Edwards Lifesciences Highlights PASCAL, TAVR Data Showing Patient Benefits

Key Points

• PASCAL’s CLASP IITR trial met its six-month primary endpoint, with treated patients nearly twice as likely to benefit as those receiving medical therapy alone. Benefits were driven mainly by improved quality of life, while 80% of PASCAL patients had moderate or less tricuspid regurgitation at one year versus 30% of controls.
• The PROGRESS trial found TAVR benefited selected patients with moderate aortic stenosis. TAVR reduced the two-year risk of death or heart-failure events by 33%, primarily through a 52% reduction in heart-failure hospitalizations, with a number needed to treat of 14.
• The findings could broaden how clinicians assess and manage moderate aortic stenosis, but TAVR is not currently approved for this indication. Edwards said the trial was designed with the FDA, without providing a timeline for potential label expansion.

Edwards Lifesciences NYSE: EW highlighted new clinical data for its transcatheter tricuspid repair and transcatheter aortic valve replacement programs, including results from the CLASP IITR trial of the PASCAL system and the PROGRESS trial evaluating TAVR in certain patients with moderate aortic stenosis.

CLASP IITR meets six-month primary endpoint

Charlie Davidson, chief of cardiology and medical director of the Bluhm Cardiovascular Institute and global co-principal investigator of CLASP IITR, said the trial met its six-month composite primary endpoint. The study compared the PASCAL transcatheter edge-to-edge repair system plus optimal medical therapy with optimal medical therapy alone in symptomatic patients with severe or greater tricuspid regurgitation.

The composite endpoint included mortality, right ventricular assist device implantation or heart transplant, tricuspid valve intervention, heart-failure hospitalizations and improvement in Kansas City Cardiomyopathy Questionnaire, or KCCQ, scores. Davidson said the trial produced a win ratio of 1.98, meaning patients receiving the device were approximately twice as likely to experience benefit versus those receiving medical therapy alone.

The primary endpoint was largely driven by health-status improvement as measured by KCCQ scores. Davidson said 57% of device-treated patients achieved a moderate-to-large improvement, while 25% of patients in the control group worsened. He noted that the medical-therapy regimen included SGLT2 inhibitors, which had not been routinely used in some prior tricuspid trials.

There was no statistically significant difference in mortality or heart-failure hospitalizations between study groups at six months. Davidson said the study was not designed to determine a mortality difference over that time frame. He also cited a 4% mortality rate in the control group and patient attrition after competing tricuspid devices received regulatory approvals.

At one year, 80% of patients treated with PASCAL achieved moderate or less tricuspid regurgitation, compared with 30% of the control group, according to Davidson. He said patient-reported health-status gains were evident by 30 days and persisted through one year.

Davidson also discussed the previously presented TRIC-I-HF study, which enrolled tricuspid-regurgitation patients with features including cardiorenal impairment, hepatorenal dysfunction or prior heart-failure hospitalization. He said the trial showed differences in death and heart-failure hospitalizations, while longer follow-up could provide additional evidence on mortality.

Looking forward, Davidson said important questions include identifying which patients should be treated and when intervention should occur. He also said tricuspid regurgitation remains underdiagnosed, including in general cardiology and echocardiography settings.

PROGRESS evaluates TAVR in moderate aortic stenosis

Philippe Généreux, co-director of the Structural Heart Program at Morristown Medical Center, presented the PROGRESS trial, which compared a TAVR strategy with clinical surveillance in patients with moderate aortic stenosis and at least one feature associated with greater risk of heart failure or more rapid disease progression.

The study’s at-risk criteria included symptoms, diastolic dysfunction, elevated calcium score, left ventricular ejection fraction below 60%, elevated NT-proBNP, atrial fibrillation and low stroke-volume index. Généreux said 96.4% of enrolled patients had symptoms, 72% had at least two at-risk features and 40% had at least three. The average patient age was 78 years.

According to Généreux, TAVR reduced the risk of death or heart-failure events, with or without hospitalization, by 33% at two years compared with clinical surveillance. The reported number needed to treat was 14. The result was primarily driven by a 52% reduction in heart-failure hospitalizations.

The TAVR group had no deaths or disabling strokes at 30 days, Généreux said. The study also showed an immediate improvement in KCCQ quality-of-life scores among TAVR-treated patients, while patients assigned to surveillance experienced declines before some later underwent valve replacement.

Among 371 surveillance patients, 204 underwent aortic valve replacement within two years, including 27% by one year and 57% by two years. Généreux said 81.4% of those who underwent valve replacement had progressed to severe aortic stenosis and had a Class I indication for intervention.

Moderate disease population and next steps

Généreux also discussed the ACTIVATE analysis, a real-world review involving data from 15 million patients across 50 U.S. centers. Among approximately 54,000 patients with moderate or severe aortic stenosis, 65% had moderate disease and 35% had severe disease, he said. Eighty percent of moderate aortic stenosis patients had at least one at-risk feature, falling to 70% when symptoms were excluded.

He said two-year mortality and heart-failure hospitalization rates among moderate aortic stenosis patients with at-risk features were close to those seen in severe aortic stenosis and roughly twice the rate observed in moderate patients without at-risk features.

Martin Leon, professor of medicine at Columbia and director of cardiology at NewYork-Presbyterian, said the findings could alter how clinicians classify and manage aortic stenosis. He argued that the disease exists on a continuum rather than in strictly defined mild, moderate and severe categories, and said patients with moderate disease should receive more comprehensive assessment at valve centers.

Dan Lippis, corporate vice president of TAVR at Edwards, said the PROGRESS trial was designed in collaboration with the FDA, though he did not provide a timetable for a potential indication expansion. He added that the recently updated Medicare national coverage determination includes language allowing reasonable and necessary applications of TAVR to be considered through work with Medicare Administrative Contractors, while noting that moderate aortic stenosis is not currently an approved indication.

About Edwards Lifesciences (NYSE:EW)

Edwards Lifesciences Corporation NYSE: EW is a medical technology company focused on therapies for structural heart disease and critical care. The company develops and manufactures products designed to treat conditions affecting the heart's valves, including aortic, mitral and tricuspid valve disorders.

Its portfolio includes transcatheter aortic valve replacement systems, transcatheter mitral and tricuspid therapies, surgical heart valves and valve-repair technologies. Edwards also provides related delivery systems and other medical devices used by physicians in minimally invasive and open-heart procedures.

Founded in 1958 by Miles Lowell Edwards, the company is headquartered in Irvine, California, and serves healthcare providers and patients internationally.

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