COMPARE-TAVI 1: Myval Performs Well Against Sapien at 1 Year

As legal battles continue between the manufacturers, the COMPARE-TAVI 1 trial has demonstrated that the Myval and Myval Octacor transcatheter heart valves (Meril Life Sciences) compare favorably with Sapien 3 devices (Edwards Lifesciences) in patients with severe aortic stenosis.

At 1 year, the rate of death, stroke, moderate/severe aortic regurgitation, or moderate/severe hemodynamic valve deterioration—the study’s primary composite endpoint—was 13% in Sapien-treated patients and 14% in Myval-treated patients, meeting the study’s noninferiority criteria.

Secondary or exploratory endpoints revealed some differences between the devices, however. Myval-treated patients required more new pacemaker implants and had higher rates of newly diagnosed atrial fibrillation (AF), moderate/severe aortic regurgitation, and bleeding related to the access site, but there were also indications of better hemodynamics versus Sapien 3 and Sapien 3 Ultra.

How those differences may influence longer-term results remains to be seen, Christian Terkelsen, MD, PhD (Aarhus University Hospital, Denmark), lead investigator of the study published online recently in the Lancet, told TCTMD.

“You can say that at 1 year, they are comparable,” he said. “Right now, we are convinced that you can safely use both valves.”

However, Ole De Backer, MD, PhD (Rigshospitalet, Copenhagen University Hospital, Denmark), who was not involved in the trial, expressed some reservations about Myval based on these results.

Though COMPARE-TAVI 1 was a “state of the art, well-conducted trial” that met its noninferiority endpoint, the outcomes beyond the primary endpoint show a clear difference in performance, he indicated. He expressed concerns about the increase in moderate/severe aortic regurgitation in the Myval arm between 30 days and 1 year and the higher rates of pacemaker implantation and bleeding.

“I do not think that the data in this comparative head-to-head TAVR trial is really encouraging to use Myval, to be honest,” he told TCTMD.

There is an ongoing legal dispute between the two device makers, which resulted in two pauses during enrollment in COMPARE-TAVI 1. Edwards sued Meril for infringing on one of its patents in Europe, and earlier this week, the Unified Patent Court ruled in favor of Edwards, according to legal reports. The court told Meril it had to stop selling its transcatheter heart valves running afoul of the patent, recall any on the market, and pay provisional damages. Other patent infringement cases continue, however.

The COMPARE-TAVI 1 Trial

Whenever a new transcatheter valve is developed, it should be compared with the best that are available, Terkelsen said, adding that price needs to be considered when deciding which one to use. “Sometimes new valves or those without evidence are launched at a low price, and it could be that they can compete,” he said. “But we shouldn’t use any valves in high volumes without also ensuring that we actually compare them with best in practice.”

COMPARE-TAVI 1, the largest randomized comparison of any two transcatheter heart valves, was conducted at three university hospitals in Denmark. Investigators enrolled 1,031 all-comer patients (median age 81.6 years; 40% women) who were scheduled for TAVI and eligible to receive any of the study valves. They were randomized to a Sapien valve—Sapien 3 (29 mm) or Sapien 3 Ultra (20, 23, or 26 mm)—or a Myval or Myval Octacor device (ranging in size from 20 to 32 mm). Most patients in the latter group (63%) received an Octacor.

At 30 days after the procedure, Sapien-treated patients had lower rates of first-time pacemaker implants (10% vs 19%) and moderate/severe aortic regurgitation (1% vs 2%) compared with Myval-treated patients. However, the Sapien group also had a smaller effective orifice area (EOA; 1.7 vs 1.9 cm²), a higher peak gradient (19 vs 16 mm Hg), and a higher mean gradient (11 vs 9 mm Hg).

The rate of moderate/severe patient-prosthesis mismatch at 30 days was greater with the Sapien valves (30% vs 19%), but VARC-3 type 2, 3, or 4 bleeding occurred less frequently (13% vs 22%; P < 0.0001 for both).

Myval devices proved noninferior to the Sapien devices for the primary composite endpoint, with the upper bound of the confidence interval around the between-group difference (4.4%) coming in below the prespecified margin of 5.3%. The findings in a per-protocol analysis were similar.

At 1 year, Myval devices were associated with higher rates of moderate/severe aortic regurgitation (4% vs 1%), first-time pacemaker implants (21% vs 12%), and newly diagnosed AF (14% vs 8%).

“The differences observed in individual components of the primary endpoint, as well as in secondary endpoints, might reflect the different technology on which the two balloon-expandable transcatheter heart valves are based,” the authors write in their paper.

“Follow-up will clarify whether differences in secondary outcomes affect prognosis, whether short-term differences in effective orifice area translate to differences in long-term durability, and whether these two balloon-expandable transcatheter heart valve series perform differently in those with small aortic valve annuli and in female patients,” they add.

Where Might Myval Fit In?

The higher rate of pacemaker implantation in the Myval group requires further study, Terkelsen et al say, suggesting that differences in device design and implantation techniques could be contributing factors. An ongoing CT substudy is exploring frame expansion, eccentricity, and implantation depth to provide some insights.

Terkelsen noted that the findings of COMPARE-TAVI 1 are largely consistent with those of the previously reported LANDMARK trial, which pitted Myval against contemporary valves from Edwards and Medtronic. Myval was noninferior to those at 30 days and provided a larger EOA compared with the Sapien devices. Terkelsen noted, however, that there are data indicating that a newer-generation Sapien 3 Ultra Resilia valve—which is being evaluated in COMPARE-TAVI 2—may provide a larger EOA.

As for whether Myval can find a place in practice alongside the more established device, Terkelsen pointed out that there is a wider range of sizes for Myval than with Sapien, for example. “In theory, there could be some benefit of more precise tailoring of the size.”

Myval is the only device with XL sizes, 30.5 and 32 mm, he said. “If you have a patient with a huge anatomy, this is actually the only valve you can use nowadays.”

Terkelsen added that other TAVI valves that haven’t fared as well when compared with best-in-practice devices are still on the market, whereas there is comparable performance with Myval. “Here you actually have a valve that can compete with both Evolut and Sapien, so why shouldn’t there be a place for this valve?”

Moreover, increased competition will likely drive down the cost of these devices and lead to further improvements in the technology, he indicated. “Truly, I think there’s room for new valves on the market if they can compete with Sapien and Evolut.”

De Backer agreed that having more valves on the market will be good in terms of pricing and advancements, but he balked at some of the Myval results. While acknowledging the better hemodynamics compared with the Sapien valves, he pointed out—as did Terkelsen—that the trial didn’t include the latest Sapien 3 Ultra Resilia valve, which is believed to have improved results.

Aside from the wider sizing choices, De Backer said the findings of COMPARE-TAVI 1 wouldn’t encourage him to shift his practice away from the more established Evolut and Sapien platforms.

Still, care should be taken when interpreting the results because they represent only 1 year of follow-up, De Backer said. More interesting is what happens over the longer term—up to 10 years or beyond—in terms of durability. Considering the mean age of patients in this trial, only about 20% will live that long, he estimated, so trials in younger patients undergoing TAVI are more likely to provide important insights over the longer term. That’s where the true value of head-to-head trials of these valves lies, he indicated.

Terkelsen agreed on the importance of following patients out for several years to see if early differences in hemodynamics between valves influence durability. He noted that 3-year follow-up from the first half of the COMPARE-TAVI 1 cohort will be presented at the upcoming EuroPCR meeting.