Hi everyone. My name is John Jarcho. I'm a deputy editor at the New England Journal
of Medicine and a cardiologist. I'm delighted to be here today on the floor
of the ACC to tell you a little bit about some of
the things that are going on at the meeting, and also to tell you about the
MOMENTUM 3 trial that we just published online on our website this
morning. Yesterday in the opening showcase session of the meeting, there
were a couple of very interesting randomized trials that were presented.
The first was the ODYSSEY Outcomes trial, which is a randomized trial of the PCSK9
inhibitor alirocumab compared to placebo in patients with a recent acute
coronary syndrome. The trial enrolled almost 19,000 patients and nearly all of
the patients were receiving high doses of statin therapy, despite which they
continued to have an elevated level of LDL cholesterol. At a median follow-up of
2.8 years the LDL cholesterol level had dropped to 53 mg/dL
on average in the alirocumab group and 101 mg/dL on
average in the control group. There was also a significant reduction in the
primary outcome measure of coronary heart disease, death, myocardial
infarction, stroke, or unstable angina requiring revascularization. Last year
the New England Journal published the FOURIER trial, which is another
randomized trial of a different PCSK9 inhibitor evolocumab in patients with
stable coronary disease. That trial also showed a benefit of PCSK9 inhibition on
top of statin therapy. Therefore the ODYSSEY Outcomes trial
suggests that the benefit previously shown of the
PCSK9 inhibitor class on patients with stable coronary disease can also be
extended to patients who've had a recent acute coronary syndrome. The second trial
that was presented in the opening showcase was called the VEST trial. The
V trial was a trial of a wearable defibrillator vest versus standard care
in patients with an acute myocardial infarction and an ejection fraction of
35% or less. People who have followed this field for a while will
know that back in 2002 the MADIT-II trial demonstrated that, in patients with
a previous myocardial infarction and a reduced ejection fraction, an implantable
cardioverter defibrillator, or ICD, actually reduces mortality over the long
term. This observation was the basis for the current practice of implanting
defibrillators in most patients who have had a myocardial infarction and have a
reduced ejection fraction. However, a few years after the MADE IT 2 trial, a
couple of subsequent trials produced surprising results — those being the
DINAMIT and IRIS trials — those trials showed, surprisingly, that for patients
within the first month after an acute myocardial infarction, an implantable
cardioverter-defibrillator did not produce a benefit on all cause mortality.
This result has been a subject of debate ever since the observation was made, and
it has led to guidelines recommendations that defibrillators should not be
implanted in patients until after the first month following an acute
myocardial infarction. This has then posed the problem for clinicians: how do
we manage these patients in their first month after an MI, since they are
presumably at high risk of ventricular arrhythmic death, but apparently do not
benefit from an ICD. For some clinicians, the solution to this problem has been to
recommend the wearable defibrillator vest as a means of protecting the
patient against arrhythmic death during that first month. The VEST trial examined
this hypothesis by randomizing the group of patients with acute myocardial
infarction and an ejection fraction of 35% or less to either the
wearable defibrillator vest or to standard care. Disappointingly, the
finding that was made for the primary endpoint in this trial was that the
defibrillator vest did not reduce the risk of sudden cardiac death or
ventricular arrhythmic death in this population of patients. There was what
appeared to be a nominal benefit of the wearable defibrillator vest on a
secondary outcome, that being all cause mortality.
However, the p value for benefit on this secondary outcome was 0.04, not corrected
for multiple testing, which means that there is uncertainty about whether the
wearable defibrillator vest actually does benefit patients with respect to
all cause mortality in this setting. There's also the question, which remains
unanswered, of how a device that should only have an impact on
arrhythmic death could reduce all cause mortality but not sudden cardiac death. I'd also
like to talk a little bit about the MOMENTUM 3 trial which was presented
in a late-breaking clinical trial session this morning. MOMENTUM 3 was
a randomized comparison of two left ventricular assist devices — the HeartMate
2 device, which is an axial flow pump, and the HeartMate 3 device, which is a
centrifugal flow pump. The HeartMate 3 is the newer of the two devices and it was
developed specifically to try to overcome a particular problem with the
HeartMate 2 device which is a propensity for that device to develop ventricular
assist device thrombosis; that is, thrombosis within the pump leading to
pump malfunction and the need to remove it surgically and replace it. In the
MOMENTUM 3 trial there was a significant benefit of the HeartMate 3 when compared
to the HeartMate 2 on the primary outcome which was survival free from
either disabling stroke, or the need for a second operation to replace or remove
the pump. The benefit was entirely due to a reduction in reoperations and
because those reoperations are typically due to pump thrombosis the
trial did in fact demonstrate the hoped-for benefit of the HeartMate 3,
which is a reduction in LVAD thrombosis. This device represents a new paradigm in
the field of mechanical cardiac support. For people who are interested in reading
the full results of HeartMate 3 trial, the article is now available online at
the New England Journal of Medicine website or if you're here at the meeting
you can come by the NEJM booth and pick up a print copy of the MOMENTUM 3 trial
at booth number 1344. I'd like to thank you for the
opportunity to tell you a little bit about what's been going on at the ACC,
and I'd like to remind you to stay tuned because there will be some additional
simultaneous publication of late-breaking clinical trials coming
during the rest of the meeting. Thank you very much.