:

Study Design and Characteristics

Author, Year N (TAVI/SAVR) Enrollment Period	Study Design Statistical Analysis	Patient Population	Intervention	Comparator	Outcomes
Mack et al, 201918 1,000 (503/497) 2016–2017 PARTNER 3	Randomization using electronic system Multicentre Noninferiority trial (primary composite end point) Study results presented for as-treated (primary), intention-to-treat, and implanted populations Not blinded Case Review Committee reviewed all patient data before randomization Data Safety Monitoring Board independently examined all SAEs Clinical Events Committee adjudicated all primary and secondary end point events. Also adjudicated whether event was device- or procedure-related Independent core laboratories assessed all ECGs and CT angiograms	Severe calcific aortic valve stenosis ∘ AVA ≤ 1 cm2 or AVA index ≤ 0.6 cm2/m2 ∘ Jet velocity ≥ 4 m/s or mean gradient ≥ 40 mm Hg AND NYHA functional class ≥ 2 or exercise tolerance test demonstrates limited exercise capacity, abnormal blood pressure response, or arrhythmia) or asymptomatic with LVEF < 50% Heart team agrees that patient is at low risk and STS < 4% Exclusion Ineligible for transfemoral TAVI placement Severe aortic or mitral regurgitation Significant frailty Unicuspid, bicuspid, noncalcified aortic valve Preexisting mechanical or bioprosthetic heart valve in any position (except mitral ring) Anatomical features that increased risk of complications with either TAVI or SAVR	Balloon-expandable TAVI inserted via transfemoral route (Sapien 3 valve) Balloon aortic valvuloplasty before or after TAVI at investigator's discretion	SAVR (bioprosthetic valve)-sternotomy or minimally invasive/port access	Primary Outcome: Noninferiority Composite of all-cause mortality, stroke, or rehospitalizationa at 1 yb Secondary Outcomes Effectiveness Change in NYHA functional class at 30 d and 1 y Paravalvular and total aortic regurgitation at 30 d and 1 y Aortic valve stenosis at 30 d and 1 y Length of hospitalizationb Length of ICU stay Discharge location Days alive and out of hospital at 1 y Poor treatment outcomeb (composite of death or a low KCCQ overall summary score) at 30 db 6-min walk test at 30 d and 1 y Quality of life (change in EQ-5D-5L, SF-36, KCCQ scores) at 30 d and 1 y Structural valve deterioration at 1 y Safety Composite of death or strokeb Mortality (all-cause and cardiovascular) at 30 d and 1 y Stroke (disabling and nondisabling)c at 30 db and 1 y New-onset atrial fibrillation at 30 db and 1 y Major vascular complications at 30 d and 1 y Life-threatening/disabling or major bleeding complications at 30 d and 1 y Myocardial infarction at 30 d and 1 y Acute kidney injury at 30 d Requirement for renal replacement therapy at 1 y New pacemaker implantation for new or worsened conduction disturbances at 30 d and 1 y Coronary obstruction requiring intervention at 30 d and 1 y Rehospitalization (valve- or procedure-related, including heart failure) at 30 d and 1 y
Popma et al, 201917 1,468 (734/734) 2016–2018 Evolut LRT	Randomization using electronic system Stratified by need for coronary artery revascularization Multicentre Noninferiority trial (primary composite end point) Unblinded Screening committee confirmed patient eligibility Bayesian statistical methods with noninformative prior distributions were used Study results presented for the as-treated (primary), intention-to-treat, or implanted populations, and perprotocol population	Severe aortic valve stenosis Symptomatic patients: ∘ AVA ≤ 1 cm2 or AVA index ≤ 0.6 cm2/m2, or maximal aortic velocity ≥ 4 m/s or mean gradient ≥ 40 mm Hg Asymptomatic patients: ∘ Very severe aortic stenosis, AVA ≤ 1 cm2 or AVA index ≤ 0.6 cm2/m2 and maximal aortic velocity ≥ 5 m/s or mean gradient ≥ 60 mm Hg OR ∘ Aortic valve area of ≤ 1.0 cm2 (or aortic valve area index of ≤ 0.6 cm2/m2), AND a mean gradient ≥ 40 mm Hg or maximal aortic valve velocity ≥ 4.0 m/sec by transthoracic echocardiography at rest, AND an exercise tolerance test that demonstrates limited exercise capacity, abnormal blood pressure response, or arrhythmia OR ∘ Aortic valve area of ≤ 1.0 cm2 (or aortic valve area index of ≤ 0.6 cm2/m2), AND mean gradient ≥ 40 mm Hg, or maximal aortic valve velocity ≥ 4.0 m/sec by transthoracic ECG at rest, AND LVEF < 50% Low risk (STS < 3% as assessed by heart team) Exclusion Candidates for mechanical valves Severe aortic or mitral regurgitation Bicuspid aortic valve Preexisting mechanical or bioprosthetic heart valve in any position Moderate or severe mitral stenosis Prohibitive left ventricular outflow tract calcification	Self-expanding TAVI inserted via transfemoral route (CoreValve, Evolut R, Evolut PRO valve)	SAVR (bioprosthetic valve)	Primary Safety and Effectiveness Outcome: Noninferiority Composite of all-cause mortality or disabling stroke at 2 y Secondary Outcomes Effectiveness Transvalvular mean gradient at 1 y (noninferiority and superiority)b Effective orifice area at 1 y (noninferiority and superiority)b Change in NYHA functional class from baseline to 1 y (noninferiority)b Change in KCCQ score from baseline to 30 d (superiority) or 1 y (noninferiority)b Health-related quality of life (EQ-5D) at 1 y Valve-related dysfunction (moderate-severe prosthetic valve stenosis or moderate-severe prosthetic regurgitation) at 1 y Repeat hospitalization for aortic valve disease at 1 y Device success Hemodynamic performance Safety Composite of death, disabling stroke, life-threatening bleeding, major vascular complications, or stage 2 or 3 kidney injury at 30 d New pacemaker implantation at 30 d Prosthetic valve endocarditis at 1 y Prosthetic valve thrombosis at 1 y All stroke (disabling and nondisabling) at 1 y Life-threatening bleeding at 1 y Valve-related dysfunction requiring repeat procedure at 1 y

Abbreviations: AVA, aortic valve area; CT, computed tomography; ECG, electrocardiogram; EQ-5D, European Quality of Life in Five Dimensions; KCCQ, Kansas City Cardiomyopathy Questionnaire; ICU; intensive care unit; LVEF, left ventricular ejection fraction; NYHA, New York Heart Association; SAE, serious adverse event; SAVR, surgical aortic valve replacement; SF-36, Medical Outcomes Study 36-question Short-Form Health Survey; STS, Society of Thoracic Surgeons; TAVI, transcatheter aortic valve implantation.

^aAny hospitalization related to procedure, valve, or heart failure.

^bEnd points adjusted for multiple comparisons at 30-day timepoint.

^cAll patients underwent neurologic examinations at baseline and at 30 days. In case of suspected stroke after procedure, neurologic examinations including National Institutes of Health Stroke Scale assessment and modified Rankin scale at 90 days after event were performed.