Placement of Aortic Transcatheter Valves 3 - PARTNER 3

Nov 05, 2021
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Author/Summarized by Author:
Anthony A. Bavry, MD, MPH, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, FACC
Summary Supplemental Reviewer:
Dharam J. Kumbhani, MD, SM, FACC
Trial Sponsor:
Edwards Lifesciences
Date Presented:
11/05/2021
Date Published:
09/29/2019
Date Updated:
11/05/2021
Original Posted Date:
03/17/2019
References

Contribution To Literature:

Highlighted text has been updated as of November 5, 2021.

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).

2-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)

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 2 years. 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. TAVR vs. SAVR was associated with an increased incidence of valve thrombosis (VARC-2 definition) and increased mean transvalvular gradient at 2 years. 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:

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: Arrhythmias and Clinical EP, Cardiac Surgery, Geriatric Cardiology, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Valvular Heart Disease, Atrial Fibrillation/Supraventricular Arrhythmias, Aortic Surgery, Cardiac Surgery and Arrhythmias, Cardiac Surgery and Heart Failure, Cardiac Surgery and VHD, Acute Heart Failure, Interventions and Imaging, Interventions and Structural Heart Disease

Keywords: ACC Annual Scientific Session, acc20, ACC19, Aortic Valve Insufficiency, Aortic Valve Stenosis, Aspirin, Atrial Fibrillation, Cardiac Surgical Procedures, Geriatrics, Heart Failure, Heart Valve Diseases, Heart Valve Prosthesis, Pacemaker, Artificial, Stroke, Transcatheter Aortic Valve Replacement, Vascular Diseases, TCT19, TCT21, Tomography, Transcatheter Cardiovascular Therapeutics


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