INTERVIEW
Who has HFpEF?
Review of Trials Finds
Inconsistent Answers
This year, there have been landmark clinical
trials that have left cardiologists with some major
therapeutic advances for patients with heart failure and reduced ejection fraction. But there have
been less advances for neuro-hormonal modulation device therapy in terms of heart failure
with preserved ejection fraction or HFpEF, and
specifically the inclusion criteria of trial subjects.
CSWN spoke with Jacob Kelly, MD, a fellow of
cardiovascular disease at Duke University Medical Center, and first author of a state-of the-art
review, published in a recent issue of JACC, “Patient Selection and Heart Failure with Reserved
Ejection Fraction.”
CardioSource WorldNews: It’s an interest-
have to figure out how you are going to decide
if that worked or not. So by looking at the
methodology of selecting patients in previous
clinical trials and by looking at their successes
and/or failures, you can then decide what’s been
helpful, use those lessons, learn from them, and
design future trials that can best evaluate if a
therapy (such as LCZ of the recent PARADIGM
trial that’s been so successful in HFrEF) may
be beneficial in HFpEF. But if you do the trial
wrong and you get intermediate values, you may
not have a conclusive answer. So that’s why the
methodology is so important. You have to select
your patients appropriately, and that’s what we
try to understan d in this review and discuss with
our readers and our clinicians.
perhaps a device—and then you need to mesh
the things together. By looking a little bit at prior
trials, looking at those patient-selection criteria
that drove event rates, you can get an idea of how
to power your study and how to select patients
so that you have your best chance of determining
if that test, that therapy is helpful for our
patients, which is really what we want. We want
to improve the lives of our patients.
And what you found is that it varies.
You need to take this group of thought leaders in
the field and see what they’ve said about previous
trials—critically appraise and think about it, and
see where things have been successful. What
we found, just on our review—and this is what
we suggest, and you can see that from the trial
evolution from previous to current—that by using
higher levels of EF, you’re selecting for a more
true HFpEF versus a HFrEF population by using
elevated levels of naturetic peptide levels, even
higher perhaps in patients with co-morbidities,
which are very common and very important in
HFpEF, such as atrial fibrillation; you can select
for specificity of HFpEF. Then look at how the
patient’s prior history of heart failure is defined,
and how they are being defined now. Sometimes
you need to use things like hemodynamics
or stress testing to really confirm that HFpEF
is HFpEF. Using this whole milieu of patient
selection criteria and looking at where they have
driven event rates and prior trials is how you
can successfully define a trial that’s going to be
successful for your therapy at play.
ing story. Tell us about the paper first.
Jacob Kelly, MD: Thank you so
much for this opportunity to represent Duke University and Global Cardiovascular Clinical Trialists—and
all my colleagues who helped with
Jacob Kelly, MD
this paper. Review papers are kind of
an interesting animal in that you’re
trying to look at all the available evidence and to
talk to your audience. So I think it’s important
to understand this process. Specifically, for this
paper, it focused on the discussions between an
important group of folks from the global cardiovascular clinical trial list that’s been forming for
10 years. That’s led by Faiez Zannad, MD, and
Bertram Pitt, MD, and it brings together clinician scientists, clinical trialists, regulators from
Europe, all around the world, the United States.
I think what they do is to critically appraise very
recent—and even compared to older trials—to
discuss how we can build future clinical trials that are actually successful at treating our
patients.
Why is it important to better understand the
methodologies used in these HFpEF trials?
That’s a great question. When you think about
how a clinical trial is built you need to identify
your patients, you need to identify a therapy
that may be benefitting these patients, and you
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CardioSource WorldNews
Absolutely. I think it’s important to understand
your patient population. You look at the patients
whom you want to study. You look at the
intervention or the therapy—be that a drug or
By looking at the
methodology of
selecting patients
in previous clinical
trials and looking at
their successes and/
or failures, you can
then decide what’s
been helpful, use
those lessons, learn
from them, and design
future trials.
You had to wrap your mind around the fact
that you’ve got guideline definitions of HFpEF, you have clinical trial definitions, and
you have cut points used to indicate HFpEF
that can vary—you had some real challenges
here. What did you find when you put it all
together?
It’s largely subjective in terms of where we
are right now. You’re hoping to make that a
little less subjective.
I think that’s the future. We still have to focus on
Continued on page 45
October 2015