Arguably the hottest trial at last week’s Transcatheter Cardiovascular Therapeutics (TCT) conference was PARTNER. The PARTNER trial compared outcomes between standard therapy for patients with inoperable severe aortic stenosis and transcatheter aortic valve implantation (TAVI). TAVI is a new procedure where a bioprosthetic aortic valve is inserted either femorally or transapically by catheter and then implanted within the native aortic value. Previous to the release of PARTNER, the assessment of efficacy and safety of TAVI was confined to registries and various modest-sized Phase I trials.

PARTNER is a landmark trial in the management of patients with severe AS. Median survival time for patients receiving standard treatment is two years. TAVI resulted in 45% reduction in all-cause mortality and 61% reduction in cardiovascular mortality at 1 year in high-risk AS patients compared with standard therapy.  Further support of TAVI was that echocardiographic criteria such as aortic valve area and mean aortic valve gradients all improved as did symptom criteria such as the patients’ NYHA class.

Important cautions were noted in PARTNER: although the procedure can reduce mortality, there was a significantly higher risk of major vascular complications and major bleeding, and a trend towards a higher risk of major stroke in the TAVI arm.

Thus, while the overall results are very exciting, the high complication rate should temper overenthusiastic tendencies toward the aggressive use of TAVI. The results also should encourage the development and application of adjunctive intravascular techniques to diminish the stroke risk and, clinically, employ better case selection for either the femoral or transapical approach to minimize the vascular complications.

Thoughts
Although the findings of the study itself are clinically important, the regulatory background in which TAVI finds itself deserves special comment. TAVI is not yet approved as a treatment option in the U.S., although it is extensively used in Europe and other areas of the world.

This approval conundrum brings up two thoughts to mind:

1. TAVI already is highly in use in Europe. A TAVI registry in Great Britain for example already has over 1,200 patients enrolled. Is this an indication that the U.S. has lost its once-felt leadership in innovation and technology? The U.S. health care system, for all its flaws, has been considered the leading innovator in cardiovascular disease due to our highly skilled and visionary cardiovascular specialists working collaboratively with our industry partners.  Does this imply that our colleagues at the FDA should pursue additional avenues to foster innovation and assess safety and efficacy of new technology?  Are there ways the FDA could decrease the evaluation time necessary prior to the release of new technology into the marketplace if we had better post-market device surveillance routinely put into place?
   
   
2. Will the PARTNER trial alone be enough to earn FDA approval? And if (or as most of us feel when) approved, what can the FDA and  professional societies such as the ACC and SCAI do to help ensure patient safety with the diffusion of this new technology into the community? Clearly, interventionalists who perform TAVI will need special training, and the FDA likely will need to set out criteria for who can perform TAVI to ensure competence in this area. The ACC through its Interventional Council and competency and training documents -- along with our partners at SCAI and industry itself -- will all play an important role in ensuring patient safety as TAVI use is approved.
   
   FDA also will clearly need to monitor adverse outcomes and communicate how these adverse outcomes can be minimized.  Creating a TAVI registry within our NCDR suite could help implement the rigorous post-market surveillance desired as well as provide rich clinical information that could advise clinicians, the FDA, and payers for better patient selection for TAVI use. Participation in this registry might have additional appeal to interventionalists if it means they can have earlier access to TAVI’s innovative technology. The PARTNER trial well demonstrates the partnerships needed between industry, the FDA, professional societies and payers to be able to provide our patients with practice innovations in a safe and effective manner and in a timely fashion.

What are your thoughts on the trial and its implications? You can also comment on the CardioSource Trial Summary.

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