PARTNER A

Published

Smith CR, et al. "Transcatheter versus Surgical Aortic-Valve Replacement in High-Risk Patients". The New England Journal of Medicine. 2011. 364(23):2187-98.
PubMed • Full text • PDF

Clinical Question

In patients with symptomatic severe AS who are high-risk surgical candidates (expected periprocedural mortality ~ 15%), is transcatheter aortic-valve implantation (TAVI) noninferior to surgical aortic valve replacement (AVR) with regard to all-cause mortality?

Bottom Line

In patients with symptomatic severe AS who are high-risk surgical candidates (expected periprocedural mortality ~ 15%), TAVI was associated with similar all-cause mortality to surgical AVR at 1 year.

Major Points

It is well-accepted that aortic valve replacement prolongs survival in patients with severe aortic stenosis (AS). However, the condition often presents at an advanced age when patients are poor surgical candidates due to multiple comorbidities. Transcatheter aortic valve implantation (TAVI) is an emerging technology whereby a self-expanding aortic valve prosthesis is inserted using a transcatheter approach. The PARTNER B trial established the role of TAVI in patients with severe AS who are not surgical candidates due to cormorbidity, as TAVI led to an absolute 20% reduction in all-cause mortality at 1 year with TAVI versus medical therapy. Given its inherently less invasive design, the benefit of TAVI may extend to patients who remain surgical candidates but are nevertheless at high risk for periprocedural complications.

The 2011 Placement of Aortic Transcatheter Valves, cohort A (PARTNER A) trial randomized 699 patients with symptomatic severe AS at high perioperative risk (estimated perioperative mortality ~ 15%) to TAVI or surgical AVR. At 1 year, the primary endpoint of all-cause mortality was 2% lower in the TAVI group, meeting prespecified criteria for noninferiority (superiority not established). However, TAVI was associated with a borderline statistically significant (p=0.07) 3% absolute increase in major stroke at 1 year as well as a 15% increase in vascular complications. A composite outcome of all-cause mortality or major stroke showed very similar outcomes with TAVI and surgical AVR. In addition, patients in both groups had similar improvements in 6-minute walk distance and NYHA class at 1 year. Importantly, comparative outcomes with TAVI vs. surgical AVR stratified by access approach (transfemoral vs. transapical) were similar, although the transapical subgroup was underpowered. Complications more prevalent with open AVR included a 10% higher rate of major bleeding and a borderline statistically significant (p=0.07) 5% higher rate of new atrial fibrillation. Patients who received TAVI had an ICU length of stay that was 2 days shorter and an overall hospitalization that was 4 days shorter.

Based largely on the results of PARTNER A, TAVI is now generally accepted as an appropriate alternative to surgical AVR in patients at high risk for operative complications. Notably, the 5 year results of PARTNER A were published in 2015 and continue to show no difference in mortality with TAVI versus open AVR, although there was a 10% increase in prevalence of severe aortic regurgitation, a complication for which careful monitoring is required in all TAVI patients and reintervention may be required.

Guidelines

ACC/AHA Valvular Heart Disease (2014, adapted)

• Surgical AVR if low- or intermediate-risk for surgery and indication for AVR (class I, level A)
• TAVI if indication for AVR but "prohibitive risk" for surgical AVR and predicted post-TAVI survival >12 months (class I, level B)
• TAVI 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 TAVI (class IIb, level C)

Design

• Prospective, multicenter, randomized, open-label, comparative trial
• N=699
  • TAVI (n=348)
  • Surgical AVR (n=351)
• Setting: 25 centers in US, Canada, Germany
• Enrollment: May 11, 2007 - August 28, 2009
• Median follow-up: 1.4 years
• Analysis: Intention-to-treat
• Primary outcome: All-cause mortality at 1 year

Population

Inclusion Criteria

• Severe AS defined as:
  • Aortic valve area <0.8 cm² AND either of:
    • Mean aortic valve gradient ≥40 mmHg
    • Peak aortic jet velocity of ≥4 m/sec
• NYHA II, III, or IV symptoms
• Surgical candidate for surgical AVR
• High-risk for operative complications defined as either of:
  • Coexisting conditions with ≥15% 30 day post-op risk of death
  • STS risk score ≥10 (out of 100, higher is greater surgical risk)

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 with or without obstruction
• 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 (transfemoral subjects only)
• 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 84 years, male 57.8%
• Risk Indices: STS score 11.8, EuroSCORE 29.3
• Cardiac History: NYHA II 5.7%, NYHA III or IV 94.3%, CAD 74.9%, Previous MI 26.8%, Previous CABG 42.6%, Previous PCI 34.0%, AF 40.8%, PPM 20.0%, Pulm HTN 42.4%, LVEF 52.5%, moderate or severe MR 19.8%
• Other Comorbidities: Cerebrovascular disease 29.3%, PAD 43%, COPD 43.4%, CKD 11.1%, Frailty 15.6%, Liver disease 2.0%
• Aortic Valve: AVA 0.7cm2, Mean gradient 42.7mmHg

Interventions

• At enrollment, patients underwent mapping to determine candidacy for transfemoral vs. transapical TAVI approach
• Subjects then underwent 1:1 randomization stratified by planned approach (transfemoral vs. transapical) to:
  • TAVI - Esophageal echocardiographically-guided, 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
  • Surgical AVR - Surgical aortic valve replacement
• Major outcomes assessed at 30 days and 1 year by blinded outcome adjudicators

Outcomes

Presented as TAVI vs. surgical AVR.

Primary Outcome

All-cause mortality

30 days: 3.4% vs. 6.5% (P=0.07)

1 year: 24.2% vs. 26.8% (P=0.44)

Secondary Outcomes

Stroke or TIA

30 days: 5.5% vs. 2.4% (P=0.04)

1 year: 8.3% vs. 4.3% (P=0.04)

Major stroke

30 days: 3.8% vs. 2.1% (P=0.20)

1 year: 5.1% vs. 2.4% (P=0.07)

All-cause mortality or major stroke

30 days: 6.9% vs. 8.2% (P=0.52)

1 year: 26.5% vs. 28.0% (P=0.68)

Vascular complication

30 days: 17.0% vs. 3.8% (P<0.001)

1 year: 18.0% vs. 4.8% (P<0.001)

Major bleeding

30 days: 9.3% vs. 19.5% (P<0.001)

1 year: 14.7% vs. 25.7% (P<0.001)

Subgroup Analysis

All analysis are for primary outcome of all-cause mortality

Sex (interaction p=0.05)

Male: 28.4% vs. 24.2% (HR=1.17; 95% CI 0.84-1.63)

Female: 18.4% vs. 27.2% (HR=0.68; 95% CI 0.44-1.04)

Previous CABG (interaction p=0.02)

No Previous CABG: 22.2% vs. 30.7% (HR=0.72; 95% CI 0.52-1.01)

Previous CABG: 25.9% vs. 19.1% (HR=1.35; 95% CI 0.88-2.08)

Access Approach (interaction p=0.43)

Transapical: 28.8% vs. 26.2% (HR=1.10; 95% CI 0.71-1.71)

Transfemoral: 22.1% vs. 25.0% (HR=0.89; 95% CI 0.64-1.22)

Criticisms

• Excluded specific groups that may benefit from TAVI, including those with CAD, severe PVD, and LVEF <20%
• Significant (4.6%) crossover to surgical AVR in the TAVI group, which may have biased toward noninferiority of TAVI
• Actual surgical mortality at 30 days was 3% lower than expected by STS score, potentially limiting power to detect superiority of TAVI over surgical AVR

Funding

• Study sponsor and maker of SAPIEN XT valve Edward Lifesciences designed, funded, participated in selection and management of sites, collection of data, and data monitoring.
• Study sponsor statistician performed the primary analysis.