Hello, everyone. My name is John Jarcho. I'm a deputy editor at the New England
Journal of Medicine, and I'm very happy to be here on the floor of the meeting
of the European Society of Cardiology here in Paris, France. I'd like to talk to
you for a few minutes about some of the interesting trials that the New England
Journal of Medicine is publishing online simultaneously with the presentations of
the papers here at the meeting. One of the interesting trials that was
presented here yesterday is a trial called the COMPLETE trial, which was a
trial that evaluated the question of whether patients who are undergoing
primary PCI for an acute ST-elevation myocardial infarction should also have
revascularization of significant non-culprit lesions that are found in other
coronary arteries during the catheterization procedure. There have
been a number of previous smaller trials that have demonstrated that there
probably is a benefit in this setting to revascularizing non-culprit lesions, but
those trials were sufficiently small that the evidence that they were able to
gather really rested on the ability to prevent subsequent revascularisation
procedures, and no trial had been large enough to this time to evaluate the
question using hard clinical endpoints of cardiovascular death or myocardial
infarction. The COMPLETE trial, which was much larger than previous clinical
trials in this space, was designed to do exactly that. Patients who are undergoing
primary PCI for ST elevation myocardial infarction were randomized to two groups:
one group was to undergo non-culprit lesion revascularization
to be performed at a subsequent procedure to the main procedure at the
time of the original catheterization. The other group was randomized to undergo no
further revascularisation unless they developed clear-cut manifestations of
cardiac ischemia or other cardiac events. The trial had two co-primary outcomes, one
being cardiovascular death or myocardial infarction; the other being
cardiovascular death, myocardial infarction, or urgent target
vessel revascularization, and the trial successfully demonstrated a significant
benefit on both of these co-primary outcomes, thus indicating that it is
desirable to revascularize non-culprit lesions, the only proviso being that it
should not be done in the same setting as the original PCI, since that
was not tested in this trial. It did appear in the trial that it didn't make
any difference whether the second revascularization procedure was
performed during the same hospitalization or on a subsequent
hospitalization later on. A second trial of great interest and one that was very
highly awaited was the PARAGON-HF trial. The PARAGON-HF trial was a trial
conducted in patients with heart failure with preserved ejection fraction to
evaluate the potential benefits of sacubitril-valsartan in such
patients. Sacubitril-valsartan has already been shown to be beneficial in
patients with heart failure with a reduced ejection fraction,
and it was hoped that there might be benefit in patients with heart failure
with preserved ejection fraction as well. This is a difficult patient population,
one in which a number of promising therapies have been found not to be
beneficial, and the hope was that this trial would be different. Patients were
randomized to either sacubitril-valsartan or to valsartan alone. They
initially went through two screening periods during run in, for which they
were tried with first valsartan, and then sacubitril-valsartan,
to be certain that they had reasonable tolerance to both
medications. Provided that was the case, they were randomized in the trial. The
primary outcome of the trial was total heart failure hospitalizations and
cardiovascular death, a composite outcome which allowed more than one endpoint per
patient, and which required special statistical methodology to analyze. The
result, disappointingly, was that again in this trial there was not a statistically
significant benefit of sacubitril-valsartan compared to valsartan
alone in this patient population. There were some findings in secondary outcomes
which did suggest the possibility that there might be some degree of benefit in
this group, if you look at things such as New York Heart Association
classification and Kansas City cardiomyopathy score,
but in the absence of a significant benefit on the primary outcome these
findings have to be taken with some caution. In addition, there was an
interesting finding on subgroup analysis that suggested that patients on the
lower end of the ejection fraction range might benefit from this treatment,
whereas patients on the higher end of the ejection fraction range did not, thus
suggesting that the patients in the original PARADIGM-HF trial, with an
ejection fraction of less than 40% who benefited, that there might also be
benefit above that ejection fraction range up to the range of perhaps 50% or
so; thus, in patients who had not truly
reduced, but not quite normal, ejection fraction. A third trial which
was presented today and which had unexpected results was the ISAR-
REACT 5 trial. This was an interesting trial that made a head-to-head
comparison of two antiplatelet agents, ticagrelor and prasugrel, to see
how these two drugs performed in patients who presented with an acute
coronary syndrome and who were undergoing percutaneous coronary
intervention. Both of these drugs have been separately compared to clopidogrel,
and found to be beneficial, but there has never been a very large head-to-head
comparison of the two drugs. Some smaller head-to-head studies had been
inconclusive. The authors anticipated that they would find that ticagrelor
was superior to prasugrel for the composite outcome of cardiovascular
death, stroke, or myocardial infarction. To their surprise they found the reverse:
they actually found that prasugrel was superior to ticagrelor.
With regard to safety, the two drugs were compared for the endpoint of major
bleeding, and it was found that there was no significant difference between the
groups. Thus suggesting, against the original anticipations of the
investigators, that prasugrel may, in fact, be the preferred drug in this
clinical setting. These are just some of the major clinical trials that the New
England Journal has published online to coincide with presentations at the
meeting of the European Society of Cardiology. For full details of these
trials, and for other papers that we have published with the meeting, please
consult our website, www.NEJM.org. Thank you.