San Francisco — In the first randomized controlled trial using the TriClip Transcatheter Tricuspid Valve Repair system (Abbott) for transcatheter edge-to-edge repair (TEER) of the tricuspid valve in patients with severe tricuspid regurgitation (TR), patients showed sustained TR reduction and improvements in quality of life at 1 year as well as safety at 30 days.
The trial also involved a single-arm nonrandomized group who was unlikely to achieve moderate or less TR; all were treated with TriClip.
"Data from all randomized subjects analyzed to date in the TRILUMINATE Pivotal trial strengthens our previously reported findings from the primary cohort analysis," David Adams, MD, of Mount Sinai in New York, told attendees at the Transcatheter Cardiovascular Therapeutics 2023 congress.
Those results were presented earlier this year at the American College of Cardiology/World Congress of Cardiology joint scientific session, reported by theheart.org | Medscape Cardiology at that time.
Outcomes between the randomized and single-arm cohorts were comparable in terms of procedural safety, sustained TR reduction, and positive changes in 12-month Kansas City Cardiomyopathy Questionnaire (KCCQ) scores, he said.
The two arms of the study were based in part on expected TR reduction. The randomized arm enrolled patients expected to achieve TR improvement of moderate or less, randomly assigning them 1:1 to the TriClip device or to medical therapy alone. The single-arm group consisted of patients expected to achieve a TR reduction of at least one grade but not to moderate or less, and they were all treated with the TriClip device.
Patients were included if they had severe symptomatic TR, had stable guideline-directed medical and/or device therapy for heart failure for 30 days or more, and were at least at intermediate risk for morbidity or mortality from tricuspid valve surgery. Among exclusion criteria were an indication for another valve disease intervention, severe pulmonary hypertension, left ventricular ejection fraction of 20% or less, and anatomy for which the TriClip device is not compatable.
The primary endpoint for the randomized part of the trial was a hierarchical composite of all-cause mortality or tricuspid valve surgery, heart failure hospitalization, and KCCQ improvement ≥ 15 points at 12 months.
This part of the trial enrolled 589 patients, of whom, 572 were treated. Mean age was 78.1 years ± 7.8 years, 59% were women, and 55% were in New York Heart Association Class III or IV. TR severity was severe, massive, or torrential in 98%.
Improvements in QOL, but Mortality Remained
Among all randomized patients (N = 572), TriClip TEER substantially reduced TR severity. At baseline, 98% of patients had severe or greater TR, which was reduced to moderate or less in 88% of all randomized patients at 12 months. For control patients, 99% had severe or greater TR at baseline, as did 94% at 12 months.
However, mortality was no different between the device group and control group: 90.1% vs 90.3%, respectively, at 12 months. The heart failure hospitalization rate at 12 months was only slightly better for the device group, at 17% vs 19% for control group.
Almost twice as many in the device group (50%) had better quality of life as indicated by an improvement of KCCQ overall summary scores ≥ 15 points compared with control group (26%) at 12 months.
Judged by the primary endpoint for all randomized patients, the device group was 53% more likely to have a better outcome. "Win" comparisons, a way of analyzing composite endpoints to account for the hierarchy of clinical significance of their components and to include recurrent events, showed calculated 24,205 wins for the TriClip recipients vs 15,783 for control participants (win ratio, 1.53; 95% CI, 1.14-2.05; P = .0042).
The 6-minute walk test at 12 months, which was not part of the primary endpoint, also showed significant benefits in a paired analysis of the device group compared with the control group (+15 meters vs -12 meters; P = .01).
In the single-arm part of the TRILUMINATE Pivotal trial, all patients (N = 100) received a TriClip device only. The primary endpoint for this cohort was survival through 12 months with KCCQ improvements ≥ 10 points compared with baseline. These were patients unlikely to achieve moderate or less TR but deemed to be able to have TR reduced by one grade.
They were slightly older (age 80.4 years) than the randomized group was (age 78.1 years), had a significantly greater presence of cardiac leads (35% vs 16%) and prior aortic or mitral intervention (44% vs 36%), as well as a greater proportion of torrential TR (all P < .05).
There were no differences between the single-arm and all randomized TEER recipients (N = 281) in terms of procedural outcomes, including in-hospital mortality (0% for each).
The outcomes for the single-arm group compared favorably with the randomized controlled trial group who received the TriClip device despite the more complex anatomies and therefore higher risk in the single-arm group.
Whereas at baseline all or almost all participants in each group had severe, massive, or torrential TR at 12 months, 81% in the single-arm group had moderate or less TR vs 89% with moderate or less TR in the randomized group. Thirty-day outcomes were very similar to 12-month outcomes for each group.
Similarly, KCCQ quality of life overall scores improved in parallel for the two groups. At 1 month, the scores for each group had improved by approximately 15 points from baseline, and at 12 months the improvements in scores were 14.5 ± 20.0 for the single-arm group and 15.2 ± 22.3 for the randomized-device group. The single-arm group reached its primary endpoint of survival at 12 months with at least a 10-point improvement in quality-of-life KCCQ scores over baseline.
There were very few major adverse events through 30 days in the single-arm cohort. The only ones that occurred were tricuspid valve reintervention (2%), major bleeding (5%), tricuspid mean gradient ≥ 5 mm Hg (3%), and single-leaflet device attachment (7.5%).
However, given the initial higher risk status of the single-arm patients at the outset, their 12-month all-cause mortality was higher than for the randomized group (15.0% vs 8.6%) as was hospitalization for heart failure (24.0% vs 14.9%).
After Adams' presentation, Gorav Ailawadi, MD, of University of Michigan Health, began the discussion, noting that TRILUMINATE is the first randomized trial of tricuspid transcatheter valve repair.
Referring to the first publication of the original 100 nonrandomized patients, he said, "Kudos to you for continuing to follow these patients and adding to the cohort…And now you've been able to show what we didn't see in the first go around, an actual improvement in the 6-minute walk, which is, I think, an important thing to add."
He emphasized the fact that it was a very sick population, at almost 80-years-old, many women, "with many, many comorbidities."
Adams responded that he thinks the expectations for patients like these ones, who have severe tricuspid regurgitation and who are older and have had their left-sided valve treated needs rethinking.
"When I've talked to patients previously about having tricuspid valve surgery, I don't remember ever telling them they'll come to the hospital less often after a surgery," he said. "I told them, they'll feel better. I'm assuming their medical management will be easier...It's been a readjustment for us to sort of think about quality of life."
Ailawadi then asked whether there is now sufficient evidence to consider TriClip repair for such sicker patients with more complicated tricuspid anatomy despite no control arm of medical therapy for these patients in the single-arm component of the trial.
"I'm hoping that one day we will have a portfolio of ways to do repair and replacement of the tricuspid valve in these patients," Adams said, adding that the potential pool of candidates for TriClip therapy "has expanded based on the data I've shown you today."
Philipp Lurz, MD, PhD, leads a large tricuspid therapy program at the University of Leipzig, Germany, and offered his thoughts, calling the results of the single-arm group "incredibly important." He said that the most striking result for him was their 15% mortality: "so much higher than in the randomized cohort."
Although they had "completely different risk at a first glance, the baseline characteristics aren't that different," he pointed out. "So that once again shows how heterogeneous TR is," and "how limited we still are in predicting the risk of these patients."
In his opinion, the single-arm cohort may be the best cohort for a randomized trial. "So, although [that group was] not randomized, I think it's really, really important that [that] will be instrumental for the design of the next generation trials," Lurz said.
Adams agreed, and in hindsight said, "If we had known what we know today, when we designed this trial, we would have randomized all those patients."
The TriClip device is available only for investigational use in the United States.
The trial was sponsored by Abbott. Mount Sinai receives royalties from Edwards Lifesciences and Medtronic related to Adams' intellectual property rights in valve repair rings. Adams has received grant support/research contract from Medtronic, NeoChord, and Abbott. Ailawadi has received consultant fees/honoraria or is on the speaker's bureau of Abbott, Medtronic, Edwards Lifesciences, W.L. Gore & Associates, Philips, JenaValve, Anteris, Atricure, CryoLife, Johnson & Johnson, and Arthrex. Lurz was on the Anatomic Eligibility Committee of the study and has received honoraria from Innoventric.
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