TriClip’s ‘Soft’ Benefits Affirmed in Severe Tricuspid Regurgitation

LONDON — Tricuspid transcatheter edge-to-edge repair (T-TEER) improved how well patients functioned and felt without major cardiovascular events in the first academic randomized trial to affirm the pivotal trial findings.

T-TEER with the TriClip device improved a clinical composite score of change in New York Heart Association (NYHA) class, patient global assessment, and no cardiovascular hospitalization or death at 12 months, reported Erwan Donal, MD, PhD, of University Hospital Pontchaillou in Rennes, France, at the European Society of Cardiology (ESC) meeting.

The proportion of patients who improved was 74.1% after T-TEER and 40.6% on guideline-directed medical therapy alone, with a 0.67 probability of a better rank on the range from worsened to improved score at 12 months after the procedure (P

These findings were “in line with” the TRILUMINATE pivotal trial that led to FDA approval of the TriClip, Donal said. It had shown a Bayesian win ratio of 1.48 (P=0.02) for the hierarchical composite of death from any cause or tricuspid-valve surgery, hospitalization for heart failure, and improvement in quality of life at 1 year. The difference was driven by quality of life.

For the same composite, Donal and colleagues’ Tri.Fr trial showed a win ratio of 2.06 (95% CI 1.38-3.08). And unlike in TRILUMINATE, all the parameters favored TriClip at least numerically.

Donal called the results in terms of reducing the impact of tricuspid regurgitation (TR) on patients’ daily lives “highly encouraging.”

“We clearly showed the benefits of T-TEER, as seen in the TRILUMINATE trial, but using T-TEER as part of a global approach and treating heart failure with guideline-directed medical management and follow-up,” he said in a statement. “A key message of the Tri.Fr trial is that implementing rigorous multidisciplinary medical management resulted in a low event rate, even in very ill patients with secondary TR. Using T-TEER with optimal medical management also led to important quality-of-life improvements. It remains to be seen if patients with a particular phenotype of severe TR derive more benefit from T-TEER than others.”

However, ESC session study discussant Frank Ruschitzka, MD, of the University Hospital in Zurich, was critical of the lack of evidence of survival or hospitalization benefits in an open-label trial and for the procedure overall across trials.

“It cannot be a blinded procedure, so be careful and humble to overplay anything on a soft endpoint,” he argued. “And to that point, even heart failure hospitalization may be subject to bias. And I’m talking about performance bias here, so we should be humble. There is no difference. That is, for me, meaningful. In the heart-failure world, when we talk about pillars, pillars means mortality reduction proven. We are far from that here.”

TriClip is not available commercially in France, so no crossover has occurred, Donal noted. “So we have a long-term follow-up at 2 and 5 years … so maybe we might have the opportunity within the next year to provide you hard endpoints.”

Tri.Fr trial included 300 patients at 24 centers in France and Belgium who had symptomatic (NYHA functional class II to IV), severe secondary tricuspid regurgitation despite medical management, who were stable for at least 30 days, and who were not candidates for surgical correction. They were randomized to receive either T-TEER plus guideline-directed medical treatment or optimal medical treatment alone.

The patient population had a mean age of 78, and 64% were women. Among them, 40% had been hospitalized for heart failure within the year prior to entering the trial, and 15% had a cardiac implantable electronic device.

The primary composite endpoint was considered improved if the patient survived without cardiovascular hospitalization and had a favorable change in NYHA or the patient global assessment was mildly to markedly improved.

Among the secondary endpoints, the probability of improvement in core lab-assessed tricuspid regurgitation grade was 0.73 (95% CI 0.68-0.78, PP

Notably, nearly 97% of T-TEER patients survived and 84% did so without a cardiovascular hospitalization at 1 year. While the trial was not designed to detect statistically significant differences in these outcomes, Donal pointed out that “under a strict medical follow-up, the event rate has been, at 1 year, much lower than in previous registries and TRILUMINATE pivotal trial.”

He also argued that “you have to keep in mind that 121 patients have been hospitalized in the 12 months before randomization and only 35 of them have been hospitalized at 1 year follow-up with a 1 year mortality of 3.4%.”

Ruschitzka criticized the low use of sodium-glucose cotransporter 2 (SGLT2) inhibitors and mineralocorticoid receptor antagonists in the study population, at just 16% and 70% in the T-TEER group and 23% and 80% in the control group, respectively.

“We love drugs and devices and interventions in heart failure,” he said. But similar to the story in cardiac resynchronization therapy where deep phenotyping has been key to success, “we define a sweet spot, and we have to team up. It’s not an ‘either/or.’ It’s working together.”