ESC 2019 – THEMIS, THEMIS-PCI, DAPA HF

ESC 2019 – THEMIS, THEMIS-PCI, DAPA HF


(gentle piano music) – We are here at the European
Society of Cardiology meeting in Paris, France. And I’m incredibly delighted to be able to introduce
myself, Ivor Benjamin, immediate past president of the American Heart Association, and my colleague and
friend, Dr. Bob Harrington, president of the American
Heart Association. Bob, we’re going to review
some amazing science. – Yeah, we sure are.
– That actually, came out today. And I think that, you know, we have obviously picked a few. But why not tell us a little
bit more about THEMIS. – Well, it’s been a great day. And this is truly hot off the press, these trials were literally just presented in the last hour. And the three we’re going
to talk about are THEMIS, THEMIS-PCI, and DAPA HF. – You got it. – And these are really important and interesting, Ivor, I think, because all of the trials involve drugs which are commonly used. And so, these are
potentially practice changing or at least practice influencing. And we should be able to
think about them immediately. So let’s talk about THEMIS first. – You do that. – In full disclosure,
I was an investigator in THEMIS, was a member of
the executive committee. And, it involved an anti-platelet
drug called ticagrelor. I was also the co-investigator
of the big PLATO study with ticagrelor, which
actually we presented at these meetings 10 years ago. At this meeting. – And there’s still more work to be done? – And there’s still more work to be done, that was part of the point, was, there has been a tremendous
amount we’ve learned about using ticagrelor, it’s a
P2Y12 inhibitor, as you know. Used in people with coronary
disease, undergoing stenting, people with acute coronary syndromes. And THEMIS, what we were interested in, is, in the group of
patients with diabetes, so a high risk group
of patients clinically, who have had coronary disease but are at the point of stability, so stable coronary disease. Many, if not most of those people are just on asprin. Does the addition of ticagrelor
to their medical regimen improve outcome relative to placebo? Big trial. – Important question. – Important question because
it’s a big group of patients. Over 19,000 patients randomized, followed for over three and a half years. So, big population, studied
for a long period of time, good adherence to the studied medication and what was observed? A modest benefit of ticagrelor. By modest we mean, you
know, 13, 15% range. Relative. And statistically significant, are reducing the compositing point of cardiovascular death and mild stroke. But, that came, also, with an increased risk of bleeding. And so you have a modest benefit, an increased risk of bleeding, if you think about it from a net clinical benefit perspective, there’s really no difference. You’re trading off limited bleeding for that little bit of ischemic benefit. But, as part of the THEMIS study,
we’re particularly interested in asking the question, what about the group of patients who underwent PCI in the past who we know took dual antiplatelet therapy for some period of time? – So just set it up, we’re
talking about risk benefit. – Yes. Exactly.
– Okay. (he laughs) – And in acute coronary
disease, as you know, it’s very definable. – You got it. – The benefit is
preventing ischemic events. The risk is causing bleeding. And how do you weigh those two? – You got it. – So, in THEMIS PCI, this
was a pre-stated hypothesis of the larger study,
what about those patients that got into THEMIS as evidence that they’d had coronary disease because they’d had a private PCI? And we know that those
patients might be different than patients who didn’t get a PCI. We also know that they probably tolerated DAPT at some point.
– At some point, absolutely. – So, of that 19,000, over
11,000 of those patients had had a prior PCI. So, big sample. – Big samples.
– Big trial even by itself. – So we have to really be able to have some level of confidence. – Exactly. And particularly when you
look at the two together. And here we see something different than we see in the overall trial. In the overall trial
there’s a modest effect, when you look at the
patients with prior PCI, bigger effect, still a modest
increased risk of bleeding, but now you see net clinical benefit. More benefit than risk.
– There you go. – And so I think for me,
wrapping that all together it says that in the group patients who have stable coronary disease and who have had a prior PCI, that population has, and has diabetes, that population has a risk attached to it that the longer term administration of dual antiplatelet therapy
ought to be considered. And Ivor, I think we can
put this in the context of things like the PEGASUS trial, the DAPT trial, which looked at long term dual antiplatelet therapy. That there is a high
risk group of patients. And utilizing risk scores can be helpful, utilizing prior PCI or not, in the face of diabetes can be helpful, but certain patients
should get consideration for prolonged dual antiplatelet therapy. – And I think that’s the main point that you’re really getting at. It’s that subset of patients and we’ve got to really be
able to do randomized trials. With sufficient confidence
that you’ve got the numbers to be able to, with some degree, and I would suspect that this
will even get into guidelines at some future point. – Well, I think this is the kind of trial that guidelines will certainly consider. As one of the investigators
as I said at the outside, I would hope that these
are the kind of data that the guideline writers will evaluate and take into consideration
when they’re thinking about who do we treat with long term
dual antiplatelet therapy? – So, the management of patients with ischemic heart disease
continues to evolve. And it’s that complementary
avascularization plus antiplatelet therapy. – And always assessing risk for both ischemic events and bleeding. So if you have somebody
who’s at high ischemic risk, and low bleeding, then you might have a little more confidence
to use aggressive therapy. You have somebody very high bleeding risk, not so high ischemic risk, avoid them. – Makes good sense to me and I think that this is going to be impactful for many of our patients
and like you said, something for future guidelines
committees to consider. Let’s talk a little bit about DAPA HF. – Yeah, DAPA HF, I think may have been the highlight of the day. – Okay. – Because, a couple of things.
– Just remind our viewers about DAPA HF. – Yeah, so, dapagliflozin is a drug,
so called SGL2 inhibitor. These were drugs developed
for the treatment of type two diabetes. And they were developed in
the setting of FDA guidance on the development of diabetes agents. Where we knew that they lower blood sugar, we knew that they help
control hemoglobin A1C. What we don’t know is how safe they are. And as you know well,
there have been a series of diabetic drugs which raise
the risk of cardiac disease. Cardiac events. And so, the FDA a number of years ago put into place large scale studies to really demonstrate that
the drugs were not only good at improving blood sugar, but cardiac risk, could
they understand it? So a number of large trials were done and with the SGL2 inhibitors,
something interesting emerged. Not only might there be benefit, or lack of harm,
of the SGL2 inhibitors, there may actually be cardiac benefit. That’s a profound statement. And we didn’t expect that at the outset. – This is fascinating
because when you think about the biology of
actually where the SGLT2 is, that cardiovascular effect
might not be cardiac specific. – That’s correct, that’s correct. And it may not be diabetes specific. – You got it. – And that was the interesting
thing about DAPA HF is that they took a group of
patients with heart failure, many of whom had diabetes, but not all. And they were really looking to say with this diabetes treatment, could you improve
outcome in heart failure? Wow. That’s kind of a bold question. – And that is an important question. – A really important question, and really makes the case
for the power of observation, is to really keep in mind, as you said, the biology, the mechanism, and think about not just the
fact that it lowers blood sugar but might it have other
benefits in patients with cardiovascular disease,
in this case heart failure? And I would say, Ivor,
this trial was a home run. They demonstrated that
there was a big reduction in the combination of heart
failure hospitalization or mortality, and there
was an effect on mortality. Which we don’t often see in these trials. And this was on top of
aggressive medical therapy for heart failure, with
things like ACE inhibitors and beta blockers, widely used. – And obviously, this family of drugs also have implications,
not only for cardiac events but even hospitalizations. And when you think overall, cost of just managing patients with chronic heart failure. – Yeah, I think that’s well said, is we think about the
whole, quality of life, cost effectiveness, clinical outcomes, in this particular trial,
it all fits together nicely. And I think that it was
an exciting trial result. It’s being shared widely
with the world today. And this is something that I’m sure that people will want to read the papers, when they come out, with great interest. – You know, Bob, this speaks eloquently to what you just now mentioned. It was observations in the laboratory. That then obviously evolved
into new therapeutics that actually have real world benefits. Especially when you think about
the burden of heart failure. Not only in the United
States, but globally. It’s quite substantial. And to really have drugs that can be considered game changers in the management of patients who have systemic diseases,
multi-system disease, not to mention, of course,
additional populations who may have, for example, renal disease. – Yeah, and this one in
particular was fascinating because here’s a anti-diabetic agent, you say, okay, it improves
heart failure outcomes in patients with diabetes, I get that. No no no, it improves the outcomes in patients both with and without diabetes and that to me, is fascinating. – It absolutely is. Bob and I obviously can
keep going on reporting here from ESC 2019, but thank you so much, Bob, and we look forward to additional studies that might be coming
along at these meetings. – I look forward to talking
with you again, Ivor. – You will.

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