One-Year Data on Low-Risk TAVR Continue to Show Good Safety: LRT

WASHINGTON, DC—One-year data from an investigator-initiated study of TAVR in aortic stenosis patients at low surgical risk continues to show good safety, according to new findings from the LRT trial presented here.

The data come less than a month before the presentation of two pivotal trials at the American College of Cardiology (ACC) Scientific Session: the PARTNER 3 trial of the Sapien 3 valve (Edwards Lifesciences) and the Medtronic study of its Evolut R device, both comparing SAVR to TAVR in low-risk patients.

“Based on these [LRT] results, we can all be reassured that the randomized trials will meet their endpoint, and I think the next step will be to look at an approval for TAVR with the indication for low-risk patients,” said Ron Waksman, MD (MedStar Washington Hospital Center, Washington, DC), who presented the 1-year results today in a late-breaking clinical trial session at CRT 2019.

Thirty-day findings of LRT, which were released last year, showed no deaths or disabling strokes and a 4.8% rate of pacemaker implantation. Additionally, 6-year data from low-risk patients in the all-comers NOTION trial, presented last year at EuroPCR, demonstrated an edge with TAVR over surgery regarding hemodynamics and valve durability.

LRT Outcomes at 1 Year

LRT was an investigator-funded trial that followed 197 low-risk patients (STS score ≤ 3%) through 1 year post-TAVR. The majority received the balloon-expandable SAPIEN 3 device, while 11.8% were implanted with the Evolut R or Evolut PRO valve.

At 1 year there were six deaths (3.0%)—two from cardiovascular causes—four nondisabling strokes (2.1%), two MIs (1.0%), and no major vascular complications or life-threatening or major bleeding. Three additional patients reported new-onset A-fib between 30 days and 1-year, bringing the total to 6.3%, and one additional patient needed a pacemaker (7.3%). Overall, 6.8%, 2.1%, and 3.1% of patients were rehospitalized for cardiac, heart failure, and aortic-stenosis symptoms or procedure-related reasons, respectively, at 1 year.

Two patients reported endocarditis, which is “not that unusual” and can also be observed in SAVR cohorts, Waksman said. Also, one new patient had moderate or severe paravalvular regurgitation by 1 year (1.5%).

There were no durability issues demonstrated by the hemodynamic measurements taken between 30 days and 1 year, even among the 14.0% of patients who developed hypoattenuating leaflet thickening (HALT), 11.2% who were found to have reduced leaflet motion, and 7.4% who had hypoattenuation affecting motion (HAM). “I think that was encouraging because this is a signal that everybody is worried about. . . . Up to 1 year, it seems to be that it's very durable,” Waksman told TCTMD.

To gauge durability beyond 1 year, he said, “we will have to wait probably another 10 good years until we can compare [TAVR and SAVR] head-to-head.” In the meantime, Waksman said that if he needed TAVR and was at low surgical risk, he “would choose TAVR no doubt. I don’t want to wait 10 years for the data.”

In an additional analysis of subclinical leaflet thrombosis by antiplatelet/anticoagulant therapy, the 78.8% of patients only taking antiplatelet therapy reported more HALT than those on any oral anticoagulation (15.8% vs 7.7%). The ongoing LRT 2.0 trial will test whether routine anticoagulation after TAVR will prevent leaflet thrombosis, Waksman said.

Looking Forward to More Data

In discussion following the presentation of the LRT results, panelist Lars G. Svensson, MD, PhD (Cleveland Clinic, OH), noted that different TAVR studies use varying definitions of readmission (with some omitting the endpoint altogether).

“Rehospitalization is very tricky. When you go into the details of the study design of most of those trials, it’s very hard to understand [the endpoint],” Waksman replied, adding that the LRT researchers included all hospital readmissions but segmented out cardiovascular causes to highlight the relevant data. “I’m also curious to know how that’s going to appear in [the upcoming PARTNER 3 and Medtronic studies] and what will be exactly the definition of . . . rehospitalization,” he said.

For his part, panelist Michael Reardon, MD (Houston Methodist DeBakey Heart and Vascular Center, TX), who will be presenting the data from the Medtronic low-risk TAVR trial at ACC, commented that the mortality and stroke rates in LRT were on par with what has been seen in other published studies. “I’m glad to see that what you did confirmed that, with this group of patients, you can get excellent results and kudos to you,” he said.

Likewise, panelist Megan Coylewright, MD (Dartmouth-Hitchcock Medical Center, Lebanon, NH), asked Waksman specifically about the participating hospital sites in the LRT trial, given especially that endpoints like rehospitalization depend on the quality of the team-based care given. “The hospitals you recruited in this study were not necessarily the highest volume sites that we saw in prior trials,” she noted. “How do you think that impacted both your findings and how it might be applicable to broader scale distribution?”

I would like to be humble and modest, but the results are strikingly good. Ron Waksman

While Waksman’s institution, in his words, is “very experienced,” he confirmed that the 10 other participating centers had TAVR volumes ranging between 100-150 cases per year. “They were not good enough to be included in the randomized clinical trials. They have not participated before in any trial related to TAVR,” he said. “So we were struck by the excellent performance of those sites for this procedure. We didn't do any specific training. They chose the valve that they were comfortable with, but I have to tell you when we look at our performance versus their performance, there was really no difference.”

Panelist Howard Herrmann, MD (Penn Heart and Vascular Center, Philadelphia), asked about the implications of these findings on the long-term success of low-risk TAVR. “I think no one would be surprised if at ACC we find that TAVR is as good as surgery for these endpoints that are being studied in the two low-risk large trials in the short-term, 30-day, and 1-year outcomes,” he said. “What does it mean though to have small incidence of moderate [paravalvular leak (PVL)], a large incidence of mild PVL, a slightly higher pacemaker rate, maybe some strokes between 30 days and 1 year as we look at these patients over next 5 or 10 years?”

Waksman stressed that because LRT is not a randomized trial, several unanswered questions remain. But with all of the propensity matching and adjusting his team did to compare the TAVR results with a cohort from the Society of Thoracic Surgeons database, the pacemaker rates “were about the same” and there was no atrial fibrillation, he said. “I would like to be humble and modest, but the results are strikingly good. I don’t know how you can beat those results.”

That means, Waksman continued, we have “two good procedures that can be done. Surgery already has been proven to be good. I don't have to prove it to you. I’m presenting to you that TAVR with 200 patients can do also very well, not inferior to surgery. . . . To me, this is a deflecting point with respect to the expansion of the use of the technology. I'm willing to project that the studies that will be presented at ACC will corroborate this data, will reinforce it in a more rigorous way that this should be approved for expansion of labeling.”

Lastly, panelist Eberhard Grube, MD (University Hospital Bonn, Germany), asked for clarification on the age of the patients in this study, given that low-risk and young are not necessarily the same thing and that previous studies have put a lower limit on the age of patients eligible for enrollment. “Would you feel comfortable to say now we are ok with 70 years? Then what is the next breaking point? 65? Or do we have to do more trials to go even younger ages?” he asked.

“I’m comfortable with the age that was in the study, which was 71,” Waksman said. “Everything below 70 requires a good discussion between the patient and the heart team. We have been using bioprosthetic valves for 65 [years] in 95% of the surgical cases, so why should [TAVR] be different? [TAVR] should be treated the same way.”