The nature of U.S. transcatheter aortic valve replacement (TAVR) shifted dramatically in mid-June when the Food and Drug Administration, in two separate actions timed just days apart, approved marketing of next-generation models for the only two transcatheter aortic valve replacement systems on the U.S. market.
For inoperable or high-risk patients in came the Edwards Sapien 3 and the CoreValve Evolut R systems, and out went the Sapien XT and the original CoreValve. In the process the transcatheter aortic valve replacement (TAVR) procedures available to American patients on a routine basis became smaller – meaning more likely to use transfemoral approaches, less likely to cause substantial paravalvular leak, less likely to cause stroke, and in the case of the Evolut system also became repositionable and less likely to result in the need for a pacemaker.
With approvals of these two latest-generation devices, in both cases based on follow-up data of only 30 days, “we have really expanded the types of patients who can be treated with TAVR in the U.S., and we can do it with better products and get better outcomes. I am thrilled this technology will be available to patients,” said Dr. Jeffrey J. Popma, a lead investigator for the Evolut U.S. pivotal trial and professor of medicine at Harvard University in Boston.
Mitchel L. Zoler/Frontline Medical News
Dr. Jeffrey J. Popma
The pair of approvals were also notable as clear demonstration that the FDA was willing to base its decisions on 30-day follow-up data, a step closer to the approval model it applies to heart valves placed using open surgery. Perhaps most attention-grabbing of all, the FDA based its approval of the Evolut system on data from a total of 151 patients, with 60 coming from the ex-U.S. trial designed to secure a CE mark in Europe, and the other 91 patients the first ones enrolled in what was designed to be the U.S. pivotal trial for Evolut, with a planned enrollment of 250 patients that had almost fully filled by mid-June.
“This was a really good week for the FDA,” said Dr. Popma. “The FDA approved devices with reasonable assurance of safety and efficacy but without the burden of requiring 1 or more years follow-up. We are seeing a changed FDA,” he declared in an interview.
Although the full dataset for all 151 patients that the FDA used to approve the self-expanding Evolut system has not yet been released, investigators from the U.S. trial say data from their first 91 patients looked similar to the 60 patients in the CE trial, the results of which appeared in a poster in March at the annual scientific sessions of the American College of Cardiology.
The CE trial enrolled 60 symptomatic extreme- or high-risk patients at six centers in Australia, New Zealand, and the United Kingdom, who averaged 83 years old and had an average Society of Thoracic Surgeons predicted mortality estimate of 7%. Fifty-nine of the 60 patients (98%) had their TAVR done via the transfemoral route, and during 30-day follow-up no patients died and none had a stroke. The researchers identified a moderate or severe paravalvular leak in 3% of patients after 30 days, and 12% of patients had a new need for a pacemaker. By comparison, in the CoreValve pivotal trial for the first-generation version of this self-expanding valve, death occurred in 3% of patients after 30 days, major strokes in 4%, moderate or severe paravalvular leaks occurred in 9%, and 20% of patients by that point had required placement of a new pacemaker (N. Engl. J. Med. 2014;370:1790-8).
Dr. Mathew R. Williams
The striking reductions in more severe paravalvular leaks and in the need for a pacemaker likely related at least in part to the ability to reposition the Evolut valve during placement as long as the valve was not more than 80% deployed and as long as retrieval was not attempted more than three times.
Repositioning is “huge” said Dr. Mathew R. Williams, chief of adult cardiac surgery and director of interventional cardiology at New York University, and one of two lead investigators on the U.S. CoreValve Evolut R pivotal trial. “We don’t need to use it most of the time, but having that ability reduces stress and helps make the operator more comfortable,” he said in an interview. The more optimized positioning allowed by the recapture feature likely helped minimize both paravalvular leaks and the valve’s ability to trigger an arrhythmia and need for pacing. In the CE trial the operator used the repositioning function in 15 patients (25%) for a total of 22 repositioning events.