乌鸦传媒

SAN FRANCISCO -- The Pascal device remained noninferior to MitraClip for prohibitive surgical risk patients with significant symptomatic degenerative mitral regurgitation (DMR) in full results from the pivotal CLASP IID trial.

For the primary safety endpoint, the 30-day composite risk of cardiovascular death, stroke, myocardial infarction, new need for renal replacement therapy, severe bleeding, and nonelective mitral valve reintervention was 4.6% with the Pascal versus 5.4% with MitraClip, which met noninferiority criteria, reported Firas Zahr, MD, of Oregon Health & Science University in Portland.

Noninferiority for the primary effectiveness endpoint of proportion of patients with mitral regurgitation no worse than 2+ at 6 months likewise persisted in the full cohort (97.9% vs 95.7%), he said at the Transcatheter Cardiovascular Therapeutics (TCT) meeting hosted by the Cardiovascular Research Foundation.

At 1 year, the two mitral transcatheter edge-to-edge repair (M-TEER) devices also remained similar for survival, freedom from heart failure hospitalization, and major adverse events (P>0.05 for all).

The findings, simultaneously published in , were similar to those presented from the interim analysis of 180 patients at TCT last year, which supported FDA approval.

"This report confirms the positive outcomes with the Pascal system in a larger cohort and extends key findings to 1 year," the researchers wrote.

Secondary endpoints also showed noninferiority in the trial. At 1 year, Pascal and MitraClip had similar rates of mitral regurgitation of up to grade 2+ (95.8% vs 93.8%) and of up to grade 1+ (77.1% vs 71.3%, respectively). Both device groups sustained similar, significant improvements in functional classification and quality of life from baseline (P<0.05 for all), with stable mean transmitral valve gradients at 1 year.

An by Jason Rogers, MD, of the University of California Davis, noted that this similarity eliminated the signal of differential efficacy raised by the interim analysis in terms of a higher percentage of mitral regurgitation grade 1+ with Pascal.

He called the similarities no surprise.

"The basic mechanism of edge-to-edge approximation of the anterior and posterior mitral leaflets is similar whether performed surgically or with a transcatheter device," he wrote. "With both the Pascal and MitraClip systems, the leaflets are captured simultaneously or individually and brought together by a miniature mechanical device to re-establish the zone of coaptation."

"This trial confirms the inherent strengths and weakness of the M-TEER approach in properly selected patients, which includes a high level of safety and also clinically meaningful but not complete MR [mitral regurgitation] elimination," he added.

The full trial cohort included a total of 300 adults with symptomatic, grade 3+ or 4+ DMR by transthoracic echocardiography (TEE) or echocardiography on core lab assessment who were enrolled at 54 U.S., Canadian, and European centers. They were at prohibitive surgical risk (largely due to frailty) and deemed eligible for either device by the local heart team. Participants were randomly assigned open-label 2:1 to Pascal or MitraClip.

A notable limitation was asymmetrical incomplete follow-up between groups, with 12-month transthoracic echo data in only 82.5% of eligible Pascal patients versus 93.2% in the MitraClip group. "This is a greater than 10% difference in follow-up rates between the two groups, which is quite large," Rogers noted.

Zahr and team wrote that "while these clinical results are encouraging, comparisons to other studies are challenging due to variations in study design, patient population, baseline degree of MR, device iterations, and echocardiographic assessments."

"Continued follow-up with more complete TTE assessments will be important and additional studies with larger patient populations or more complex valve pathologies might be needed to evaluate potential differences in the long-term durability of MR≤1+ results after M-TEER," they added.

Follow-up is planned to continue to 5 years.

There were four cases of single leaflet device attachments (SLDAs) with Pascal but none with MitraClip at 1 year, although the researchers noted that Pascal's rate was "low and comparable to contemporary MitraClip studies. Absence of SLDA in the MitraClip group may be explained by the greater operator experience with the MitraClip system."

Rogers pointed out that these events are "an important part of the safety profile of M-TEER devices" and could also be due to real differences in leaflet grasping mechanisms of the two systems or to patient-level factors.

Zahr and colleagues noted that most of the MitraClips used in the trial were the latest-generation G4 system (68.4%), but only about one in five Pascal devices were the newer-generation Precision system, and the Ace implant was available in the latter half of the enrollment period. "The fact that the outcomes in the CLASP IID trial were achieved with primarily the first-generation Pascal system is promising for the future of this therapy," they wrote.

TCT press conference moderator Roxana Mehran, MD, of the Icahn School of Medicine at Mount Sinai in New York City, called the outcomes "magnificent" for prohibitive-risk patients.

However, Yousif Ahmad, BMBS, PhD, of the Yale School of Medicine in New Haven, Connecticut, noted that a 20% rate of mitral regurgitation grade 1+ wouldn't be acceptable for mitral regurgitation valve surgery. "We do need to be a little cautious with the messaging," he said. "Mitral valve surgery for DMR is still the gold standard."

Robert Smith, MD, of Baylor Scott and White The Heart Hospital Plano in Texas, acknowledged that a surgical center of excellence would expect a mitral regurgitation 1+ rate of close to zero. However, that's not an option for inoperable patients, "so it doesn't matter," he said. "We're not really talking about the same group of people. When you don't have an option, this is an amazing therapy."

Smith presented CLASP IID registry data on 98 patients who received the Pascal device without randomization due to anatomy that made them not candidates for MitraClip, which showed sustained outcomes without significant changes during the additional 6 months of follow-up.

While it's not clear that there really are anatomic substrates better treated with one device versus the other, "competition is always good in any market," commented Wayne Batchelor, MD, of Inova Schar Heart and Vascular in Falls Church, Virginia, a panelist at the press conference.

In terms of picking one, Rogers said "practical factors such as device preparation (from unboxing to flushing the system), device steering (more degrees of freedom for catheter movement with Pascal but perhaps more stability with MitraClip), and overall familiarity and ease of use are equally important for adoption."