By AMANDA PEDERSEN
Medical Device Daily Senior Staff Writer
MIAMI BEACH There are a lot of appetizing data being served this week at the Transcatheter Cardiovascular Thereapeutics (TCT) meeting in Miami, but one of the main courses is clearly transcatheter aortic valve implant (TAVI), also known as transcatheter aortic valve replacement (TAVR). TCT, sponsored by the Cardiovascular Research Foundation (New York), dedicated a sizeable portion of the meeting to the current data on TAVI/TAVR featuring Edwards Lifesciences (Irvine, California) at the head of the table with its Sapien valve, with several other companies wrestling for a slice of the TAVI pie.
"We walked away impressed with the amount of time devoted to TAVR and believe physician interest remains high, especially expanding TAVR into a larger subset of patients (intermediate, low risk, valve-in-valve)," Glenn Novarro, a medical device analyst with RBC Capital Markets, noted in his TCT Day 1 takeaways report to clients.
Edwards was first to market in the U.S. with its Sapien transcatheter aortic heart valve initially approved for the transfemoral delivery approach (via the leg) in November (Medical Device Daily, Nov. 3 and Nov. 4, 2011). Late last week the company reported another big milestone for the Sapien valve, FDA approval to treat high-risk aortic stenosis patients with the device delivered transapically (through the ribs). The expanded indication opens up the procedure to a considerably broader group of patients (MDD, Oct. 22, 2012).
New data from the non-randomized PARTNER continued access registry for transfemoral and transapical approaches demonstrate that the favorable results achieved with TAVR in high-risk patients in the randomized, controlled trial are reproducible in a real-world setting, according to presentations at TCT 2012.
Murat Tuzcu, MD, professor of medicine, vice chairman of the department of cardiology in the Sydell and Arnold Heart & Vascular Institute, and an interventional cardiologist at Cleveland Clinic, presented three-year results from the PARTNER Cohort B trial, which found that TAVR yielded lower mortality rates after three years compared with medical therapy in patients deemed to be ineligible for conventional aortic valve surgery.
A total of 358 patients underwent randomization at 21 centers. At three years the estimated rates of death were 54.1% in the TAVR group and 80.9% in the standard therapy group. The rate of rehospitalization in the TAVR group was 42.3% compared to 75.7% in the standard therapy group.
"The three-year data continues to support the role of TAVR as the standard of care for symptomatic patients with aortic stenosis who are not surgical candidates," Tuzcu told Medical Device Daily on Wednesday. He added that the data underscores the importance of patient selection before TAVR and the need for aggressive management of illnesses after TAVR.
When asked by Bernard Gersh, MD, of the Mayo Clinic (Rochester, Minnesota) how the technology should be rolled out to the cardiology community in the U.S., Tuzcu emphasized the importance of the multi-disciplinary heart team program, not only for decision making but also for follow-up care. "We should not promote a procedure, we should promote a program of taking care of aortic stenosis patients."
TCT attendees were also reminded this week of the small, independent Danish trial presented last year that raised concerns about TAVI, particularly the transapical delivery approach. The researchers of that trial reported at last year's meeting that they had halted a study of the Sapien valve due to adverse events associated with the procedure. In the STACCATO trial, five of 34 patients who received the Sapien implant by the transapical approach experienced kidney failure, suffered a stroke, or died (MDD, Nov. 11, 2011).
This week at TCT, Leif Thuesen of the Aarhus University Hospital (Denmark) discussed the STACCATO trial and noted that the major issue was with paravalvular leakage. He said 43% of patients had minor leakage and 13% had moderate or severe leakage in the TAVR group compared to virtually no problems in the surgical group. He also said, however, that this may change with next-generation devices, such as the Sapien XT, and better pre-procedural assessment.
"There was a common theme for physicians to follow a 'transfemoral first' approach given lower mortality rates, as compared with alternative access," Novarro said. "However, the procedure has its limitations (most notably access size)."
While Edwards is still seen as the front runner in the TAVI market, several other companies are eyeing a piece of the TAVI pie.
St. Jude Medical (St. Paul, Minnesota) reported encouraging one-year results from its Portico TAVR first-in-man. The Portico valve is an 18 Fr nitinol self-expanding stent for transfemoral implantation that is designed to be repositionable, retrievable, and fully re-sheathable until fully deployed by the Ultimum introducer.
In the first-in-man experience at one-year, in the first 21 patients implanted with the device, there have been no deaths, no major strokes, no new pacemaker implantation, and very low levels of aortic regurgitation. There were, however, seven serious adverse events reported including GI distress, shortness of breath, hypothyroidism, fatigue, afib, and cerebrovascular ischemia.
What sets the Portico device apart from others in the space, according to St. Jude, is the fact that both bovine and porcine tissue are used with a stent design that features a skirt seating to conform around calcific nodules in the annulas to minimize paravalvular leakage (MDD, May 21, 2012). A transapical implant is also planned.
According to Larry Biegelsen, a medical device analyst for Wells Fargo, St. Jude continues to expect CE mark approval for the 23 millimeter version of the device later this year. "We would note that while the early data are promising, the 23 millimeter valve is a niche size that is appropriate for a small percentage of patients (about 20%), therefore, approval in Europe for the 23 millimeter valve is unlikely to generate significant revenue," he said in a report he released from TCT Tuesday.
Another company fighting for a seat at the TAVI table is Boston Scientific (Natick, Massachusetts) with its Lotus aortic valve system. According to Boston Scientific, the Lotus is a pre-loaded, stent-mounted tissue valve prosthesis and catheter delivery system for guidance and percutaneous placement of the valve.
Boston Scientific reported this week that its REPRISE I feasibility trial demonstrated successful deployment of the Lotus system in all patients, with "virtually no" paravalvular regurgitation through three months. The Lotus valve system is a second-generation TAVR technology designed to simplify and improve the TAVR procedure in patients with severe aortic valve disease, the company noted.
The trial results, presented by Ian Meredith, PhD, professor and director, Monash Heart, Monash Medical Centre and Southern Health Melbourne (Australia), highlighted the predictable and precise placement of the Lotus and a unique Adaptive seal feature designed to minimize the incidence of paravalvular leakage. These features will be further tested in the REPRISE II study (CE mark trial) which began enrollment this month, Boston Scientific said.
Also at TCT this week, Medtronic (Minneapolis) reported new findings from its CoreValve ADVANCE study for one-year survival and health-related quality of life (HRQoL).
Initial one-year results of the ADVANCE study revealed that patients experienced high survival rates, with one-year survival at 82.1% and one-year cardiovascular survival at 88.2%. HRQoL measures for patients in the ADVANCE study improved significantly at one and six months, compared with their status prior to receiving the CoreValve system. According to Medtronic, the ADVANCE study represents the largest, most rigorously collected evaluation of HRQoL findings published on TAVI. The study included 996 patients consecutively treated at 44 TAVI centers in 12 countries.
"Transcatheter aortic valve implantation already has been shown to improve survival compared with standard therapy, but quality of life can be at least as important as survival in elderly patients, especially since TAVI patients can be frail with multiple comorbidities," said Johan Bosmans, MD, professor at the University Hospital of Antwerp (Belgium). "We are extremely proud of this data which confirms that the benefits of transcatheter aortic therapy extend beyond survival even in this challenging patient population."
Biegelsen noted that Medtronic's filing strategy suggests a late 2014 U.S. approval. The company completed enrollment in the inoperable arm of its pivotal U.S. trial for CoreValve in January and completed enrollment in the high-risk arm in August. "It is our understanding that FDA will review these two arms as one package," Biegelsen said.
Another noteworthy company at the TAVI table is Direct Flow Medical (Santa Rosa, California) which reported that its DISCOVER CE mark trial met its primary mortality endpoint (freedom from all-cause mortality from procedure to 30 days) and demonstrated that greater than 95% of patients had mild or less aortic regurgitation, and no patients experienced vascular complications.
Amanda Pedersen, 912-660-2282;
Published October 25, 2012