Journal of the American College of Cardiology (JACC) MARCH 30, 2025

Evolut Low Risk Trial: Transcatheter Aortic Valve Replacement (TAVR) vs. Surgical Aortic Valve Replacement (SAVR) in Low-Risk Patients

John K. Forrest, Steven J. Yakubov, G. Michael Deeb, et al.

Bottom Line

In patients with severe symptomatic aortic stenosis at low surgical risk, TAVR with a self-expanding bioprosthesis demonstrated noninferiority to SAVR for the primary endpoint of all-cause mortality or disabling stroke at 24 months, with outcomes remaining comparable through 5-year follow-up.

Key Findings

1. At 24 months, the primary composite endpoint of all-cause mortality or disabling stroke occurred in 5.3% of the TAVR group versus 6.7% in the SAVR group (noninferior).
2. At 5 years, the incidence of the primary composite endpoint remained comparable at 15.5% for TAVR versus 16.4% for SAVR (HR 0.90; P=0.47).
3. TAVR patients demonstrated superior hemodynamic performance with significantly lower mean aortic valve gradients and larger effective orifice areas compared to SAVR at follow-up intervals.
4. TAVR was associated with higher rates of permanent pacemaker implantation (e.g., 23.8% vs 9.7% at 4 years) and increased incidence of moderate-to-severe paravalvular leak compared to surgery.
5. SAVR was associated with higher rates of new-onset atrial fibrillation, acute kidney injury, and severe bleeding during the perioperative period.

Study Design

Design
RCT
N/A
Sample
1,414
Patients
Duration
5 yr
Median
Setting
Multicenter, International
Population Patients with severe symptomatic aortic stenosis and a predicted 30-day surgical mortality risk of less than 3% as assessed by a local heart team.
Intervention Transcatheter Aortic Valve Replacement (TAVR) using self-expanding bioprosthetic valves (CoreValve, Evolut R, or Evolut PRO).
Comparator Surgical Aortic Valve Replacement (SAVR) with a bioprosthetic valve.
Outcome Composite of all-cause mortality or disabling stroke at 24 months.

Study Limitations

The primary endpoint excludes rehospitalization, which may be a critical factor for younger, low-risk patients.
The trial observed higher rates of permanent pacemaker implantation and potential concerns regarding long-term structural valve durability and reintervention rates that warrant extended monitoring.
Early iterations of the self-expanding valves (CoreValve/Evolut R/PRO) used in the trial are no longer the most current generation of devices, potentially limiting generalizability to newer technologies.
While 5-year data are robust, the long-term lifetime management of these patients remains a significant, ongoing clinical question.

Clinical Significance

The trial provides evidence that TAVR is a viable, safe, and effective alternative to surgery for patients with severe aortic stenosis who are at low surgical risk, supporting the expansion of TAVR usage in younger, lower-risk patient populations while highlighting the necessity of individualized heart team decision-making.

Historical Context

The Evolut Low Risk trial was initiated to challenge the 'gold standard' of surgical aortic valve replacement in patients with low surgical risk, following successful outcomes in high- and intermediate-risk cohorts. It was published in parallel with similar landmark evidence from the PARTNER 3 trial, fundamentally shifting global guidelines toward broader adoption of TAVR.

Guided Discussion

High-yield insights from every perspective

Med Student
Medical Student

What is the primary hemodynamic advantage of a supra-annular self-expanding TAVR valve over a traditional surgical bioprosthesis, and how does this translate to clinical outcomes in patients with small aortic annuli?

Key Response

Self-expanding valves like the Evolut sit above the native annulus (supra-annular). This allows for a larger effective orifice area (EOA) and lower transvalvular gradients compared to stented surgical valves, which must fit within the annulus. Clinically, this reduces the risk of prosthesis-patient mismatch (PPM), a condition where the valve is too small for the patient's body surface area, leading to persistent symptoms and increased mortality.

Resident
Resident

A 65-year-old active male with an STS risk score of 1.2% is diagnosed with severe symptomatic aortic stenosis. While the Evolut Low Risk trial shows noninferiority for TAVR vs. SAVR, what specific procedural complication occurs more frequently in the TAVR group that might influence his long-term morbidity?

Key Response

The Evolut Low Risk trial demonstrated that TAVR has a significantly higher rate of permanent pacemaker implantation (PPI) compared to SAVR (approximately 17-20% vs. 1-2%). In a younger, low-risk patient, the long-term consequences of chronic right ventricular pacing, such as pacing-induced cardiomyopathy and the need for multiple generator changes over their lifetime, must be weighed against the faster recovery offered by TAVR.

Fellow
Fellow

Considering the 5-year results of the Evolut Low Risk trial, how do the trends in structural valve deterioration (SVD) and hemodynamic performance compare between the self-expanding TAVR and SAVR cohorts, and what are the implications for 'lifetime management' in patients under 70?

Key Response

Five-year data showed that TAVR maintained significantly lower mean gradients (approx. 9 mmHg vs 12 mmHg) and larger EOAs than SAVR. Notably, the rate of SVD was lower in the TAVR arm. However, 'lifetime management' is complex because a TAVR-first strategy in a 65-year-old necessitates a future TAVR-in-TAVR or a high-risk surgical explant, and the high frame of the Evolut can make future coronary access for CAD management more difficult.

Attending
Attending

The Evolut Low Risk trial excluded patients with bicuspid aortic valves. How should this exclusion affect our clinical application of these results given that bicuspid morphology is the most common cause of AS in the 'low risk' younger demographic?

Key Response

Attending-level practice requires recognizing that 'low risk' in trials is often defined by STS score, not anatomy. Bicuspid valves often have asymmetric calcification, larger annuli, and associated aortopathy, which were not captured in this trial. Therefore, while TAVR is noninferior in tricuspid low-risk patients, SAVR remains the gold standard for most bicuspid patients until dedicated long-term randomized data for TAVR in bicuspid anatomy is available.

Scholarly Review

Critical appraisal through the lens of expert reviewers and guideline development

PhD
PhD

The Evolut Low Risk trial utilized a Bayesian adaptive design with a noninferiority margin of 6%. What are the methodological advantages of using a Bayesian approach in this context, and how might the choice of the 6% margin be critiqued in a low-risk population where event rates are inherently low?

Key Response

The Bayesian design allowed for interim analyses to potentially stop the trial early for success, optimizing sample size. However, a 6% noninferiority margin for a composite endpoint of death or disabling stroke is relatively wide when the expected baseline event rate in low-risk patients is also low. Critics argue that such a margin might allow for a clinically significant disadvantage in one arm to be statistically masked as 'noninferior'.

Journal Editor
Journal Editor

The primary endpoint of the Evolut Low Risk trial is a composite of all-cause mortality and disabling stroke. If you were reviewing the 5-year follow-up, how would you evaluate the 'win ratio' or the hierarchical importance of these events, and what concerns would you raise regarding the potential for attrition bias in the SAVR arm?

Key Response

Editors look for 'fragility' in the data. Because TAVR patients often have shorter hospital stays and fewer initial complications, there may be differential follow-up or 'crossover' perception. Furthermore, as a composite, the mortality benefit must be teased out from the stroke benefit to ensure one isn't carrying the other. If the mortality curves diverge later, the editor must ensure the study was powered for late-term individual components, not just the early composite.

Guideline Committee
Guideline Committee

Current ACC/AHA guidelines (2020) recommend SAVR for patients <65 years and TAVR/SAVR shared decision-making for those 65-75. Does the 5-year Evolut Low Risk data provide sufficient evidence to lower the Class 1 TAVR recommendation to age <65, and how should the guidelines address the discrepancy between TAVR's superior hemodynamics and higher pacemaker rates?

Key Response

The committee must balance Level of Evidence (LOE) A data for 5-year durability against the lack of 10-15 year data. While TAVR's hemodynamics are superior (supporting a lower age threshold), the PPI rate remains a significant hurdle for patients with long life expectancies. Current guidelines prioritize SAVR in the very young (<65) due to the known long-term durability of surgical bioprostheses (15+ years) and the ease of future TAVR-after-SAVR compared to the challenges of TAVR-after-TAVR.

Clinical Landscape

Noteworthy Related Trials

2010

PARTNER 1A Trial

n = 699 · NEJM

Tested

Transcatheter Aortic Valve Replacement (TAVR)

Population

Patients with severe aortic stenosis deemed at high surgical risk

Comparator

Surgical Aortic Valve Replacement (SAVR)

Endpoint

All-cause mortality at 1 year

Key result: TAVR was non-inferior to surgical replacement in high-risk patients, with 1-year mortality rates of 24.2% and 26.8% respectively.
2017

SURTAVI Trial

n = 1746 · NEJM

Tested

Transcatheter Aortic Valve Replacement (TAVR) with CoreValve or Evolut R

Population

Patients with severe aortic stenosis at intermediate surgical risk

Comparator

Surgical Aortic Valve Replacement (SAVR)

Endpoint

Composite of all-cause mortality or disabling stroke at 24 months

Key result: TAVR was found to be non-inferior to surgical replacement for intermediate-risk patients with a primary endpoint rate of 12.6% versus 14.0%.
2019

PARTNER 3 Trial

n = 1000 · NEJM

Tested

Transcatheter Aortic Valve Replacement (TAVR) with Sapien 3

Population

Patients with severe aortic stenosis at low surgical risk

Comparator

Surgical Aortic Valve Replacement (SAVR)

Endpoint

Composite of death, stroke, or rehospitalization at 1 year

Key result: TAVR was superior to SAVR with a rate of the primary endpoint of 8.5% in the TAVR group versus 15.1% in the surgical group.

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