The New England Journal of Medicine June 09, 2011

Transcatheter versus Surgical Aortic-Valve Replacement in High-Risk Patients

Craig R. Smith, Martin B. Leon, Michael J. Mack, D. Craig Miller, Jeffrey W. Moses, Lars G. Svensson, E. Murat Tuzcu, John G. Webb, Gregory P. Fontana, Raj R. Makkar, et al.

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Bottom Line

In high-risk patients with severe aortic stenosis, transcatheter aortic-valve replacement (TAVR) was noninferior to surgical aortic-valve replacement (SAVR) regarding 1-year all-cause mortality, though the procedures presented different periprocedural risk profiles.

Key Findings

1. At 1 year, the primary endpoint of death from any cause occurred in 24.2% of the TAVR group and 26.8% of the SAVR group (an absolute reduction of 2.6 percentage points), meeting the predefined margin for noninferiority (P=0.001) but not superiority (P=0.44) [1.1].

2. At 30 days, the rates of death from any cause were 3.4% in the transcatheter group compared to 6.5% in the surgical group (P=0.07).

3. TAVR was associated with a higher rate of major strokes at 30 days (3.8% vs. 2.1%, P=0.20) and at 1 year (5.1% vs. 2.4%, P=0.07), while all neurologic events were significantly higher with TAVR at 1 year (8.3% vs. 4.3%, P=0.04).

4. Major vascular complications at 30 days were significantly more frequent with transcatheter replacement (11.0% vs. 3.2%, P<0.001).

5. Surgical replacement was associated with significantly higher 30-day rates of major bleeding (19.5% vs. 9.3%, P<0.001) and new-onset atrial fibrillation (16.0% vs. 8.6%, P<0.001).

6. At 1 year, moderate or severe paravalvular aortic regurgitation was significantly more common after TAVR than after surgery (6.8% vs. 1.9%, P<0.001).

Study Design

Design

Randomized Controlled Trial

Open-Label

Sample

699

Patients

Duration

1 yr

Median

Setting

Multicenter

Population High-risk patients with severe, symptomatic aortic stenosis who remained viable candidates for surgical replacement.

Intervention Transcatheter aortic-valve replacement (TAVR) using a balloon-expandable bovine pericardial valve via either a transfemoral or transapical approach.

Comparator Surgical aortic-valve replacement (SAVR).

Outcome Death from any cause at 1 year (assessed for noninferiority with a prespecified margin of 7.5 percentage points).

Study Limitations

• The trial was inherently unblinded due to the fundamental physical differences between open-heart surgery and a catheter-based intervention [1.4].

• The study utilized a first-generation balloon-expandable valve and large delivery sheaths, which directly contributed to the high rates of major vascular complications that are less prevalent with modern, lower-profile devices.

• The primary publication only reported 1-year follow-up, necessitating longer-term data to properly evaluate bioprosthetic valve durability and the late mortality implications of paravalvular leaks.

• The trial selectively enrolled elderly, high-risk patients with severe comorbidities, meaning these initial results could not immediately be generalized to intermediate or low-risk patient populations.

Clinical Significance

PARTNER 1A was a landmark trial that disrupted the traditional treatment algorithm for severe symptomatic aortic stenosis. By proving that TAVR provided equivalent 1-year survival to the gold-standard surgical approach in operable, high-risk patients, it established TAVR as a viable and less invasive clinical alternative. This catalyzed rapid iterations in transcatheter technology to address recognized complications—such as stroke and paravalvular leak—and provided the foundational evidence required to expand TAVR investigations into intermediate and low-risk populations.

Historical Context

Prior to the PARTNER trials, open-heart surgical aortic valve replacement (SAVR) was the only life-prolonging therapy available for severe symptomatic aortic stenosis, yet it carried prohibitive operative risks for many elderly or highly comorbid patients. The parallel PARTNER 1B cohort (published in 2010) established that TAVR drastically reduced mortality compared to standard medical therapy in patients deemed medically inoperable. PARTNER 1A (2011) represented the critical subsequent milestone, serving as the first large randomized trial to pit TAVR directly against surgery in operable but high-risk candidates, thereby initiating a modern paradigm shift in structural heart disease interventions.

Guided Discussion

High-yield insights from every perspective

Med Student

Medical Student

What are the classic symptoms of severe aortic stenosis, and why does the onset of these symptoms make interventions like those studied in PARTNER 1A urgently necessary?

Key Response

The classic symptoms of severe aortic stenosis are angina, syncope, and heart failure (dyspnea). Once these symptoms appear, the mortality rate increases dramatically, with survival averaging 2 to 5 years. This steep mortality curve is why mechanical intervention (SAVR or TAVR) is required, as medical therapy is ineffective.

Resident

In the PARTNER 1A trial, TAVR and SAVR had similar 1-year mortality but different peri-procedural complication profiles. Which specific complications were more frequent in the TAVR group versus the SAVR group, and how does this alter patient counseling?

Key Response

TAVR was associated with higher rates of major vascular complications and neurological events (strokes), whereas SAVR was associated with more major bleeding and new-onset atrial fibrillation. Counseling must be tailored to the patient's specific comorbidities, such as baseline stroke risk versus bleeding risk.

Fellow

Paravalvular aortic regurgitation (PVL) was more common after TAVR than SAVR in the PARTNER 1A trial. What are the pathophysiological consequences of moderate-to-severe PVL in a hypertrophied left ventricle, and how did this finding influence subsequent iterations of transcatheter valves?

Key Response

A non-compliant, hypertrophied left ventricle from chronic severe AS handles acute volume overload poorly, leading to elevated end-diastolic pressures and heart failure. Moderate-to-severe PVL was linked to increased late mortality, which drove the development of newer generation TAVR valves with external sealing skirts to minimize perivalvular leaks.

Attending

The PARTNER 1A trial formalized the 'Heart Team' approach for selecting patients for TAVR versus SAVR. From a practice-management perspective, how does this multidisciplinary model mitigate individual cognitive biases in assessing surgical risk and frailty?

Key Response

The Heart Team model requires consensus between interventional cardiologists, cardiac surgeons, and imaging specialists. This mitigates the bias of a single operator, ensures objective evaluation of frailty and anatomical feasibility, and optimizes shared decision-making for complex, high-risk patients.

Scholarly Review

Critical appraisal through the lens of expert reviewers and guideline development

PhD

PARTNER 1A utilized a non-inferiority design to compare TAVR to SAVR. Why is it critical to evaluate both intention-to-treat (ITT) and as-treated (per-protocol) analyses in a non-inferiority trial, and how do crossovers threaten the validity of the conclusions?

Key Response

In a superiority trial, ITT is conservative. However, in a non-inferiority trial, ITT can bias results toward the null (making treatments look similar), which increases the risk of falsely declaring non-inferiority (Type I error). Therefore, non-inferiority must be demonstrated in both ITT and per-protocol analyses to ensure robust, valid conclusions despite protocol deviations or crossovers.

Journal Editor

Because it is impossible to blind operators and patients to TAVR versus SAVR, how should editors critically appraise the reporting of subjective secondary endpoints like transient ischemic attacks (TIAs) or minor bleeding in this trial?

Key Response

Without blinding, performance and detection biases are significant risks. Editors must look for the use of an independent, blinded Clinical Events Committee (CEC) to adjudicate these outcomes using standardized definitions (like VARC criteria). Without a CEC, subjective endpoints might be heavily skewed by investigator bias.

Guideline Committee

Based on the PARTNER 1A findings, how did the AHA/ACC guidelines initially adapt their recommendations for high-risk patients with severe symptomatic aortic stenosis, and what specific clinical criteria distinguish a 'high-risk' SAVR candidate from an 'inoperable' one?

Key Response

Following PARTNER 1A, guidelines gave TAVR a Class I recommendation as an alternative to SAVR in high-risk patients. The distinction relies on the STS Predicted Risk of Mortality (PROM) score usually being >8% for high-risk, while 'inoperable' involves a >50% predicted risk of mortality or anatomical barriers like a porcelain aorta.

Clinical Landscape

Noteworthy Related Trials

2010

PARTNER 1B

n = 358 · NEJM

Tested

Transcatheter aortic-valve replacement (TAVR)

Population

Patients with severe aortic stenosis not suitable for surgery

Comparator

Standard therapy

Endpoint

Rate of death from any cause at 1 year

Key result: TAVR significantly reduced the rates of death from any cause and the composite end point of death or repeat hospitalization at 1 year compared to standard therapy.

2014

CoreValve US Pivotal High Risk Trial

n = 795 · NEJM

Tested

Self-expanding transcatheter aortic-valve bioprosthesis (CoreValve)

Population

Patients with severe aortic stenosis at increased surgical risk

Comparator

Surgical aortic-valve replacement (SAVR)

Endpoint

Rate of death from any cause at 1 year

Key result: TAVR with a self-expanding prosthesis was associated with a significantly higher rate of survival at 1 year compared to surgical replacement.

2016

PARTNER 2A

n = 2,032 · NEJM

Tested

Transcatheter aortic-valve replacement (SAPIEN XT)

Population

Patients with severe aortic stenosis at intermediate surgical risk

Comparator

Surgical aortic-valve replacement (SAVR)

Endpoint

Death from any cause or disabling stroke at 2 years

Key result: TAVR was noninferior to surgical aortic-valve replacement with respect to the primary end point of death or disabling stroke at 2 years.

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