Placement of Aortic Transcatheter Valves 3 - PARTNER 3
Anthony A. Bavry

Contribution To Literature

The PARTNER 3 trial showed that in low-risk patients, TAVR was superior to SAVR at reducing death, stroke, or rehospitalization at 1 year.

Description

The goal of the trial was to evaluate transcatheter aortic valve replacement (TAVR) compared with surgical aortic valve replacement (SAVR) among low-risk patients with symptomatic severe aortic stenosis.

Study Design

- Randomized

- Parallel

Low-risk patients undergoing AVR were randomized to TAVR using the SAPIEN 3 valve (n = 503) versus SAVR (n = 497). The TAVR group received aspirin and clopidogrel 300 mg prior to the procedure and dual antiplatelet therapy for ≥1 month after the procedure.

- Total number of enrollees: 1,000

- Duration of follow-up: 1 year

- Mean patient age: 73 years

- Percentage female: 30%

- Percentage with diabetes: 31%

Inclusion criteria

- Symptomatic high-gradient aortic stenosis

- Suitable for transfemoral access

- Society of Thoracic Surgeons (STS) risk of 30-day mortality: <4.0%

Exclusion criteria

- Frailty

- Bicuspid aortic valve

- Anatomical features that increased the risk of complications

- Left ventricular ejection fraction <30%

- Myocardial infarction within the last month

- Stroke or transient ischemic attack within the last 90 days

- Severe aortic or mitral regurgitation

- Moderate mitral stenosis

- Pre-existing mechanical or bioprosthetic valve in any position

- Complex coronary artery disease including unprotected left main disease

- Symptomatic carotid or vertebral artery disease

- Anemia/thrombocytopenia or high risk for bleeding

- Severe lung disease or severe pulmonary artery hypertension

- Body mass index >50 kg/m2

Other salient features/characteristics

- STS risk of 30-day mortality: 1.9%

- Conscious sedation: 65%

Principal Findings

The primary outcome, all-cause mortality, stroke, or rehospitalization (related to the procedure, valve, or heart failure) at 1 year, occurred in 8.5% of the TAVR group compared with 15.1% of the SAVR group (p < 0.001 for noninferiority, p = 0.001 for superiority). Findings were the same in all prespecified subgroups.

Secondary outcomes

- Stroke at 30 days: 0.6% for TAVR vs. 2.4% for SAVR (p = 0.02)

- New-onset atrial fibrillation at 30 days: 5.0% for TAVR vs. 39.5% for SAVR (p < 0.001)

- Death or low Kansas City Cardiomyopathy Questionnaire – overall summary score (KCCQ-OS) at 30 days: 3.9% for TAVR vs. 30.6% for SAVR (p < 0.001)

- Death or disabling stroke at 1 year: 1.0% for TAVR vs. 2.9% for SAVR (p < 0.05)

- Mild paravalvular aortic regurgitation at 1 year: 29.4% for TAVR vs. 2.1% for SAVR (p < 0.05)

- Moderate to severe paravalvular aortic regurgitation at 1 year: 0.6% for TAVR vs. 0.5% for SAVR (p = not significant [NS])

- Length of stay: 3 days for TAVR vs. 7 days for SAVR (p < 0.001)

- Permanent pacemaker within 30 days: 6.5% for TAVR vs. 4.0% for SAVR (p = NS)

Computed tomography (CT) subanalysis: 408 patients were in the CT subanalysis cohort, of whom 384 had evaluable scans: TAVR 165, SAVR 119. At 30 days, the incidence of hypoattenuated leaflet thickening (HALT) was 13.3% vs. 5.0% (p = 0.03); at 1 year, the incidence was 27.5% vs. 20.2%. The vast majority of times (70-80%), HALT was noted on 1 out of 3 leaflets. All evaluable CTs showing HALT also noticed reduced leaflet motion. Patients with HALT had slightly higher gradients at 30 days (13.2 vs. 11.7 mm Hg, p = 0.08) and at 1 year (13.7 vs. 12.6 mm Hg, p = 0.24). About 56% of patients with HALT at 30 days had resolution at 1 year even without anticoagulation. Approximately 21% of patients without HALT at 30 days developed HALT at 1 year. Between days 7 and 35 post-implant, HALT patients had a nonsignificantly higher risk of thromboembolic events (8.6% vs. 2.9%, p = 0.11).

Health status:At 1 month, there was a large improvement in health status with TAVR (16-point difference in KCCQ-OS favoring TAVR vs. SAVR, p < 0.001). At 6 months, there was a modest improvement in health status with TAVR (2.6-point difference in KCCQ-OS favoring TAVR vs. SAVR, p < 0.04), and at 12 months, there was a modest improvement in health status with TAVR (1.8-point difference in KCCQ-OS favoring TAVR vs. SAVR, p < 0.04).

Interpretation

Among low-risk patients with aortic stenosis, TAVR was superior to SAVR at preventing death, stroke, or rehospitalization at 1 year. TAVR was also associated with a lower incidence of stroke and atrial fibrillation, and a shorter hospital length of stay compared with SAVR. TAVR was also associated with a larger improvement in quality of life compared with SAVR. There was a numerical increase in the need for new permanent pacemaker within 30 days in the TAVR group (6.5% with TAVR vs. 4.0% with SAVR); however, this difference was not statistically significant. Mild paravalvular aortic regurgitation occurred at a higher incidence in the TAVR group. The incidence of moderate to severe aortic regurgitation was rare (<1%) and similar between treatment groups. HALT was higher with TAVR compared with SAVR at 30 days, but not at 1 year. HALT appeared to be a dynamic process and spontaneously resolved in >50% of patients by 1 year, with new HALT appearing in 21% at 1 year.

This is a landmark trial, which will expand the penetration of TAVR in the treatment of aortic stenosis. Planned future research will examine long-term outcomes and valve durability, including the impact of HALT.

References

1. Baron SJ, Magnuson EA, Lu M, et al., on behalf of the PARTNER 3 Investigators. Health Status After Transcatheter vs. Surgical Aortic Valve Replacement in Low-Risk Patients With Aortic Stenosis.J Am Coll Cardiol2019;Sep 29:[Epub ahead of print].

2. Mack MJ, Leon MB, Thourani VH, et al., on behalf of the PARTNER 3 Investigators. Transcatheter Aortic-Valve Replacement With a Balloon-Expandable Valve in Low-Risk Patients.N Engl J Med2019;380:1695-1705.

3. Editorial:Otto CM. Informed Shared Decisions for Patients With Aortic Stenosis.N Engl J Med2019;380:1769-70.