Dec 19, 2023
Dr. Raymond Benza, a Professor of Medicine at the Icahn School of Medicine at Mount Sinai, discusses dual therapy in the treatment of pulmonary hypertension (PH) through the concept of risk stratification.
Good
day everyone. My name is Dr. Raymond Benza. I am a Professor of
Medicine at the Icahn School of Medicine at Mount Sinai in New
York. I am a Pulmonary Hypertension physician and researcher in
risk stratification and genomics of the disease. Today, we're here
to speak about the concept of dual therapy.
Now, the importance of dual therapy, I think, has been conceived in
looking at the data and looking at the outcome of patients who have
been treated with monotherapy versus dual therapy. This has evolved
using the concepts of risk stratification. As we know, risk
stratification is now one of the most important ways in which we
judge the severity of disease and then try to match the
aggressiveness of our medical therapy based on that level of
risk.
Three main risk groups exist commonly, low, intermediate, and high
risk. These are all based on mortality estimates. With a low-risk
patient expected to experience a mortality rate of only 5% per
year. An intermediate risk patient expected to experience a
mortality of rate between five to 10%, and then a high-risk patient
expected to have a mortality rate in excess of 10%. We use this
risk stratification allocation, which are based on several
multiparametric algorithms or formulas based on very common
variables that we assess clinically; including functional class or
natriuretic peptide levels, six-minute walk distance, and some
imaging, and hemodynamic variables.
We use these to classify our patient's risk before we start
therapy. What we have found is that patients even deemed low risk,
seem to do better with two upfront drugs as opposed to one upfront
drug. This is a very important concept, because as many of you
remember about a decade ago, we would start medication
serially.
We would try one drug and then if the expected functional
improvements didn't match what we wanted, we would add a second
drug and then wait a little bit and add a third drug. But we have
really changed the way that we do that now based on these risk
stratification schemes. So upfront patient treated initially would
be with two drugs of different classes, most often an Endothelin
Antagonist and a PDE5 inhibitor, irregardless of whether they were
low or intermediate risk.
Patients who are higher risk would be treated with upfront triple
therapy. So an Endothelin Antagonist, a PDE5 inhibitor, and
prostacyclin analog. Using these upfront combination therapies, we
have found that the outcome of patients have improved significantly
within each one of those risk categories. That's not to say that
patients who are low risk may not benefit from starting one
therapy. In fact, there's been a recent study that was published a
month or two ago in the CHEST Journal that demonstrated that people
at ultra-low risk usually indicated by a REVEAL score of less than
five can continue to benefit from monotherapy. This has not been
translated into the guidelines yet.
So at this point, any low-risk patient according to the guidelines,
to still get an upfront dual combination therapy in order to give
them the maximum benefit to achieve low risk and to maintain low
risk. That's our main concept now in our follow-up for patients
with pulmonary hypertension. Usually at three-to-four-month
markers, we will take a look at a patient in totality and calculate
their risk scores. Again, either using the US system REVEAL or the
European system, to see where they are in that risk continuum.
If patients continue to be at intermediate or higher risk is when
we will add additional therapeutics to their regimens. Perhaps
switching a PDE5 to riociguat or adding a prostacyclin analog, or
titrating a prostacyclin analog. Even if they're on triple therapy,
we may start considering whether they may be eligible for
transplantation or not, or if any of our new experimental protocols
that come out with some new compounds.
That's the good news for PH patients at this point, is that we have
a lot of new drugs in the pipeline to treat this disease that
really work on the disease in a different perspective than our
older medications do. They really are now geared towards making the
pulmonary vessels normal again, so not dilating them, but actually
working on the meat of the vessel to make that vessel thinner and
more compliant.
I think that's really captures the essence of the use of upfront
combination therapy or dual therapy. Now, again, is to drive
patients even at the lower ends of risk to the lowest risk
possible, to give them the best mortality and morbidity
expectations over the subsequent year with the caveat that frequent
reassessments of patients is required and frequent adjustments of
medications to keep them or to achieve low risk is indicated.
As always, thanks for listening. My name is Dr. Raymond Benza and
I'm aware that my patients are rare.
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