PARTNER B

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Leon MB, et al. "Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery". The New England Journal of Medicine. 2010. 363(17):1597-1607.
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Clinical Question

In patients with severe AS who are poor surgical candidates, does transcatheter aortic-valve implantation reduce all-cause mortality and rehospitalization rates when compared to standard care?

Bottom Line

In patients with severe AS who are poor surgical candidates, transcatheter aortic-valve implantation reduces all-cause mortality and rates of rehospitalization for valve or procedure-related deterioration when compared to standard therapy, at the expense of more strokes.

Major Points

Surgical valve replacement reduces mortality in patients with symptomatic AS.[1] However, the condition often presents at an advanced age when patients are poor surgical candidates from comorbidities. Balloon valvuloplasty is a temporizing measure that may improve symptoms in the short-term though is associated with increased stroke and other complications. Transcatheter aortic-valve implantation (TAVI) is a procedure thought to be a reasonable alternative to surgical valve replacements as the implantation procedure is much less invasive. No large randomized trial had demonstrated its efficacy or safety in patients with AS thought to be poor surgical candidates.

The 2010 Placement of Aortic Transcatheter Valves, cohort B (PARTNER B) trial randomized 358 patients with severe AS thought to be poor surgical candidates to TAVI or standard medical therapy. TAVI was associated with lower rates of all-cause mortality at 1 year (30.7% vs. 49.7%; NNT 5) as well as the composite endpoint of all-cause mortality or repeat hospitalization for valve or procedure-related deterioration at 1 year (42.5% vs. 70.4%; NNT 4). However, TAVI was associated with increased complications including TIA or stroke at 1 year (10.6% vs. 4.5%; NNH 16) and major bleeding at 1 year (22.3% vs. 11.2%; NNH 9). The authors relate that the bleeding events may be related to the size of the femoral access sheaths. 5-year follow up [2] confirmed the mortality benefit.

The trial has been criticized for the high rate of balloon valvuloplasty in the standard therapy group (83.8%), a procedure with a class III recommendation in the absence of planned surgical intervention is not planned.[3][4]

The related PARTNER A trial[5] compared high-risk patients still candidates for surgery to TAVI or open AV replacement. There was no difference between surgery groups at 5 years.[6]

Guidelines

ACC/AHA Valvular Heart Disease[7] (2014, adapted)

  • Surgical AVR if low- or intermediate-risk for surgery and indication for AVR (class I, level A)
  • TAVR if indication for AVR but ""prohibitive risk"" for surgical AVR and predicted post-TAVR survival >12 months (class I, level B)
  • TAVR if indication for AVR but high surgical risk for surgical AVR (class IIa, level B)
  • Percutaneous aortic balloon dilation as bridge to surgical AVR or TAVR (class IIb, level C)

Design

  • Prospective, multicenter, randomized, open-label, comparative trial
  • N=358
    • TAVI (n=179)
    • Standard therapy (n=179)
  • Setting: 21 centers, 17 of which were in the US
  • Enrollment: 2007-2009
  • Median follow-up: 1.6 years
  • Analysis: Intention-to-treat
  • Primary outcomes:
    • All-cause mortality
    • All-cause mortality or time to first repeat hospitalization for valve or procedure-related deterioration

Population

Inclusion Criteria

  • Severe AS as defined by any of the following:
    • Aortic valve area <0.8 cm2 or AVA index <0.5 cm2/m2
    • Mean aortic valve gradient ≥40 mmHg
    • Peak aortic jet velocity of ≥4 m/sec
  • NYHA II, III, or IV symptoms
  • Poor surgical candidate by any of the following (confirmed by ≥2 surgeons):
    • STS risk score ≥10% (out of 100%, higher is greater surgical risk)
    • Coexisting conditions with ≥15% 30 day post-op risk of death
    • Coexisting conditions with ≥50% 30 day post-op risk of death or a "serious irreversible condition"

Exclusion Criteria

  • Unicuspid, bicuspid, or non-calcified AV
  • MI in the prior month or CAD requiring revascularization
  • Stroke or TIA in prior 6 months
  • AS and aortic regurgitation mixed disease with regurgitation with severity >3+
  • Invasive cardiac procedures in the prior 30 days
  • DES placed in prior 6 months
  • Any prior prosthetic valve or ring
  • Severe mitral annular calcification
  • MR with severity >3+
  • Leukopenia, anemia, thrombocytopenia, coagulopathy, or bleeding diathesis
  • Requirement for inotropes or devices to support mechanical hemodynamics
  • Need for emergency surgery
  • HCM
  • LVEF <20%
  • Thrombus, vegetation, or intracardiac mass
  • PUD or UGIB in previous 3 months
  • ASA, heparin, ticlopidine, clopidogrel, or contrast media sensitivities that would not be amenable to pre-medication
  • Aortic annulus <18 mm or >25 mm
  • Creatinine >3 mg/dL
  • Life expectancy <1 year for non-cardiac conditions
  • Aortic disease
  • Iliofemoral anatomy precluding sheath placement
  • Participation in another study for medications or devices
  • An active infection
  • Aortic valve leaflets with bulky calcifications close to coronary ostia

Baseline Characteristics

From the TAVI group.

  • Demographics: Age 83.1 years, male 45.8
  • PMH: CAD 67.6%, MI 18.6%, cerebrovascular disease 27.4%, PVD 30.3%, COPD 41.3% (requiring O2 21.2%), A-fib 32.9%, pulmonary HTN 42.4%, "frailty" 18.1%, liver disease 3.4%
  • PSH: CABG 37.4%, PCI 30.5%, balloon aortic valvuloplasty 16.2%, PPM 22.9%
  • Logistic EuroSCORE: 26.4% TAVI vs. 30.4% standard therapy (P=0.04; risk for cardiac surgery, out of 100%, >20% is very high risk)
  • Aorta with extensive calcifications: 19.0%
  • Chest wall deformity: 8.4%
  • Echocardiographic findings: Aortic valve area 0.6 cm2, aortic valve gradient 44.5 mmHg, moderate or severe MR 22.2%
  • NYHA class: II 7.8%, III or IV 92.2%
  • Labs: Creatinine >2 mg/dL 5.6%

Interventions

  • Randomization to a group:
    • TAVI - Esophageal echocardiographically-guided, femoral artery approach, percutaneous placement of a trileaflet bovine valve with stainless steel support frame deployed by balloon during rapid RV pacing
      • Heparin was used periprocedurally
      • ASA and clopidgorel were continued for 6 months
    • Standard therapy - Usual therapy as directed by the treatment team

Outcomes

Presented as TAVI vs. standard therapy.

Primary Outcome

All-cause mortality
30 days: 5.0% vs. 2.8% (P=0.41)
1 year: 30.7% vs. 49.7% (P<0.001; NNT 5)
2 years: Percentages not given (HR 0.55; 95% CI 0.40-0.74; P<0.001)
All-cause mortality or repeat hospitalization for valve or procedure-related deterioration
30 days: 10.6% vs. 12.3% (P=0.74)
1 year: 42.5% vs. 70.4% (P<0.001; NNT 4)
2 years: Percentages not given (HR 0.46; 95% CI 0.35-0.59; P<0.001)

Secondary Outcomes

CV mortality
30 days: 4.5% vs. 1.7% (P=0.22)
1 year: 19.6% vs. 41.9% (P<0.001; NNT 4)
2 years: Percentages not given (HR 0.39; 95% CI 0.27-0.56; P<0.001)
Repeat hospitalization for valve or procedure-related deterioration
30 days: 5.6% vs. 10.1% (P=0.17)
1 year: 22.3% vs. 44.1% (P<0.001; NNT 5)
TIA or stroke
30 days: 6.7% vs. 1.7% (P=0.03; NNH 20)
1 year: 10.6% vs. 4.5% (P=0.04; NNH 16)
TIA at 30 days: 0% vs. 0%
TIA at 1 year: 0.6% vs. 0% (P=1.00)
Minor stroke at 30 days: 1.7% vs. 0.6% (P=0.62)
Minor stroke at 1 year: 2.2% vs. 0.6% (P=0.37)
Major stroke at 30 days: 5.0% vs. 1.1% (P=0.06)
Major stroke 1 year: 7.8% vs. 3.9% (P=0.18)
All-cause mortality or major stroke
30 days: 8.4% vs. 3.9% (P=0.12)
1 year: 33.0% vs. 50.3% (P=0.001; NNT 6)
2 years: Percentages not given (HR 0.58; 95% CI 0.43-0.78; P<0.001)
MI
30 days: 0% vs. 0%
1 year: 0.6% vs. 0.6% (P=1.00)
Vascular complications
Any at 30 days: 30.7% vs. 5.0% (P<0.001; NNH 4)
Any at 1 year: 32.4% vs. 7.3% (P<0.001; NNH 4)
Major at 30 days: 16.2% vs. 1.1% (P<0.001; NNH 7)
Major at 1 year: 16.8% vs. 2.2% (P<0.001; NNH 7)
AKI
Creatinine >3 mg/dL at 30 days: 0% vs. 0.6% (P=1.00)
Creatinine >3 mg/dL at 1 year: 1.1% vs. 2.8% (P=0.45)
RRT at 30 days: 1.1% vs. 1.7% (P=1.00)
RRT at 1 year: 1.7% vs. 3.4% (P=0.50)
Major bleeding
30 days: 16.8% vs. 3.9% (P<0.001; NNH 8)
1 year: 22.3% vs. 11.2% (P=0.007; NNH 9)
Cardiac reintervention
Balloon aortic valvuloplasty at 30 days: 0.6% vs. 1.1% (P=1.00)
Balloon aortic valvuloplasty at 1 year: 0.6% vs. 36.9% (P<0.001; NNT 3)
Repeat TAVI at 30 days: 1.7% vs. n/a
Repeat TAVI at 1 year: 1.7% vs. n/a
Aortic valve replacement at 30 days: 0% vs. 1.7% (P=0.25)
Aortic valve replacement at 1 year: 1.1% vs. 9.5% (P<0.001; NNT 12)
Endocarditis
30 days: 0% vs. 0%
1 year: 1.1% vs. 0.6% (P=0.31)
New A-fib
30 days: 0.6% vs. 1.1% (P=1.00)
1 year: 0.6% vs. 1.7% (P=0.62)
New PPM
30 days: 3.4% vs. 5.0% (P=0.60)
1 year: 4.5% vs. 7.8% (P=0.27)

Subgroup Analysis

No significant interactions were found for age ≤ or >85 years, sex, BMI ≤ or >25 kg/m2, STS score ≤ or >11, LVEF ≤ or >55%, PMH of pulmonary HTN, moderate or severe mitral regurgitation, O2-dependent COPD, or PVD.

Criticisms

  • Excluded specific groups that would likely benefit from the procedure, including those with CAD, severe PVD, and LVEF <20%[8]
  • Limited follow-up to evaluate for duration of benefit
  • Likely higher rate of complications in the TAVI group given that the procedure is novel
  • Unknown durability of the valves used in TAVI[9]
  • Unclear if any improvement in quality of life[9]
  • The standard therapy involved the ineffective, ""dangerous,"" class III procedure, aortic valvuloplasty in 84% of the standard therapy patients and the benefits derived from TAVI may actually reflect increased harm from the high rate of valvuloplasty[3]
  • The standard therapy had a statistically higher EuroSCORE percentage than the TAVI group, a characteristic that may have influenced worsened outcomes[3]
  • Unclear cost effectiveness of TAVI[3]

Funding

Edward Lifesciences, makers of the SAPIEN heart-valve system used in this trial.

Further Reading

  1. Schwarz F, et al. "The effect of aortic valve replacement on survival." Circulation. 1982;66(5):1105-1110.
  2. Kapadia SR, et al. "5-year outcomes of transcatheter aortic valve replacement compared with standard treatment for patients with inoperable aortic stenosis (PARTNER 1): a randomised controlled trial." The Lancet. 2015;385(9986):2485-2491.
  3. 3.0 3.1 3.2 3.3 Multiple authors. "Correspondence: Transcatheter aortic-valve implantation for aortic stenosis." The New England Journal of Medicine. 2011;364:179-181.
  4. Bonow RO et al. "ACC/AHA guidelines for the management of patients with valvular heart disease: A report of the American College of Cardiology/American Heart Association Task Force on practice guidelines (Committee on management of patients with valvular heart disease)." Journal of the American College of Cardiology. 1998;32(5): 1486-1582.
  5. Smith CR et al. "Transcatheter versus surgical aortic-valve replacement in high-risk patients." The New England Journal of Medicine. 2011;364:2184-2198.
  6. Mack MJ, et al. "5-year outcomes of transcatheter aortic valve replacement or surgical aortic valve replacement for high surgical risk patients with aortic stenosis (PARTNER 1): a randomised controlled trial." The Lancet. 2015;385:2477-2484.
  7. Nishimura RA, et al. ""2014 AHA/ACC guideline for the management of patients with valvular heart disease."" Circulation 2013;Mar ePub.
  8. George JC et al. "Transcatheter aortic valve implantation: Lessons from the PARTNER (Placement of Aortic Transcatheter Valves) trial." JACC Cardiovascular Interventions. 2011;4(1):132-133.
  9. 9.0 9.1 Lazar, HL. ""Editorial: Transcatheter aortic valves -- Where do we go from here?"" The New England Journal of Medicine. 2010;363:1667-1668