Placement of Aortic Transcatheter Valves 3 - PARTNER 3

Nov 27, 2023
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Author/Summarized by Author:
Anthony A. Bavry, MD, MPH, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, FACC; Kim A. Eagle, MD, MACC
Summary Supplemental Reviewer:
Dharam J. Kumbhani, MD, SM, FACC
Trial Sponsor:
Edwards Lifesciences
Date Presented:
10/24/2023
Date Published:
11/23/2023
Date Updated:
11/27/2023
Original Posted Date:
03/17/2019
References

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).

Two-Year outcomes:

  • Primary outcome: 11.5% with TAVR vs. 17.4% with SAVR (p = 0.007)
  • Death or disabling stroke: 3.0% with TAVR vs. 3.8% with SAVR (p = 0.47)
  • Rehospitalization: 8.5% with TAVR vs. 12.5% with SAVR (p = 0.046)
  • Valve thrombosis (Valve Academic Research Consortium-2 [VARC-2]): 2.6% with TAVR vs. 0.7% with SAVR (p = 0.02)
  • Mean transvalvular gradient: 13.6 mm Hg with TAVR vs. 11.8 mm Hg with SAVR (p < 0.001)
  • Mild paravalvular aortic insufficiency: 26.0% with TAVR vs. 2.3% with SAVR (p < 0.001)

Five-year outcomes:

  • Primary outcome: 22.8% with TAVR vs. 27.2% with SAVR (p = 0.07)
  • All-cause mortality: 10.0% with TAVR vs. 8.2% with SAVR (p = 0.35); cardiovascular mortality: 5.5% vs. 5.1% (p = 0.8)
  • Stroke: 5.8% with TAVR vs. 6.4% with SAVR (p = 0.6)
  • Rehospitalization: 13.7% with TAVR vs. 17.4% with SAVR (p = 0.09)
  • Atrial fibrillation: 13.7% with TAVR vs. 42.4% with SAVR (p < 0.05)
  • Serious bleeding: 10.2% with TAVR vs. 14.8% with SAVR (p < 0.05)
  • Valve thrombosis (Valve Academic Research Consortium-3 [VARC-3]): 2.5% with TAVR vs. 0.2% with SAVR (p < 0.05) (13 vs. 1 event; 7 out of 13 events in TAVR resolved with anticoagulation)
  • Repeat aortic valve intervention: 2.6% with TAVR vs. 3.0% with SAVR (p = 0.72)
  • Paravalvular regurgitation ≥ mild: 20.8% with TAVR vs. 3.2% with SAVR (p < 0.05)
  • Mean transvalvular gradient: 12.8 mm Hg with TAVR vs. 11.7 mm Hg with SAVR (p < 0.001)
  • Mild paravalvular aortic insufficiency: 19.9% with TAVR vs. 3.2% with SAVR (p < 0.001); moderate/severe paravalvular leak: 0.9% with TAVR vs. 0% with SAVR
  • Bioprosthetic valve failure: 3.3% with TAVR vs. 3.8% with SAVR (p = NS)
  • Mean Kansas City Cardiomyopathy Questionnaire-Overall Summary (KCCQ-OS) score: 86.2% with TAVR vs. 85.9% with SAVR (p = 0.99)
  • Valvulo-arterial impedance (ZVa): 3.51 vs. 3.78 mm Hg/mL/m2 with TAVR vs. SAVR (p < 0.01); ZVa >4 associated with higher risk of rehospitalization
  • Tricuspid annular plane systolic excursion (TAPSE): 1.95 vs. 1.51 cm with TAVR vs. SAVR (p < 0.0001)

Cost-effectiveness analysis: Index hospitalization costs for TAVR vs. SAVR: $47,196 vs. $46,606 (p = 0.59); additional 2-year follow-up costs: $19,638 vs. 22,258 (p = 0.13). Base-case analysis suggested that TAVR was cost-dominant 84% of the time, and had an incremental cost-effectiveness ratio (ICER) ≤50,000/quality-adjusted life-year 95% of the time (based on 2-year data).

Interpretation:

Among low-risk patients with aortic stenosis, TAVR was superior to SAVR at preventing death, stroke, or rehospitalization at 1 year. This benefit was sustained to 5 years. Mortality and strokes at 5 years were similar between the two modalities. TAVR was also associated with a lower incidence of 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 upfront, with similar values for the KCCQ-OS at 5 years. 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; however, this did not appear to be associated with worse clinical outcomes. The incidence of moderate to severe aortic regurgitation was rare (<1%) and similar between treatment groups.

At 5 years, adverse cardiovascular outcomes were similar between treatment groups. TAVR was associated with a lower incidence of atrial fibrillation and serious bleeding vs. SAVR. Compared with TAVR, SAVR was associated with a lower incidence of valve thrombosis and mild or greater paravalvular regurgitation. However, valve function (mean gradient) and bioprosthetic valve failure were 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.  Valve hemodynamics were similar out to 5 years (statistically significant by -1 mm Hg in favor of SAVR) and valve thrombosis (VARC-3 definition was higher with TAVR than SAVR; the majority of these episodes resolved with anticoagulation. On cost-effectiveness analysis, TAVR appeared to be cost-dominant in most scenarios (over a 2-year horizon). TAVR was also projected to be cost-effective over the long-term, as long as there are no differences in late mortality between TAVR and SAVR.

This is a landmark trial, which greatly helped expand the eligible patient population for TAVR as a treatment option for severe aortic stenosis. Planned future research will examine long-term outcomes and valve durability (10-year clinical and echocardiographic follow-up planned), including the impact of HALT.

References:

Highlighted text has been updated as of November 27, 2023.

Editorial: Landmesser U. The Changing Landscape of Aortic-Valve Stenosis Management. N Engl J Med 2023;389:2008-9.

Presented by Dr. Rebecca T. Hahn at the Transcatheter Cardiovascular Therapeutics meeting (TCT 2023), San Francisco, CA, October 24, 2023.

Mack MJ, Leon MB, Thourani VH, et al., on behalf of the PARTNER 3 Investigators. Transcatheter Aortic-Valve Replacement in Low-Risk Patients at Five Years. N Engl J Med 2023;389:1949-60.

Presented by Dr. Martin B. Leon at the Transcatheter Cardiovascular Therapeutics meeting (TCT 2023), San Francisco, CA, October 24, 2023.

Presented by Dr. David J. Cohen at the Transcatheter Cardiovascular Therapeutics (TCT) Conference, Orlando, FL, November 5, 2021.

Presented by Dr. Michael J. Mack at the American College of Cardiology Virtual Annual Scientific Session Together With World Congress of Cardiology (ACC 2020/WCC), March 29, 2020.

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 Cardiol 2019;74:2833-42.

Presented by Dr. Suzanne J. Baron at the Transcatheter Cardiovascular Therapeutics meeting (TCT 2019), San Francisco, CA, September 29, 2019.

Presented by Dr. Raj Makkar at the Transcatheter Cardiovascular Therapeutics meeting (TCT 2019), San Francisco, CA, September 27, 2019.

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 Med 2019;380:1695-1705.

Editorial: Otto CM. Informed Shared Decisions for Patients With Aortic Stenosis. N Engl J Med 2019;380:1769-70.

Presented by Dr. Martin Leon at the American College of Cardiology Annual Scientific Session (ACC 2019), New Orleans, LA, March 17, 2019.

Clinical Topics: Noninvasive Imaging, Echocardiography/Ultrasound, Invasive Cardiovascular Angiography and Intervention, Valvular Heart Disease

Keywords: TCT23, Transcatheter Cardiovascular Therapeutics, Stenosis, Aortic Disease, Echocardiography


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