New England Journal of Medicine APRIL 02, 2016

Transcatheter or Surgical Aortic-Valve Replacement in Intermediate-Risk Patients (PARTNER 2A)

Leon MB, Smith CR, Mack MJ, et al. for the PARTNER 2 Investigators

Bottom Line

In patients with severe symptomatic aortic stenosis at intermediate surgical risk, TAVR with a second-generation balloon-expandable valve was noninferior to surgical aortic valve replacement regarding the composite endpoint of all-cause mortality or disabling stroke at 2 years.

Key Findings

1. The primary composite endpoint of all-cause mortality or disabling stroke at 2 years occurred in 19.3% of the TAVR group versus 21.1% of the SAVR group (hazard ratio 0.89; 95% confidence interval, 0.73 to 1.09; p=0.25), meeting the prespecified noninferiority margin.

2. Transfemoral access, used in 76.3% of TAVR procedures, was associated with superior outcomes compared to surgery for the primary endpoint (16.8% vs. 20.4%).

3. TAVR was associated with higher rates of major vascular complications (7.9% vs. 5.0%, p=0.008) and moderate-to-severe paravalvular regurgitation (8.0% vs. 0.6%, p<0.001) at 2 years.

4. SAVR was associated with higher rates of new-onset atrial fibrillation (26.4% vs. 9.1%, p<0.001) and life-threatening bleeding (43.4% vs. 10.4%, p<0.0001) at 30 days.

Study Design

Design

RCT

Open-Label

Sample

2,032

Patients

Duration

2 yr

Median

Setting

Multicenter, US/Canada

Population Patients with severe symptomatic aortic stenosis deemed at intermediate surgical risk by a Heart Team (STS-PROM score 4-8%)

Intervention Transcatheter aortic valve replacement (TAVR) with a balloon-expandable (Sapien XT) valve

Comparator Surgical aortic valve replacement (SAVR)

Outcome Composite of all-cause mortality or disabling stroke at 2 years

Study Limitations

• The study utilized a second-generation balloon-expandable valve (Sapien XT) that has since been superseded by newer, improved generations with better sealing mechanisms.

• The high rate of moderate-to-severe paravalvular leak in the TAVR arm was a significant concern and remains a primary target for technical refinement.

• The trial included patients who required non-femoral access, where TAVR performance was numerically less favorable than surgery, potentially biasing overall results compared to contemporary transfemoral-first practices.

Clinical Significance

This landmark trial expanded the indication for TAVR beyond high-risk and inoperable patients to the intermediate-risk population, fundamentally changing clinical practice by establishing TAVR as a valid, less-invasive therapeutic alternative to surgical aortic valve replacement.

Historical Context

Following the success of the original PARTNER trial in high-risk patients, the PARTNER 2A trial served as the pivotal evidence needed to lower the risk-profile threshold for TAVR, reflecting the maturation of both transcatheter technology and operator proficiency.

Guided Discussion

High-yield insights from every perspective

Med Student

Medical Student

What is the primary pathophysiological difference between the mechanical approach of Surgical Aortic-Valve Replacement (SAVR) and Transcatheter Aortic-Valve Replacement (TAVR) for treating symptomatic aortic stenosis?

Key Response

Surgical replacement (SAVR) involves the physical excision of the calcified native valve leaflets and suturing a prosthetic valve onto the annulus under cardiopulmonary bypass. In contrast, TAVR is a less invasive approach where a collapsible prosthetic valve is delivered percutaneously and expanded within the native valve, displacing the calcified leaflets against the aortic wall rather than removing them.

Resident

The PARTNER 2A trial focused on intermediate-risk patients. How is this risk quantified in clinical practice, and how did the trial's primary endpoint results influence the management of a patient with an STS score of 5%?

Key Response

Surgical risk is quantified using the Society of Thoracic Surgeons (STS) Predicted Risk of Mortality (PROM) score; 'intermediate risk' is typically defined as a score between 4% and 8%. PARTNER 2A demonstrated that TAVR was noninferior to SAVR for the composite endpoint of all-cause mortality or disabling stroke at 2 years, providing high-level evidence that TAVR is a preferred or equal alternative to surgery for patients in this risk category.

Fellow

In the subgroup analysis of PARTNER 2A, why did the transfemoral access cohort show a potential superiority for TAVR, while the transthoracic access cohort did not, and what are the implications for procedural planning?

Key Response

In the transfemoral cohort, the TAVR group had a significantly lower rate of death or disabling stroke than the surgery group, whereas no such difference was seen in the transthoracic group. This suggests that the benefits of TAVR are maximized when performed via truly percutaneous, minimally invasive access. If a patient requires transthoracic (transapical or transaortic) access, the clinical advantage over traditional SAVR may be attenuated, making the decision more nuanced.

Attending

While PARTNER 2A established noninferiority at 2 years, how should the trial's findings regarding paravalvular leak (PVL) and its correlation with late mortality influence your long-term follow-up and counseling for a 68-year-old intermediate-risk patient?

Key Response

TAVR was associated with higher rates of paravalvular regurgitation than SAVR. Even mild PVL has been linked to increased long-term mortality. For a relatively young intermediate-risk patient (68 years), the potential for long-term valve-related complications and unknown durability beyond 5-10 years must be weighed against the immediate benefits of a less invasive procedure, necessitating longitudinal echocardiographic surveillance.

Scholarly Review

Critical appraisal through the lens of expert reviewers and guideline development

PhD

Evaluate the choice of the noninferiority margin (1.20 hazard ratio) in the PARTNER 2A trial. How does this margin affect the statistical power and the clinical interpretability of the findings when the upper bound of the 95% confidence interval is near the limit?

Key Response

The noninferiority margin of 1.20 means the study would accept TAVR being up to 20% worse than SAVR. In PARTNER 2A, the upper bound of the 95% CI for the hazard ratio was 1.17, which is very close to the 1.20 margin. While statistically 'noninferior,' this suggests that the results are sensitive to the chosen margin and that a slightly more conservative margin might have failed to reach significance, highlighting the importance of the margin selection in trial design for medical devices.

Journal Editor

The PARTNER 2A trial primarily utilized the SAPIEN XT valve, which has largely been replaced by the SAPIEN 3 and S3 Ultra. As an editor, how would you address the 'technological obsolescence' of the study device by the time of publication?

Key Response

This is a common issue in device trials. A critical appraisal would note that the SAPIEN XT lacked the outer skirt found on newer iterations (like the S3) designed to reduce paravalvular leak. An editor would flag that the trial's results likely represent a 'conservative' estimate of TAVR's benefit; if the older device is noninferior, the improved newer devices likely provide even better comparative outcomes, which supports the trial's relevance despite the device iteration change.

Guideline Committee

How did the results of PARTNER 2A specifically lead to changes in the 2020 ACC/AHA Guidelines for the Management of Patients With Valvular Heart Disease regarding the Class of Recommendation for TAVR in intermediate-risk patients?

Key Response

PARTNER 2A, along with the SURTAVI trial, provided Level A evidence that supported the transition of TAVR from a Class IIa to a Class I recommendation for symptomatic patients at intermediate surgical risk. Current guidelines (2020) now emphasize shared decision-making and patient age, recommending TAVR as a Class I option for patients aged 65-80 years who are at intermediate risk, effectively putting TAVR on equal footing with SAVR in this population.

Clinical Landscape

Noteworthy Related Trials

2010

PARTNER 1 Trial

n = 699 · NEJM

Tested

Transcatheter Aortic Valve Replacement (TAVR)

Population

Patients with severe aortic stenosis at high risk for surgery

Comparator

Surgical Aortic Valve Replacement (SAVR)

Endpoint

All-cause mortality

Key result: TAVR was noninferior to SAVR in patients with high surgical risk, establishing TAVR as a viable alternative.

2017

SURTAVI Trial

n = 1,746 · NEJM

Tested

Transcatheter Aortic Valve Replacement (TAVR)

Population

Patients with severe aortic stenosis at intermediate surgical risk

Comparator

Surgical Aortic Valve Replacement (SAVR)

Endpoint

All-cause mortality or disabling stroke at 24 months

Key result: TAVR was noninferior to SAVR for the primary endpoint in patients at intermediate surgical risk.

2019

PARTNER 3 Trial

n = 1,000 · NEJM

Tested

Transcatheter Aortic Valve Replacement (TAVR)

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 resulted in a significantly lower rate of the composite primary endpoint compared to surgery in low-risk patients.

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