PARTNER: In High-Risk Surgical Candidates, TAVI Proves Just as Effective

NEW ORLEANS, LA—Transcatheter aortic valve implantation (TAVI) matches surgical valve repair at 1 year, with similar mortality rates in high-risk patients with aortic stenosis considered eligible for either procedure. The much anticipated results, presented in a late-breaking clinical trial session at the American College of Cardiology Scientific Session/i2 Summit on April 3, 2011, suggest that TAVI may be suitable for a wider patient population than previously shown, but worries remain about stroke rates.

Previous findings from the PARTNER (Placement of AoRTic traNscatheterER valves) trial, published in the New England Journal of Medicine last October, focused on a group of patients who were not suitable candidates for surgery, known as cohort B. TAVI performed with the Edwards Sapien aortic valve system (Edwards Lifesciences, Irvine, CA) significantly reduced all-cause death, all-cause death/repeat hospitalization, and cardiac symptoms but led to increased rates of major stroke and major vascular events compared with standard therapy.

Testing TAVI vs. Surgery

In the latest update to PARTNER, Craig R. Smith, MD, of Columbia University Medical Center (New York, NY), shared details from the trial's cohort A, which enrolled 699 high-risk, operable patients at 26 centers whose median age was 84.1 years. The patients, all of whom had symptomatic, severe aortic stenosis, were randomized to undergo either surgery (n = 350) or TAVI (n = 348). Among the TAVI group, 244 subjects received treatment using transfemoral access and 104 the using transapical route. Baseline characteristics were largely similar across the 2 treatment groups, although TAVI patients treated transapically had a higher risk profile.

At 30 days, all-cause death was less common with TAVI than surgery, but by 1 year, mortality (primary endpoint) was equivalent between the 2 treatments. Major strokes, however, were higher for TAVI patients for both follow-up durations; the difference reached significance when considering the composite of stroke/transient ischemic attack (TIA). Though major vascular complications were increased with TAVI, this difference was balanced by decreases in major bleeding and new onset atrial fibrillation (table 1).

Table 1. Clinical Outcomes at 1 Year

^a Primary endpoint; P = 0.001 for noninferiority.

Looking separately at the 2 TAVI approaches, transfemoral access produced similar levels of all-cause death at 1 year compared with surgery (P = 0.002 for noninferiority). Although the transapical cohort was too small to make an adequate comparison, it also appeared to match surgery for the primary endpoint.

In all, 42 patients did not undergo their assigned treatment: 1.1% in the TAVI arm and 10.8% in the surgical arm. Yet a per protocol analysis found that the major endpoints did not differ substantially from the main intent-to-treat analysis.

Both surgery and TAVI improved New York Heart Association functional class and 6-minute walk test results, with TAVI holding the advantage at 30 days but not at 6 months or 1 year. In addition, “[s]ubgroup analyses suggest that females and patients without prior coronary bypass might better benefit” from TAVI, Dr. Smith noted.

Among the limitations of the study are that it assessed an early version of the TAVI technology and most sites (19 of 26) had no previous experience with the procedure, he said. Moreover, the trial's follow-up duration was too short to fully assess the new treatment's durability.

Not only did the trial meet its primary endpoint, Dr. Smith stressed, but the 30-day death rates were lower than expected in both arms of the trial. Overall, TAVI and surgical repair “are both acceptable therapies in these high-risk patients. Different periprocedural hazards may impact case-based decision-making,” he said, adding that TAVI is now “an acceptable alternative” to surgery in selected high-risk operable patients and should be tested in randomized trials of lower risk patients.

Stroke Risk Shrinks But Still Concerns

Following Dr. Smith's presentation, session co-chair David J. Moliterno, MD, of the University of Kentucky (Lexington, KY), drew attention to differences in cohort A and cohort B. “Even between these 2 studies, we see a 20 to 30% reduction in mortality and stroke” within the TAVI group, he said, asking why outcomes might have changed.

“It's hard to isolate 1 reason why it improved,” Dr. Smith replied. “Experience, time, glacial things that occur with any new procedure. You might expect that the inoperable patients were sicker, because they were inoperable. If so, it doesn't emerge in the [Society of Thoracic Surgeons] risk score. It's a reasonable presumption, though.”

Robert O. Bonow, MD, of the Northwestern University Feinberg School of Medicine (Chicago, IL), said he was struck by how the PARTNER results will affect clinical decision making. “We need to develop a case based approach for individual patients and have a very careful discussion with our patients about the early procedural risks related to bleeding and atrial fibrillation with surgery and stroke with the transcatheter approach,” he noted, questioning whether stroke is the outcome to be weighed most heavily.

Experience, smaller devices, and the use of embolic protection will likely reduce the stroke risk further, Dr. Smith commented. “On the other hand, stroke will be focused upon. It is, in many people's minds, a worse outcome than death,” he said, pointing out that the rate was doubled by TAVI vs. surgery, even though it did not reach statistical significance. “It will require attention. The way I look at it, this is a much lower neurological event rate than any of us imagined was possible 10 years ago.”

Source:

Smith CR. Transcatheter aortic valve implantation versus surgical aortic valve replacement in “high risk” patients with aortic stenosis: The randomized PARTNER trial. Presented at: American College of Cardiology Annual Scientific Session/i2 Summit; April 3, 2011; New Orleans, LA.

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