SAN FRANSISCO—An estimated 10,000 transcatheter heart valves have been implanted in patients with critical valvular aortic stenosis, and the researchers, who have their eyes on U.S. approval, are now seeking to standardize the techniques and trial expectations, according to a presentation by Martin B. Leon, MD, at the 21 st annual Transcatheter Cardiovascular Therapeutics (TCT) symposium.
Leon, who is associate director of the Center for Interventional Vascular Therapy at New York-Presbyterian Hospital/Columbia University Medical Center in New York City and chairman of the Cardiovascular Research Foundation that runs TCT, explained that this “exploding” technology has garnered “enormous” attention, and this is an era of evolution in medical therapy for the common disease. “However, it remains critically important for the researchers to evaluate the data, and put into perspective how these new technologies are going to be and should be used,” he noted.
The current clinical data for the two devices approved in Europe—Edwards Lifescience’s Sapien and the ReValving system from CoreValve, acquired by Medtronic in February— first underwent small-sized first-in man trials. “These feasibility studies helped us refine the technology, as well as the techniques, and led to the European approval studies,” Leon said. “Now, pivotal, randomized controlled trials have begun for approvals.”
Edwards is currently enrolling patients in the PARTNER trial (Placement of AoRtic TraNscathetER valve trial Edwards’ Sapien transcatheter heart valve), of which Leon is the principal investigator, in the U.S. Also, Medtronic has completed enrollment in a non-U.S. clinical evaluation, which is also currently underway.
Leon explained the field is in a “rapid period of data accumulation,” adding that the Edwards’ device will be featured in approximately 80 peer-reviewed journals in 2009.
“The problem is that interpretation of these data has been something of a conundrum,” according to Leon. “These early trials were understandably, a little chaotic, reflecting very frequent changes in technology, procedural methods and data collection processes (small sample sizes and difficult to pool or compare data sets).”
He added that the study endpoints were never clarified or standardized. “We took an interventional approach, which was casual, and did not assess the surgical guidelines,” Leon said. “We even created terms that we could not accurately define, such as ‘vascular complications.’ As a result, it was difficult to properly determine the results."
It was also an inconsistent use of coordinating centers and core labs, accompanied by poor follow up in many of these studies, he explained. “If a surgeon implants a new surgical valve, they are mandated to perform annual echo follow up on these patients to assess subtle features of durability. We need to be doing the same thing for the transcatheter valve.”
Of note, these patients also are incredibly sick—elderly, infirmed and co-morbid patients with critical aortic stenosis.
Endpoints have been incredibly controversial in this growing field. Leon explained that even the simplest endpoint of death is complicated by the cause of death, and because death is defined differently by various “definitive sources, such as the Academic Research Consortium (ARC) definitions and the 2008 guidelines from the Society of Thoracic Surgeons (STS). “These typify the problems we have in trying to compare these new technologies against the current standards of medical therapy or surgical therapy,” he said.
In fact, a 2009 EuroInterventions editorial expressed a ‘call to arms,’ inviting industry and physicians to set a standard of clinical evaluations, both immediate and over time. It read that “we cannot get woefully enthusiastic about this new technology, until we properly collect data to accurately evaluate its safety and effectiveness.”
The development of ARC was to develop a collaboration between academic researcher organizations in the U.S. and Europe, with representatives from the FDA and various medical device manufacturers, in order to produce and publish a standardization of clinical endpoints.
Based on this model, the same group of representatives have come together to form the Valve Academic Research Consortium (VARC), in an attempt to harness the positive methodologies of the ARC process and to customize it for this specific field. In addition to the previous collaborators, multiple societies have also