Lotus Maintains Good Safety, Efficacy at 2 Years, Though Questions Persist Over Permanent Pacing

Two-year results of the REPRISE III trial show continued similarity regarding all-cause mortality as well as mortality and disabling stroke rates between the Lotus and CoreValve/Evolut TAVR devices. While the study authors believe the data are grounds for approval by the US Food and Drug Administration, others have concerns over issues like a higher pacemaker rate observed with the Lotus valve.

The 1-year findings, which were published last year, showed noninferiority of the mechanically-expandable Lotus valve (Boston Scientific) to the CoreValve first-generation and Evolut R valves (Medtronic) in terms of safety and hinted at an efficacy advantage, although the need for permanent pacemaker implantation was nearly double for Lotus over CoreValve.

To TCTMD, lead author Michael Reardon, MD (Houston Methodist DeBakey Heart and Vascular Center, TX), said he now expects the Lotus valve, which is unique in that it is designed to be fully recapturable and repositionable, to be approved by the FDA in the “near future.”

That prediction is in line with Boston Scientific’s: a company spokesperson told TCTMD earlier this year that it anticipates US approval in “mid-2019, pending regulatory approval timelines.”

The findings “give me great confidence in the Lotus valve,” Reardon said. “There are a lot of things that are pointing towards this being a really great third addition to the market. It's also still the only valve that can be fully deployed and then evaluated. Then if you like it you can release it, if you don't like it you can actually recapture it, remove it, change position.”

On the other hand, given that the pacemaker rate for Lotus rose to 41.7% at 2 years, Bina Ahmed, MD (Dartmouth-Hitchcock Medical Center, Lebanon, NH), told TCTMD that the manufacturer needs “to perhaps identify ways that they can reduce the incidence of the pacemaker complication and see if they can then better compete with the valves that are currently available.”

With the two transcatheter valves now on the market—CoreValve/Evolut and Sapien 3 (Edwards Lifesciences)—Ahmed said, “we pretty much can treat all patients that appropriately qualify for transcatheter aortic valve replacement. And so it's going to be a hard sell, especially with high pacemaker rates, for someone to consider a Lotus in exchange for CoreValve.”

Outcomes at 2 Years

The findings, published online this week in JAMA Cardiology, demonstrate that among the 912 patients enrolled in REPRISE III, rates of all-cause mortality as well as all-cause mortality or disabling stroke were comparable between Lotus and CoreValve at 2 years. While there was no difference observed with regard to overall stroke, disabling stroke was more frequent with CoreValve. Also, permanent pacemaker implantation and valve thrombosis rates (3.0% vs 0; P < 0.01) were higher in the Lotus valve cohort.

2-Year Outcomes

More patients in the CoreValve arm needed a repeat procedure (0.6% vs 2.9%; P < 0.01) or had a valve migration (0 vs 0.7%; P = 0.05) or embolization issue (0 vs 2.0%; P < 0.01). Additionally, valve areas remained larger and the gradient lower with CoreValve than with Lotus (P < 0.01 for both). Moderate or greater paravalvular leak was also more frequent with CoreValve at 2 years (0.3% vs 3.8%; P < 0.01).

Lastly, patients treated with the Lotus valve saw greater improvements in NYHA functional class at 2 years compared to those implanted with CoreValve.

An Attractive Third Option?

If the Lotus valve is approved for use in the United States, Reardon said he expects it will be an attractive option, especially for new TAVR centers as well as operators treating patients with severe calcium or other anatomies that may increase the risk of paravalvular leak. “The nice thing about it is that [each of] these valves work in three broad ways: balloon-expandable, self-expanding, or mechanically expanded. Now we'll have one valve in each of these categories,” he said.

“For those of us who are deeply involved in the field, having one more option is going to be good,” Reardon added. “It's good for our patients. It's good for the field.”

Ahmed highlighted that fact that patients in REPRISE III were at high and extreme surgical risk, “so these are pretty sick patients going in for valve replacement,” she said. “There's a real concern about shifting the transcatheter valve to lower-risk patients and having such high complication rates such as permanent pacemaker implantation rates or even concerns for valve thrombosis would make it hard for me to think about using this valve in our lower-risk patients.”

Also, given that the valve area seems to be smaller with the Lotus valve over time, Ahmed also raised concerns over durability with the new device. “If you were to continue following these patients, . . . you may see signs of recurrent stenosis, which could become relevant in the longer-term,” she said.

Where the Lotus valve may be useful is in “older patients that have a permanent pacemaker that's already implanted for other reasons,” Ahmed suggested, adding that it “does have the advantage of being repositionable, recapturable. It's brilliantly designed.”

The next step for the Lotus valve will be taken with the ongoing REPRISE IV study, which will include patients at intermediate surgical risk, Reardon said.

“All these valves are going to [probably] be applicable to 80% or more of the patients, that you just pick the valve you're comfortable using,” he concluded. “There's going to be 15-20% of the patients that may have anatomic criteria that may swing you toward one valve or the other, and I think by having this valve available for busy sites like mine that do a fair number every year, we now have one of each of the three different mechanisms of TAVR deployment available to us.”

Source: Boston Scientific