First TAVR for Aortic Regurgitation Moves to Phase 3 Trial

WASHINGTON — A phase 3 randomized trial will soon begin for the first transcatheter aortic valve replacement (TAVR) device for the treatment of aortic valve regurgitation after promising results in a 2-year initial study.
If this novel option performs as well as surgical aortic valve replacement (SAVR) in the coming trial, the regurgitation-specific valve “will be well positioned to become the preferred therapy for this indication,” said Torsten P. Vahl, MD, director of Translational Research at the Structural Heart and Valve Center at Columbia University Irving Medical Center in New York City, who presented the 2-year data at Transcatheter Cardiovascular Therapeutics (TCT) 2024.
The experimental device is the JenaValve Trilogy Heart Valve System (JenaValve Technology, Munich, Germany). Rather than the new valve expanding in the aortic annulus, this porcine pericardial valve clips to aortic leaflets, which minimizes stress on cardiac and aortic structures and preserves the potential for future coronary interventions.
Novel Valve Clip
The uncontrolled, single-arm study, called ALIGN AR, enrolled 180 patients with grade 3 or 4 aortic valve regurgitation, which means moderate to severe aortic insufficiency with at least a 40% regurgitant fraction, and who were considered high risk for surgery.
Outcomes were compared to baseline at 30 days and 1 year for prespecified performance goals based on historical regurgitation outcomes. The most important of these was mortality, for which the goal at 1 year was < 25%. The data at 2 years provide more information on longer-term safety and efficacy.
When the 1-year data were first presented last year and subsequently published in The Lancet, the mortality rate was 7.8%. Now at 2 years, the mortality rate has climbed to 15.4%, but this was driven by non-cardiovascular events, and it still remains well below the prespecified goal, Vahl reported.
The rate of cardiovascular mortality, which was 6.2% at 1 year, remained relatively stable climbing to just 7.4% after 2 years. The rate of nondisabling stroke remained unchanged at 4.1% from year 1 to 2 and that of disabling stroke climbed from 1.7% at 1 year to 2.3%.
The rate of new pacemakers, surgery, or other major interventions related to the device remained unchanged from year 1 to 2. The rate of myocardial infarction climbed from 1.2% to 1.9%, and the rate of major bleeding climbed from 5.6% to 7.0%.
Valve performance also improved over time. By day 30, 83.3% of patients had achieved no or trace regurgitation. This climbed to 91.8% at 1 year and 95.6% at 2 years, Vahl reported.
Improvement Persists at 2 Years
At enrollment, 32% of patients were in New York Heart Association (NYHA) class II heart failure, while 63% were in class III and 5% were in class IV. By 30 days, 54% were in NYHA class I heart failure, 37% were in class II, and only 10% were in class III. No patient remained in NYHA class IV heart failure. By 1 year, 60% were in NYHA class I heart failure. There was no substantial change at 2 years.
This is consistent with highly favorable and progressive improvements in left ventricular remodeling. For left ventricular end-systolic diameter and volume, a large improvement relative to baseline at 30 days was followed by further improvements at 6 months and 1 year. Although no further improvement was seen after 2 years, there was also no decline.
The large improvement in left ventricular mass index at 30 days was also followed by further improvements at 6 months and 1 year, but in this case, another substantial improvement was observed at year 2.
The median improvement in the Kansas City Cardiomyopathy Questionnaire quality-of-life index improved from 55.3 at baseline to 77.7 at year 1 and 78.7 after 2 years.
A randomized noninferiority trial called ARTIST trial is scheduled to begin enrolling around 1000 patients in 2025. This trial will compare the novel valve with SAVR. The composite primary endpoint includes death, stroke, and urgent cardiac revascularization.
Facing SAVR Next
Katherine Harrington, MD, a cardiothoracic surgeon with Baylor Scott & White Cardiac Surgery Specialists in Plano, Texas, called ALIGN AR a “landmark study” because a TAVR specific to aortic regurgitation is “an important unmet need.”
Harrington said she was already impressed with the previously reported 1-year results, but the 2-year data provide reassurance that the benefits persist and indicate the device has the potential to pass regulatory approval.
Harrington said a positive result in the ARTIST trial would be an important step forward for the treatment of aortic regurgitation. “We are all excited about the possibility of an on-label valve,” she said. Although the number of patients who need valve repair for aortic regurgitation is smaller than the number of patients who need new valves for aortic stenosis, the current options are limited, according to Harrington. She said this novel design might address some of the limitations associated with existing TAVR devices when they are used off-label for regurgitation.
 
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