Hi, I'm Jeffrey Popma. I'm an interventional cardiologist at the Beth
Israel Deaconess Medical Center in Boston and a professor of medicine at
Harvard Medical School. What I'd like to discuss today is the
results of what I think is one of the most transformative trials that we've
seen here at the American College of Cardiology meeting and that is the
Evolut Low Risk randomized clinical trial, a trial that compared
transcatheter aortic valve replacement to surgical aortic valve replacement. As a
bit of background, this has been an investigator group that has been forming
for the last ten years. When we first met in 2010, we didn't know how transcatheter
aortic valve replacement was going to compare to surgery.
We started our initial study with the patients who are at extreme risk for surgery,
and quickly moved on to patients who are deemed to be high-risk for surgical
aortic valve replacement. In that randomized trial, led by Dave Adams and Mike Reardon,
we found that, in fact, for the first two years there was a lower mortality rate
with transcatheter valve replacement than with surgery. At five years later,
presented by Tom Gleason, there wasn't a significant difference between the two,
but nevertheless during that early period of time, there was a mortality
benefit associated with transcatheter valve replacement compared
to surgery. We then moved on to the SURTAVI trial, a trial in intermediate
risk patients, and in those intermediate risk patients we found at two years the
rate of disabling stroke or all cause mortality was was not inferior
with TAVR surgery, a very important finding, again published by Dr. Reardon
in the New England Journal of Medicine. And that brings us to today. Over the past
two years, we've been recruiting patients who are deemed by a heart team to be low
risk of surgical aortic valve replacement to either transcatheter
aortic valve replacement or to surgery. And what do we mean by that? Our heart teams
met at all of our institutions, we deemed that the patient was going to have a
less than 3% 30-day operative mortality, and if the patients met that criteria,
they were enrolled in the clinical trial. We then enrolled over 1,400 patients
into this randomized trial, equally divided between transcatheter valve
replacement and surgery. We performed this study at the most phenomenal clinical
sites across the world, 80 of them, who then used their best surgical approach
and those patients randomized to surgery, and their best practice
technique for those patients who are randomized to transcatheter aortic valve
replacement. We did something, I think, very important, we picked as a primary
endpoint all cause mortality or disabling stroke at two years, and that
endpoint was an important endpoint for us because we felt that we needed
to prove that there was unequivocal non-inferiority of our transcatheter
valve versus surgery valve, because we felt that it was going to change the
field, that that that we had to have an absolutely durable outcome, a hard
clinical outcome, something that no one would really dispute. The patients
who enrolled in the study were 74 years old, they had an average STS score of 1.9,
which really meant that they were, in fact, a low risk surgical group. Here's
what we found. We found that at using a Bayesian analysis, when 850
patients had actually achieved a one-year outcome, we found that
extrapolating those results to the entire cohort of patients, for all 1,403 patients,
that at 2 years the predicted probability of death or all-cause
stroke, or a disabling stroke, was 6.7% in the surgery group and 5.3% in the
TAVR group, not strongly non-inferior and meeting are our primary endpoint.
But then we looked at a variety of secondary endpoints, and I'll just
summarize them. We asked the question how safe is TAVR? We
understand now that the mortality rate was extremely low at 30 days, in one
year, in both the surgical groups and the TAVR group, but our pre-specified, 30-day
safety endpoint was better with TAVR. And what was included in that? Mortality,
disabling stroke, atrial fibrillation, acute kidney injury — all those endpoints
that we look at from a secondary standpoint were actually better for
patients who were treated with TAVR than surgery. What was different? There
were more pacemakers in those patients are treated with TAVR, we've known that,
but that was about the only deleterious or downside effect of treatment with
that device and we've got ways, as I'll discuss, to approach that.
Otherwise, out to two years, there was a significantly lower reduction in
disabling stroke, similar mortalities, and any way we looked at the data, we found
that TAVR was a preferred option. Now, we did one more thing. We said, let's look at
now how often the patient needs to come back to the hospital in the first year,
and what we found was that that within the first year there was significantly
lower rates of rehospitalization — heart failure rehospitalization — in patients
who were treated with TAVR than surgery, so the composite of death,
disabling stroke, all hospitalization, in the first year significantly lower with
TAVR. So, what are the caveats? Well, we didn't put patients in the study who
were candidates for a mechanical aortic valve. We didn't put patients in the
study who had bicuspid aortic valve disease, and in general, as the
operations went through, 99% of TAVRs were performed from the
transfemoral approach, which means we didn't put many patients in who had
really prohibitive iliofemoral access. So, what does this mean for our patients?
Well, in this large-scale randomized trial with an endpoint of all-cause
mortality of disabling stroke at two years, we showed that TAVR
was not inferior to surgery, a very, very important endpoint for our
patients. Secondly, at 30 days, we found that TAVR was a safer procedure, with
lower rates of disabling stroke, lower rates of acute kidney injury, lower rates
of life-threatening or disabling bleeding, albeit at higher rates of the
need for permanent pacemakers and for residual aortic regurgitation. In aggregate,
patients now can choose between these two different therapies — a lesser
invasive approach or a more invasive approach, but probably the evidence falls,
in fact, in favor of TAVR. One final point: with this self-expanding Evolut
technology that was used for the trial, we found that the gradients were
significantly lower at all time points out to two years with TAVR than surgery,
and that the aortic valve areas were higher with TAVR than with surgery all
the way out to two years. This resulted in a fourfold reduction of the degree of
severe prosthesis–patient mismatch at one year in patients who are treated with
TAVR and these better valve hemodynamics, we think, may have a very
beneficial effect on a younger population treated with this device. We
hope that these results, now published today in the New England Journal of
Medicine, available both in the primary manuscript and in an extensive
supplement, will support the fact that in patients who are deemed to be low risk
for surgical valve replacement, TAVR is, in fact, the
preferred therapy for the appropriate patients.