SURTAVI

Published

Reardon MJ, et al. "Surgical or transcatheter aortic-valve replacement in intermediate-risk patients". The New England Journal of Medicine. 2017. epub 2017-03-17:1-11.
PubMed • Full text • PDF

Clinical Question

In patients with severe, symptomatic Aortic Stenosis (AS) at intermediate surgical risk, how does transcatheter aortic valve replacement (TAVR) compare to surgical aortic valve replacement (SAVR) in safety and efficacy?

Bottom Line

In patients with severe, symptomatic AS at intermediate surgical risk (3-15% risk of surgical death at 30 days per STS-PROM score), transcatheter aortic valve replacement (TAVR) was found to be non-inferior to surgical aortic valve replacement (SAVR) with respect to all-cause mortality and disabling stroke at 2 years. SAVR was associated with a marginally higher peri-operative stroke rate while TAVR was associated with a modest increase in hospitalizations related to aortic valvular disease at 2 years.

Major Points

TAVR (transcatheter aortic valve replacement) is an emerging therapy for severe AS in which an aortic valve prosthesis is inserted percutaneously rather than during via thoracotomy as in surgical aortic valve replacement (SAVR). The two TAVR valves in current use include the balloon-expandable Sapien XT valve and the self-expanding CoreValve. On the strength of landmark RCTs including PARTNER A, PARTNER B, and the Core Valve High Risk Study , TAVR has emerged as an acceptable alternative to SAVR in patients who are either not candidates for surgery or at high surgical risk. More recently, PARTNER 2 demonstrated that the balloon-expandable Sapien XT TAVR was noninferior to SAVR in patients even at only intermediate risk for surgery, with similar rates of a composite outcome of all-cause mortality or disabling stroke at 2 years. A similar trial demonstrating the comparative safety and efficacy of the self-expandable CoreValve TAVR to SAVR in intermediate-risk patients was needed.

The 2017 Surgical Replacement and Transcatheter Aortic Valve Implantation (SURTAVI) trial randomized 1660 patients at intermediate risk for surgical complications (3-15% risk of surgical death at 30 days per STS-PROM score) to either SAVR or TAVR with the self-expandable CoreValve and assessed for a primary composite outcome of all-cause mortality or disabling stroke. At 24 months, the primary outcome was met in 12.6% of patients randomized to TAVR versus 14.0% of patients randomized to SAVR (criteria for noninferiority of TAVR met), with similar rates of both stroke and all-cause mortality in both groups. SAVR was associated with a marginal absolute 2.2% increase in peri-operative stroke rates while TAVR was associated with a 3.5% absolute increase in hospitalizations related to aortic valvular disease at 2 years. Peri-operative complication profile varied between the two procedures, with a 30.5% increase in new/worsening AF and 19.3% increase in requirement for PPM with SAVR versus a 4.9% increase in vascular complications with TAVR.

In summary, SURTAVI adds to the growing body of evidence first established by PARTNER 2 suggesting that TAVR is an acceptable alternative to SAVR in patients with severe AS and intermediate risk of surgical complications with similar intermediate-term outcomes. In response to the findings of both studies, the ACA/AHA released a focused update in 2017 giving TAVR a class IIa indication (reasonable option) for severe AS in patients with intermediate surgical risk. Depending upon resource availability and operator experience, the decision between the two approaches should likely be made on a case-by-case basis with the assistance of an interdisciplinary heart team. Future studies designed to investigate the role of TAVR in patients with low surgical risk are underway.

Guidelines

The 2017 AHA/ACC Focused Update of the 2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease state:

TAVR is a reasonable alternative to surgical AVR for symptomatic patients with severe AS (Stage D) and an intermediate surgical risk, depending on patient-specific procedural risks, values, and preferences (class IIa)

Design

• Multinational, randomized noninferiority clinical trial at 87 centers
• N=1746
  • TAVI (n=864)
  • Surgical AVR (n=796)
• Setting: 87 centers in the United States, Europe and Canada
• Enrollment: June 19, 2012 to June 30, 2016
• Mean follow-up: 2 years
• Analysis: Intention-to-treat
• Primary outcome: All-cause mortality or disabling stroke at 2 years

Population

Inclusion Criteria

• Symptomatic, severe aortic stenosis
  • Severe aortic-valve stenosis defined as
    • NYHA class II or greater CHF
    • an initial aortic-valve area of 1.0cm² or less
    • an aortic-valve area index of less than 0.6 cm² per square meter of body-surface area and a mean gradient of more than 40 mm Hg
    • a maximum aortic velocity of more than 4 m per second at rest or with dobutamine provocation in patients with a left ventricular ejection fraction of less than 55% or a Doppler velocity index of less than 0.25 on resting echocardiography
• Determined by the local multidisciplinary heart team to be at intermediate surgical risk, defined as an estimated risk of 30-day surgical death of 3 to 15% according to the criteria of the Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM)

Exclusion Criteria

• MI within 30 days
• CVA or TIA within 6 months
• GI bleed within 3 months
• ESRD or GFR < 20mL/min
• PCI or peripheral arterial intervention including stent placement within 30 days (BMS) or 6 months (DES)
• Significant blood dyscrasias
• Untreated clinically significant CAD or PAD
• Cardiogenic shock or LVEF < 20%
• Active infection
• Life expectancy < 1 year
• Anatomic exclusions
  • Aortic regurgitation greater than 3+
  • Moderate to severe mitral stenosis or regurgitation
  • Severe tricuspid regurgitation
  • Hypertrophic obstructive cardiomyopathy
  • Echocardiographic evidence of intracardiac mass, thrombus, or vegetation
  • Bicuspid or unicuspid aortic valve or dilated aortic root

Baseline Characteristics

From the TAVR group

• Demographics: age 79.9, male 57.6%,
• Co-morbidity: NYHA II 39.8%, NYHA III 54.6%, NYHA IV 5.6%, STS-PROM 4.4, EuroSCORE 11.9, DM 34.1%, HTN 92.7%, CVA 6.6%, PAD 30.8%, PPM 9.7%, CAD 62.6%, arrhythmia 31.8%

Interventions

• Randomized 1:1 to surgical AVR versus CoreValve TAVR (16% received Evolute R bioprosthesis TAVR)
  • Randomization stratified according to clinical site and the need for surgical coronary revascularization
  • The choice and size of the surgical bioprosthesis were left to the discretion of the surgeon
  • Patients in the surgery group underwent coronary revascularization at the time of aortic-valve replacement if needed
  • Patients in the TAVR group underwent staged PCI either before or during TAVR if needed
• Patients deemend to be at intermediate risk for surgical mortality (see Inclusion Criteria) by local interdisciplinary heart team prior to randomization
• Transfemoral access was preferred although subclavian or direct aortic approaches used in patients with unsuitable anatomy
• Use of embolic protection not permitted
• Antiplatelet use as follows:
  • TAVR: DAPT for 3 months followed by aspirin indefinitely (in patients on anticoagulation at baseline, anticoagulation with a single antiplatelet agent indefinitely)
  • SAVR: Aspirin indefinitely (in patients on anticoagulation at baseline, anticoagulation with a single antiplatelet agent indefinitely)
• All patients were assessed for stroke by a trained neurologist and all events were adjudicated by a blinded independent committee (including echocardiographic outcomes)

Outcomes

Comparisons are TAVR vs. Surgery (Modified ITT)

Primary Outcomes

Death from any cause or disabling stroke at 24 months

12.6% vs. 14.0% (95% credible interval [Bayesian analysis] for difference, -5.2 to 2.3; posterior probability of noninferiority, >0.999)

Secondary Outcomes

All-cause death

11.4% vs. 11.6% (95% credible interval for difference, -3.8 to 3.3)

All stroke and TIA

10.0% vs. 11.0% (95% credible interval for difference, -4.2 to 2.2)

Major adverse cardiovascular events

18.6% vs. 18.6% (95% credible interval for difference, -4.2 to 2.2)

Hospitalization for aortic valve disease

13.2% vs. 9.7% (95% credible interval for difference, 0.1 to 7.0)

Moderate to severe residual paravalvular aortic regurgitation (1 year)

5.3% vs. 0.6% (95% credible interval for difference, 2.8 to 6.8)

Subgroup Analysis

• Prespecified subgroup analysis (including trial site and geographic region) revealed no significant effect modification with TAVR vs. SAVR with regard to the primary outcome

Adverse Events

Life-threatening or major bleeding (30 days)

12.2% vs 9.3% (95% credible interval for difference, -0.1 to 5.9)

Acute kidney injury stage 2 or 3 (30 days)

1.7% vs 4.4% (95% credible interval for difference, -4.4 to -1.0)

Major vascular complication (30 days)

6.0% vs 1.1% (95% credible interval for difference, 3.2 to 6.7)

Permanent pacemaker implantation (30 days)

25.9% vs 6.6% (95% credible interval for difference, 15.9 to 22.7)

Atrial fibrillation (30 days)

12.9% vs 43.4% (95% credible interval for difference, -34.7 to -26.4)

Criticisms

• Primary outcome rate of 12-14% at 2 years was slightly lower than expected (17%) which may reduce power to detect a statistical difference between TAVR and SAVR. Given direction of effect, one cannot rule out the possibility that TAVR is superior to SAVR in this population, although the trial was not designed to assess this hypothesis
• Given relatively limited duration of follow-up of 2 years, cannot rule out the possibility of differences in outcomes in SAVR vs. TAVR over longer-term follow-up

Funding

• Medtronic funded the trial and developed the protocol, Medtronic representatives were responsible for site selection, data monitoring, and trial management.