My name is Mike Mack, and I'm a cardiac surgeon at Baylor Scott & White in
Dallas. I am the co-principal investigator of
the PARTNER 3 trial, along with Marty Leon of Columbia University. We're here
at the New England Journal booth at the American College of Cardiology 2019 in
New Orleans. We have just presented the results of the PARTNER 3 trial, which is
TAVR, or transcatheter aortic valve replacement,
compared with surgery in low surgical risk patients. This is available
online now at the New England Journal of Medicine. There have been a series of
PARTNER trials — 5 trials over the last 12 years. They have enrolled a total of
9,000 patients comparing TAVR with either medical therapy in
inoperable patients, or compared with surgery in high surgical risk and
intermediate surgical risk patients. This trial, the PARTNER 3 trial that was
presented today, compares surgery with TAVR in low surgical risk patients
meaning an STS predicted risk of mortality of under 4%. This represents
the largest group of patients currently undergoing surgery. There were a thousand
patients randomized at 68 sites in the United States, and Japan, Australia, and
New Zealand. About 98% of the patients were enrolled in the United States. The
primary endpoint of the trial was a one-year composite of death, stroke, and
need for repeat hospitalization. The follow-up was 98.5%
complete, and the findings of the trial was that TAVR met the first
trial criteria of being non-inferior to surgery, and in the second analysis,
it actually turned out that TAVR was superior to surgery for that primary
endpoint at one year. There was a 46% reduction of the primary endpoint at one
year with TAVR compared with surgery. Now,
this wasn't just driven by repeat hospitalization. Death at one year
favored surgery, but didn't quite reach statistical significance.
There were two in-hospital deaths with TAVR,
there were four in-hospital deaths with surgery, there were five
deaths at one year in the TAVR arm, and eleven deaths at one year
in the surgical arm, so the p-value in that was 0.09, but numerically it favored
TAVR. Stroke was significantly lower with TAVR than with surgery, both at 30
days and at one year. The composite of death and disabling stroke was 1% at 1
year with TAVR, which was less than the 2.6 percent with surgery, and then repeat
hospitalization was lower again in favor of TAVR. There were six pre-
specified hierarchical secondary endpoints and all of those favored
TAVR and included such things as post-operative atrial fibrillation,
hospital stay. One of the big concerns has been need for new pacemaker
with TAVR, and it turns out that there is no
significant difference at one year between the need for permanent pacemaker
with TAVR compared with surgery. Now, there were a couple of areas in
which surgery actually looked better, and that is that the gradients were lower
and the aortic valve area was greater with surgery than with TAVR, which is
the first time this has been seen in any of these randomized trials.
The likely explanation for that is that we emphasized at the outset of this
trial that our surgeon investigators should put in as large a valve as
possible and about 80% of the surgical valves were size 23 or greater, so we
think this is at least a partial explanation as to why the results of
surgery looks so good. The other instance in which surgery
looked better was new left bundle branch block occurring afterwards. It occurred
in about 25% of of TAVR patients, and less than 3% of surgical patients. The
significance this is unknown but there is a little bit of concern that a higher
instance of left bundle branch block with TAVR. So the conclusions of the
trial is that the surgery, the TAVR, was significantly better in surgery in the
1-year primary outcome. Now, of course, there's important limitations to any
trial, to any randomized trial, including this one, and the first is that follow-up
is only one year, and and the concern that's going to be raised is, well, what
do we know about durability of the TAVR valve? Well, it is an
appropriate concern and because of that, all patients are going to be followed
annually for 10 years, so we will then know the results of durability, of both
TAVR valves and surgical valves, which, by the way, we really don't know what the
long-term durability is of surgical valves, so we'll know the results both
absolutely and relative to one another by 10-year follow-up with this. The
second is that this was a single device performed by expert operators in
experienced centers. Now, there was a presentation that
immediately followed this looking at the self-expanding valve, which showed it was
inferior to surgery, so it made be a class effect and not just a device
effect, but whether this expands to all centers, or just more experienced centers,
remains to be seen. The third is that you had to be able to have this performed by
a transfemoral access, and if you needed an alternative access this was not
included in the trial. Fourth, bicuspid aortic valves were excluded from the
trial and so we have to be careful in terms of being able to extrapolate,
or generalize, these results to patients with bicuspid disease, and indeed,
probably a randomized trial would be appropriate in this patient population.
So I think there's significant clinical implications to the studies presented
today, and that is that TAVR may well become the preferred therapy in low-risk
patients due to an extremely low death rate, extremely low stroke rate, and low
rate for need for repeat hospitalization. Now, the surgical results were excellent.
They were better than what was predicted, so it's not like the surgical control
arm wasn't great — it was great, and even with how well the control arm
performed, TAVR actually performed even better, and I think the questions will
now be raised is rather than who's a candidate for TAVR, it's going to be
who are the patients that SAVR is still going to be the
most necessary treatment, and I think from the inclusion/exclusion criteria
the trial we can begin to answer that question. Right now, bicuspid valves,
patients with significant severe left-ventricular outflow tract calcium, low
lying coronary arteries, aortopathy. So I think
the results presented today will cause a sea change. It is the fifth in a series
of trials in the PARTNER series and represents the largest group of patients,
and the fact that after both presentations this morning the audience
gave a standing ovation, I think speaks to the impact, or potential impact,
of these trials. So again, these results are available on the New England Journal
website at NEJM.org.