Follow-up TAVR Studies Reassure About Valve Durability, Outcomes

SAN DIEGO, CA—In patients with severe symptomatic aortic stenosis at high surgical risk, TAVR provides durable hemodynamic results and at least comparable survival through 2 to 5 years compared with surgery, according to follow-up studies from the CoreValve US Pivotal Trial and the PARTNER trial presented March 15, 2015, at the American College of Cardiology (ACC)/i2 Scientific Session.

CoreValve Superior to Surgery

The main 1-year results from the high-risk cohort of the CoreValve (Medtronic) trial, which initially randomized 750 patients, were presented at ACC 2014 in Washington, DC. TAVR reduced mortality compared with surgery (14.2% vs 19.1%; P = .04 for superiority), with an absolute survival advantage of 4.8%.

Michael J. Reardon, MD, of Houston Methodist Hospital (Houston, TX), presented the 2-year results—the absolute survival advantage for TAVR grew to 6.5% compared with surgery (22.2% vs 28.6%; P = .04) with a consistent benefit across subgroups.

A similar pattern was observed for the rate of any stroke, which favored TAVR by an absolute 3.8% at 1 year. By 2 years, the advantage was 5.7% (10.9% vs 16.6%; P = .05). There was a numerically lower rate of major stroke in the CoreValve group at 2 years (6.8% vs 9.8%; P = .25).

The rates of MACCE and of the composite of all-cause mortality or major stroke remained lower in the TAVR group at 2 years, with a widening of the gap between groups.

In terms of other outcomes, CoreValve continued to be associated with higher rates of major vascular complications (7.1% vs 2.0%; P = .001), pacemaker implantation (25.8% vs 12.8%; P < .001), and reintervention (2.5% vs 0.4%; P = .02). Surgery, on the other hand, continued to carry elevated risks of life-threatening or disabling bleeding (39.6% vs 18.1%), new-onset or worsening A-fib (34.9% vs 19.5%), and acute kidney injury (15.1% vs 6.2%; P < .001 for all).

There were no differences between groups in valve endocarditis, valve thrombosis, or embolization.

Echocardiography demonstrated consistently better valve performance in terms of aortic valve area and mean gradient at each time point through 2 years, with no evidence of structural valve deterioration in either the TAVR or surgery groups. Although paravalvular regurgitation remained lower with surgery, moderate-to-severe regurgitation was infrequent with TAVR (6.5%).

The bottom line, Dr. Reardon said, is that the findings support a change to the AHA/ACC guidelines, which say that TAVR is a reasonable alternative to surgery among patients at high surgical risk.

These findings “would suggest that TAVR with the self-expanding CoreValve system is not just a reasonable alternative but is really the preferred [option] in this patient group,” he said.

First-Generation Sapien Valve Shows Long-Term Durability

Michael J. Mack, MD, of Baylor Scott & White Health (Plano, TX), reported the 5-year results from Cohort A of the PARTNER trial, which were published simultaneously in The Lancet. The primary 1-year results demonstrated that survival following TAVR with the Sapien valve (Edwards Lifesciences) was noninferior to that achieved with surgery, although stroke was more common following TAVR.

Consistent with previous follow-up studies, the risk of death remained statistically similar in the 2 study arms through 5 years—67.8% with TAVR and 62.4% with surgery (HR 1.04; 95% CI 0.86-1.24). Median survival was 44.5 and 40.6 months in the TAVR and surgery groups, respectively (P = .76).

There were no between-group differences in mortality in either the patients suited for the transfemoral approach or the transapical approach, but there was a trend toward higher mortality following TAVR vs surgery in the latter group (79% vs 60%; P = .067).

After converging at around 2.5 years, the risk of stroke/TIA was similar in the 2 groups through 5 years. There also were no differences in rates of repeat hospitalization, MI, endocarditis, renal failure, or new pacemaker implantation, or in the proportion of patients in NYHA class I or II. Vascular complications were more common and bleeding was less frequent in the TAVR group with most cases of both occurring shortly after treatment.

Echocardiography showed that valve hemodynamics remained similar in both groups, and there were no cases of structural valve deterioration requiring surgical valve replacement in either group.

Moderate-to-severe aortic regurgitation was higher with TAVR, and this—as well as mild regurgitation—was associated with a greater risk of death during follow-up.

Substantial progress has been made in addressing the regurgitation problem since the PARTNER trial began, according to Dr. Mack, who said newer-generation devices are better, investigators are more experienced, and imaging is now used to better size valves.

“This trial was the first study of this first-generation device in most clinical study centers,” the study authors write. “Present devices are second- and third-generation, with smaller delivery systems and designed to prevent paravalvular leak. Thus, outcomes of TAVR are likely to be better in current clinical practice. In addition, many more years of clinical experience leading to better patient selection and surmounting early learning curves probably further contribute to better outcomes.”

Durability Question Remains Unanswered

Panelist Jeffrey J. Popma, MD, of Beth Israel Deaconess Hospital (Boston, MA), asked whether the durability of transcatheter valves now equals that of surgical valves.

Dr. Mack said that the findings through 5 years are reassuring, but “I don’t think we’re far enough out to totally be able to put [the issue] to bed.” He noted that the echo findings are only from survivors and that patients with patient-prosthesis mismatch were not likely to survive to 5 years.

At a press briefing, Dr. Popma said that TAVR shows durability in high-risk patients. “Five years ago we weren’t quite sure how it was going to go late,” he said. “We’ve seen no safety signals. We’ve seen no valve deterioration that would be worrisome. So the clinical decision the public is making about using transcatheter valves in lieu of surgery in high-risk patients has held up.”

Findings Challenge Dominant Position of Surgery

In an editorial accompanying the PARTNER paper, A. Pieter Kappetein, MD, PhD, of Erasmus University Medical Center (Rotterdam, the Netherlands), says “the findings challenge whether surgery can still be considered the gold standard for patients at high surgical risk.”

He points out that in 2008, Dr. Mack “predicted that the benefits of new, less invasive procedures for percutaneous heart valve treatment would equal or surpass those of their open-surgery predecessors, and concluded that patients will choose a less invasive approach over a more invasive one even if there is uncertainty. With more than 150,000 implantations worldwide and the indication shifting towards intermediate-risk patients, this prediction has been met.”

Dr. Kappetein agrees that the findings were reassuring as to the durability of TAVR with the Sapien valve. “This study is the first to report similar outcomes at 5 years from prospectively collected echocardiographic data analyzed at an independent core laboratory, an important stage in determining whether durability matches that of surgical bioprostheses.”

Taking into account the 5-year results and the possibility that outcomes will be improved with newer-generation devices, “one can conclude that—in a selected cohort of high-risk patients—the clinical results of TAVR equal those of [surgery],” he continues, adding that “such patients will undoubtedly opt for the less invasive approach.”

 

 

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Sources:1. Reardon MJ. CoreValve US Pivotal Trial: a randomized comparison of self-expanding transcatheter and surgical aortic valve replacement in patients with severe aortic stenosis deemed at increased risk for surgery 2-year outcomes. Presented at: American College of Cardiology/i2 Scientific Session; March 15, 2015; San Diego, CA.

 

 

2. Mack MJ, Leon MB, Smith CR, et al. 5-year outcomes of transcatheter aortic valve replacement or surgical aortic valve replacement for high surgical risk patients with aortic stenosis (PARTNER 1): a randomized controlled trial. Lancet. 2015;Epub ahead of print.

Disclosures:

 

• The CoreValve US Pivotal Trial was funded by Medtronic.
• The PARTNER trial was funded by Edwards Lifesciences.
• Dr. Reardon reports serving on the medical advisory board for Medtronic.
• Dr. Mack reports receiving travel reimbursements from Edwards Lifesciences relating to his position as an unpaid member of the PARTNER trial executive committee.
• Dr. Kappetein reports serving on the steering committee for the SURTAVI trial.
• Dr. Popma reports receiving consulting fees/honoraria from Abbott, Abbott Vascular, Abiomed, Boston Scientific, and Cordis and research grants from Abbott, Abbott Vascular, Abiomed, Boston Scientific, Cordis, eV3, and Medtronic.

 

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