Transcatheter or Surgical Aortic Valve Replacement in Intermediate Risk Patients with Aortic Stenosis Description: The goal of the trial was to assess the safety and efficacy of balloon-expandable transcatheter aortic valve replacement (TAVR) compared with surgical aortic valve replacement (SAVR) in intermediate-risk patients. Contribution: The PARTNER 2A trial showed that TAVR is noninferior to SAVR for the primary endpoint at 2 years for the treatment of severe aortic stenosis in intermediate-risk patients (STS PROM 4-8%; median 5.8%).

Study Design Patients were stratified in cohorts according to access route (transfemoral [76.3%] or transthoracic) and were then randomly assigned (in a 1:1 ratio) to undergo either TAVR (n = 1,011) or SAVR (n = 1,021). TAVR was performed with the balloon-expandable TAVR Sapien XT valve system. Total number of enrollees: 2,032 Duration of follow-up: 2 years Mean patient age: 81.6 years Percentage female: 46%

Other salient features/characteristics: Median Society of Thoracic Surgeons (STS) PROM score: 5.8% (>5% had an STS PROM of >10%) Coronary artery disease: 68%, cardiovascular disease: 32%, peripheral artery disease: 30% Oxygen-dependent chronic obstructive pulmonary disease: 3.3% 5 m walk distance >7 seconds (measure of frailty): 45% Left ventricular ejection fraction: 56%

Inclusion criteria: Severe symptomatic aortic stenosis STS PROM ≥4%. Patients with an STS risk score of <4.0% could also be enrolled if there were coexisting conditions that were not represented in the risk model Heart team (including examining cardiac surgeon) agrees on eligibility including assessment that TAVR or SAVR is appropriate Study patient agrees to undergo SAVR – if randomized to control treatment

Principal Findings: Primary endpoint: All-cause mortality or disabling stroke for TAVR vs. SAVR at 2 years: 19.3% vs. 21.1%, p = 0.001 for noninferiority, p = 0.33 for superiority Also at 2 years (TAVR vs. SAVR): All-cause mortality: 16.7% vs. 18.0%, p = 0.45 Cardiovascular mortality: 10.1% vs. 11.3%, p = 0.38 Disabling stroke: 6.2% vs. 6.4%, p = 0.83

Secondary outcomes for TAVR vs. SAVR: Intraprocedural valve embolization: 0.1% vs. 0% Intensive care unit length of stay: 2 vs. 4 days, p < 0.001 Index length of stay: 6 vs. 9 days, p < 0.001 All-cause mortality at 30 days: 3.9% vs. 4.1%, p = 0.78 Any neurological event at 30 days: 6.4% vs. 6.5%, p = 0.94; all strokes at 30 days: 5.5% vs. 6.1%, p = 0.57 Major vascular complication at 30 days: 7.9% vs. 5.0%, p = 0.008 Life-threatening or disabling bleeding at 30 days: 10.4% vs. 43.4%, p < 0.0001 New atrial fibrillation at 30 days: 9.1% vs. 26.4%, p < 0.001 New permanent pacemaker at 30 days: 8.5% vs. 6.9%, p = 0.17 Rehospitalization at 2 years: 19.6% vs. 17.3%, p = 0.22 Aortic valve area at 2 years: 1.54 cm2 vs. 1.4 cm2, p < 0.001 Moderate to severe paravalvular aortic regurgitation (leak) (PVL) at 2 years:  8.0% vs. 0.6%, p < 0.001

Transfemoral access cohort: All-cause mortality or disabling stroke at 2 years for TAVR vs. SAVR: 16.8% vs. 20.4%, hazard ratio 0.79, 95% confidence interval 0.62-1.00, p = 0.05

Interpretation: The results of this trial indicate that TAVR is noninferior to SAVR for the primary endpoint of mortality/disabling stroke at 2 years for the treatment of severe symptomatic aortic stenosis in intermediate-risk patients (STS PROM score 4-8%; median 5.8%). Transfemoral TAVR was possible in about 75% of the patients, and in these patients, TAVR appeared to be superior to SAVR. Vascular complications were higher in TAVR patients at 30 days, while new-onset atrial fibrillation, acute kidney injury, and bleeding were higher in the SAVR arm. Valve performance at 2 years was similar between the two strategies, although moderate to severe PVL was significantly higher in the TAVR arm at 2 years.