5-year Evolut Low Risk Data: Durable clinical outcomes, outstanding valve performance

Key findings of the five-year data

The Evolut Low-Risk Trial was a randomized, prospective multinational study designed to evaluate the performance of the Evolut TAVR system against surgery in patients with an STS-predicted risk of mortality score of 3% or lower. The primary endpoint of the study was all-cause mortality or disabling stroke. The trial also is looking at long-term durability of the TAVR valve compared to SAVR. 

Reardon reports that the primary endpoint at five years showed that the all-cause mortality and disabling stroke rates for TAVR remained numerically lower, yet statistically similar to those of surgery. However, an uptick in mortality was observed toward the later years of follow-up, prompting further analysis into its causes. 

Upon closer examination, Reardon divided the all-cause mortality data into cardiovascular and non-cardiovascular mortality. Cardiovascular mortality, directly related to effectiveness and durability of implanted valve, was numerically lower, but statistically similar (p value 0.15), however it widened from 1.1% difference at two years to 2.1% difference at five years.

"The delta in favor of Evolut was 1.1% at two years, and it's now 2.1% at five years,” he says. “So this very important metric of cardiovascular mortality is continuing to widen in favor of TAVR, gives us great confidence."

Conversely, non-cardiovascular mortality appeared to fluctuate due to external factors. In the latest year of follow-up, there were notable deaths due to malignancy, respiratory conditions, sepsis and COVID-19 in the TAVR cohort—which slightly altered the mortality trends. However, Reardon notes these events are considered random over time in a balanced patient population.

Hemodynamic performance and durability

One of the most crucial indicators of valve durability and effectiveness is hemodynamics, particularly mean gradient and effective orifice area (EOA). Reardon highlights that across all randomized trials, Evolut consistently demonstrated excellent hemodynamics compared to surgery, which could translate to long-term survival benefits.

"I'm a big believer in hemodynamics,” he explains. “The better you relieve aortic stenosis, the better you do. The closer I can get you back to normal, the longer you'll live.”

Hemodynamic changes over time are what ultimately lead to the gradual failure of a valve. In a separate analysis involving Reardon, researchers evaluated intermediate- and high-risk patients over a five-year period, using follow-up echocardiograms to track both gradual and more pronounced increases in transvalvular gradients—indicators of structural valve deterioration. The study specifically monitored increases in mean gradients of 10 mmHg or more with gradients exceeding 20 mmHg during the five-year follow-up period. In this analysis, five-year valve performance was significantly better after Corevalve Evolut TAVR compared to surgery and development of bioprosthetic valve dysfunction†, regardless of therapy was associated with an increased risk of mortality.²

Although the study emphasized gradient progression as an indicator of valve durability, Reardon points out that in general practice, low gradients also carry a concern for mortality, typically driven more by underlying cardiac dysfunction than by valve-related problems. "So if your gradient is half of what you think it should be, that's a problem,” he says. “It's probably low flow. If it's double what you think it can be, that's a problem because it's probably stenosis. And those are the things that we're parsing out with these trials.”

Recent analyses of bioprosthetic valve dysfunction† suggest that regardless of whether patients received TAVR or surgery, those who developed valve dysfunction experienced significantly higher mortality and rehospitalization rates.² Data from the NOTION-10 study with more than 4,700 patients further reinforced that the Evolut platform exhibited fewer cases of valve dysfunction compared to surgery in earlier years, though the statistical difference diminished by year 10.³

"If you look at the NOTION study, the original CoreValve, which was tested against surgery in patients who had a little higher STS risk score,” Reardon notes, “what we see is that for every year up to 10 years, the Evolut CoreValve had less bioprosthetic valve dysfunction than surgery.”

He also pointed to how SAVR valves are usually judged for durability and notes by that measure, Evolut is doing very well.

"Most surgical trials have really looked at reintervention as the main definition of durability,” he says. “And in this trial, there's no difference in the reintervention. So we'd say that TAVR, based on surgical criteria, is just as durable as surgery.”  

Pacemaker rates and paravalvular leaks 

Other measures of valve performance are managing the number of pacemakers that are needed after a valve replacement, and the level of paravalvular leak around the implanted valve. The trial has shown the need for more pacemakers with the Evolut than SAVR, as well has higher rates of paravalvular leaks. Reardon notes that operator experience has brought the pacemaker rate down to single digits.⁴ Even with the higher rates seen in low-risk trial, having a pacemaker within the first 30 days after TAVR did not impact patient mortality at five years.¹

The cusp overlap implantation technique has the potential to lower the risk of interaction with the conduction system by providing a more accurate assessment of THV depth. In the trial, the pacemaker rate was fairly high at about 20%. But Reardon points out that the trial was done from 2015 to 2019, before the standard use of the cusp overlap implantation technique to reduce the risk of interaction with the conduction system.

Paravalvular leak (PVL) also is higher in TAVR, but Reardon notes rates of moderate or greater PVL improved over time, and mild PVL at one month did not impact mortality at five years.¹

"So these things that we used to worry about that might cause increased mortality with Evolut versus surgery really have not panned out,” he concludes. “And I think it's based on the hemodynamics and the valve performance.”

Future implications for TAVR patient selection

Current U.S. guidelines⁵ recommend surgery for patients under 65 due to the lack of long-term data on TAVR durability. However, for patients aged 65 to 80, shared decision-making based on physiological and anatomical risk factors, as well as patient preference, is advised. Reardon emphasizes that for this population, the five-year results strongly support TAVR as a safe and effective alternative to surgery. 

Looking ahead, the ongoing evaluation of patients out to 10 years will provide further clarity on durability. “I am very interested in the 6, 7, 8, 9, and 10-year data,” Reardon says. “We will continue to push for annual reporting of these results for the safety of our patients and the advancement of our field.”