Circulation January 2, 2019 Issue

Dr Carolyn
Lam:                               
Welcome to Circulation on the run, your weekly podcast summary
and back stage pass to the journal and its editors, and welcome
to a whole new podcast format in 2019. Ha-ha, I bet that
surprised you. Well guess what? This new format promises more
interaction, more discussion and a whole lot more fun, and that's
because to begin with, you don't have to listen to me talk to
myself half the time anymore. I'm Dr Carolyn Lam, associate
editor from the National Heart Center and Duke National
University of Singapore, and I am simply delighted that Santa
gave me a partner on this podcast, and co-hosted with me, and my
gift is none other than Dr Greg Hundley, associate editor from
the Pauley Heart Center, at Virginia Commonwealth University
Health Sciences. Welcome Greg.


Dr Gregory
Hundley:                      
Thank you so much Carolyn. How exciting is it to start this new
year with this exciting format, where we'll take several of the
key manuscripts from Circulation and discuss them? Picking five
each time, and as you've alluded to, we're not going to get rid
of that favorite format, where we take a select paper and
interview and work with the authors.


Dr Carolyn
Lam:                               
Exactly. In fact, maybe I could liken it to welcoming everyone to
join us over a cup of coffee, each week, with the journal in the
hand and we're just going to discuss it, and never forgetting
that feature paper with the authors, and this week's paper is
huge. I love it. We're actually going to be talking about blood
pressure control in the barber shop. But before then, here's the
articles that we've chosen to discuss. So Greg, you got your
coffee ready? Shall we start?


Dr Gregory
Hundley:                      
Absolutely Carolyn, and let's get going first with Gorav Ailwadi,
from University of Virginia, his paper evaluating the utility of
MitraClips in those with secondary mitral regurgitation. This is
really a follow-up from the EVEREST study. It's not a randomized
trial, but it's a longitudinal look over time, at 616 patients.
Interestingly, those individuals that had class three or four
heart failure, that had the MitraClip, the left ventricular
volumes got smaller in a year, the hazard ratio for events became
less. The magnitude of mitral regurgitation went from 4+ down to
2+. Exciting findings.


Dr Carolyn
Lam:                               
Interesting, but you know Greg, these all sound so positive. Why
is it so different in the Mitra FR study?



 


Dr Gregory
Hundley:                      
Absolutely Carolyn. So, as you know, Mitra FR, that was a
randomized trial. So, this study doesn't compare, the EVEREST
study in this issue, doesn't compare with conventional medical
therapy, that's number one, and Mitra FR did. Also, the Mitra FR
patients were a little bit sicker. The ejection fraction really
was 15 to 40 percent, and in the EVEREST study, much higher,
average 45 percent. In fact, many had a normal EF. So it really
raises a lot of questions as to whether or not this finding will
hold up in future randomized trials, which we'll be looking to
see the results.


Dr Carolyn
Lam:                               
Indeed, and it was really nicely discussing the accompanying
editorial wasn't it, which I really enjoyed. Well, the paper I
picked out Greg is from Dr Gatzoulis from The Royal Brompton
Hospital, and it's actually the MAESTRO trial. Now, MAESTRO is a
randomized control trial of the endothelin receptor antagonist
macitentan in patients with Eisenmenger syndrome. Short and long
of it, macitentan did not show superiority over placebo on the
primary endpoint of change in baseline to week 16 in exercise
capacity. And there was also no relevant trends observed for the
secondary endpoints.


                                                               
However, among the exploratory endpoints, macitentan did reduce
Nt-proBNP in the main cohort, and improved pulmonary vascular
resistant index, and exercise capacity, in a hemodynamic
sub-study. Importantly also, there were no specific safety
concerns with macitentan.


Dr Gregory
Hundley:                      
Sounds really interesting, Carolyn. But how did this compare with
prior studies that have really focused on endothelin?


Dr Carolyn
Lam:                               
Great question. So, MAESTRO's only the second randomized control
trial of an endothelin receptor antagonist in Eisenmenger
Syndrome. BREATHE-5 was the first, and this used a different
endothelin receptor antagonist that was bosentan, also in
Eisenmenger Syndrome, and actually found that bosentan reduced
pulmonary vascular resistance as its primary efficacy endpoint,
without worsening systemic pulse of symmetry.


                                                               
So, very different trials in terms of endpoints, as you can hear,
but also importantly, different populations that were enrolled.
MAESTRO enrolled a more heterogeneous population with more
complex forms of Eisenmenger, including patients with Down
syndrome, had a broader WHO functional class inclusion, and
allowed the use of pre-existing therapies such as PDE5
inhibitors.



 


Dr Gregory
Hundley:                      
That's really spectacular, Carolyn. Very interesting findings for
something that these vasoconstrictors, vasodilators, often very
harmful. Switching over, I've got sort of another paper that is
also working on vasodilation, but comes really from the world of
basic science. And it's from Ingrid Fleming from Goethe
University in Frankfurt, Germany, examining how does hydrogen
sulfide, a common gas that we have in the environment, it smells
terrible, we worry about sulfuric acid and acid rain, but how
does this promote vasodilation in the system?


                                                               
And so, in this basic science study, they unlocked sort of a key
that this hydrogen sulfide is produced by cystathionine
gamma-lyase, CSE. And why is that important, and what does it do?
Well, production of H2S by CSE goes and inhibits human antigen R,
or HuR, that regulates cellular proliferation and growth. And so,
basically these authors have unlocked a mechanism by which
hydrogen sulfide can be protective.


                                                               
So, what's interesting Carolyn is that patients can have elevated
levels of L-cysteine, increased expression of CSE, so you've got
the components and the manufacturer of H2S, but they still have
low arterial levels.


Dr Carolyn Lam:
               
               
Hm. So, how can this be addressed then? How can we raise that
H2S?


Dr Gregory
Hundley:                      
That's what's so clever that the investigators found out,
Carolyn. They found a slow-release oral active drug, a sulfide
donor called sodium polysulthionate, H2R, or sulfhydration, and
can inhibit atherosclerosis development or progression when these
levels are low.


Dr Carolyn
Lam:                               
Indeed. sodium polysulthionate. Awesome, Greg! That is so cool.
Honestly I just loved your explanation of that. Okay. Well, I've
got another paper to share. And this is from Dr Bress and
colleagues from University of Utah School of Medicine. And this
one is really interesting because these authors estimated the
number of cardiovascular disease events that could be prevented,
and the treatment-related serious adverse events that could occur
over ten years, if U.S. adults with hypertension were achieving
the 2017 ACC/AHA guideline recommended BP goals, compared to
their current blood pressure levels, as well as compared to
achieving the older 2003 JNC7 goals, or the older 2014 JNC8
goals.


                                                               
Now, basically they found that achieving and maintaining the 2017
guideline blood pressure goals over ten years could prevent three
million cardiovascular disease events, a greater number of events
prevented compared to prior guidelines, but this could also lead
to 3.3 million more treatment-related serious adverse events.


Dr Gregory
Hundley:                      
So, Carolyn, hasn't a main concern of this type of work been that
these new guidelines over-extend the reach of our treatment?


Dr Carolyn
Lam:                               
That's a real concern that I've also heard. The lower blood
pressure thresholds used to define hypertension in the 2017
guidelines could indeed lead to more diagnoses. However, this
paper helped because remember that the recommendation for
anti-hypertensive drug treatment in patients with the
pre-treatment blood pressure of 130-139 systolic, or 80-89
diastolic, was limited to those at high cardiovascular disease
risk. So not everyone, but only those at high cardiovascular
disease risk.


                                                               
And so, treatment under the 2017 guidelines, by these data, would
lead to more health gains, while only extending treatment to 5.4%
more adults with hypertension compared to JNC7. So, this paper
really modeled these things out with important contemporary U.S.
adult populations using a national representative, a sample of
U.S. adults, and NHANES, as well as REGARDS, and they also used
estimates of benefit from the recent large meta-analysis of 42
blood pressure-lowering trials.


                                                               
So, important data that I think are going to be reassuring to a
lot of people managing these patients. Well Greg, that really
brings us to the end of our little chat. Now, let's move to our
future discussion, shall we?


                                                               
Could cutting blood pressure in a barber shop be the long-term
solution to hypertension in African-American men? Well, the
future paper of this first issue in 2019 really talks about it.
Greg and I are so delighted to have with us the authors of the
paper, Dr Ciantel Blyler, and Dr Florian Rader from Cedars-Sinai
Medical Center, as well as our associate editor, Dr Wanpen
Vongpatanasin.


                               
                               
So, Ciantel, can you just perhaps start by telling us what you
found.


Dr Ciantel
Blyler:                              
So, what we're talking about today are the 12-month results as a
follow-up to our 6-month results that we published earlier this
year. So, we took 319 African-American men in Los Angeles County,
and randomized them to two groups. One group saw a clinical
pharmacist who worked with them to reduce their blood pressure,
and the other group just worked with their barber to talk about
blood pressure, and encourage usual follow-up.


                                                               
And, as we saw at the 6-month mark, blood pressure really
improved in the group that was able to work with the clinical
pharmacist. So, we saw an almost 29 mm Hg drop in the
intervention group, as compared to only 7 mm Hg in the control
group.


Dr Gregory
Hundley:                      
Ciantel, Florian, that is really exciting results. What is a
collaborative practice arrangement, and how did you affect that
in Los Angeles?


Dr Ciantel
Blyler:                              
So, collaborative practice is actually widespread in the United
States. California is one particular state that is kind of ahead
of the curve with respect to collaborative practice between
pharmacists and physicians. But what it essentially allows a
pharmacist to do is to prescribe, monitor, and adjust medications
underneath a physician's supervision. So, a document is drawn up,
medications are selected, and an algorithm so to speak is put
together so that a pharmacist can treat a patient independently
of a physician needing to be there.


Dr Greg
Hundley:                            
Very nice. And did you find in the pharmacist-led group that
these patients were taking a different anti-hypertensive regimen,
or were they more compliant? What do you think was the reason for
the discrepancy in this magnificent blood pressure drop in this
group of hypertensive men?


Dr Florian
Rader:                             
So clearly, there were a lot of differences between the two
groups. First of all, we had a protocol with our favorite blood
pressure medications that we use clinically here in the
hypertension center at Cedars-Sinai. Essentially it is
long-acting calcium channel blocker, specifically Amlodipine,
longer-acting angiotensin receptor blockers, or ACE inhibitors,
and a third line, usually a thiazide diuretic, and also a
longer-acting one, not the usual Hydrochlorothiazide, but
specifically Indapamide that we used for this research study.


Dr Greg
Hundley:                            
And do you think that there was more compliance in this
pharmacist-led group?


Dr Florian
Rader:                             
One would expect that. First of all, I think that seeing the
clinical pharmacist, more frequently being reminded of taking the
medications, having feedback by actually seeing the blood
pressure numbers in the barber shop, I think would help. But
then, in addition, we choose these medications not only because
they affect it, but also because they're easy to take. They're
once-a-day medications with very high continuation rates in
larger studies, so they're just easier to take than other
medications that are oftentimes prescribed.


Dr Greg
Hundley:                            
It sounds like also, there might have been a trust factor.
Because you're seeing the same person over and over in a very
nice environment. Was that a factor?



 


Dr Ciantel
Blyler:                              
Absolutely. I think there's a different level of trust that's
established when you meet somebody on their own turf. So I think
the fact that we met men in barber shops where they felt
comfortable, where many of them had been going to the same barber
for over a decade, it made all the difference in terms of
establishing a rapport, and gaining their trust with respect to
having them take medications. So, I think that was a huge part of
why we saw increased adherence, and really sort of a commitment
to the program.


Dr Greg
Hundley:                            
And we certainly recognize how harmful hypertension is in
individuals of Black race. How does this group in Los Angeles
translate to perhaps other Black men in the United States?
Particularly, for example, in the South.


Dr Ciantel
Blyler:                              
I think the program could translate really anywhere. I think what
makes it so tailored to African-American men is this notion of
going into a barber shop, which is a very important place in the
Black community. So, again, sort of going back to what I said
earlier, most of these men had been seeing the same barber as
frequently as almost every two weeks for over a decade. So, it
really helps increase the frequency with which we could interact
with the men, and it helped with continued follow-up and
adherence to the program.


                               
               
               
With respect to the area of the country again, I think it
translates.


Dr Carolyn
Lam:                               
I've got a follow-up question to that, if you don't mind. So, I'm
here listening all the way from Singapore, and I'm just so
impressed, and frankly just enamored by this study. And wondering
what is the barber shop to my local Chinese guy? I'm actually
wondering if it's the kafei dian and that stands for coffee shop,
and I'm also wondering what about the women? Wanpen, do you have
any insights that you want to share?


Dr Wanpen
Vongpatanasin:         I
believe that even Dr Victor had thought about the beauty shops,
that is a barber shop study in parallel, and this could very well
work very well. Who knows, we could be going to massage parlor,
anywhere, that when we feel relaxed and be ourselves, we go out
our way, out of our regular activity, and it could really be a
neat idea. And for a study, I'm not sure I could do something out
of the box. I would say it must have been successful as this
approach, and partly it could be because of the additional
pharmacists engage likely. So, I think this is a perfect
combination.


Dr Greg
Hundley:                            
Wanpen, you had mentioned Ron Victor. Maybe Ciantel, Florian, and
Wanpen, you used to work with him. What did Ron mean to this
study? Ron Victor unfortunately passed away this past Fall.


Dr Florian
Rader:                             
Ron hired me almost seven years ago now straight out of
fellowship. He was personally my mentor. He taught me all the
tricks when it comes to the work of the management of
hypertension, so personally I owe him a lot. Regarding the study,
he's been thinking about this for a long time, this approach to
hypertension management. He's tried it in Dallas. It worked
partially, but not very well because he didn't have a pharmacist,
and he didn't have somebody that made it their goal to lower
blood pressure no matter what.


                                                               
And in this study, we had somebody like that, the clinical
pharmacist. So, Ron Victor has thought about this for a long
time, has done a lot of analysis of the Dallas hypertension
study, and figured out why it didn't work out in Dallas, and
really cooked up a recipe for this trial, and the results speak
for themselves.


Dr Greg
Hundley:                            
Wanpen, do you have anything to add about Ron? I think he was
your mentor as well.


Dr Wanpen
Vongpatanasin:        
Absolutely. I trained with him actually from the internship until
fellowship, and I owe my career to him. And actually, I see this
idea stemming from the Dallas heart study when he did the survey,
and realized that if you just wait for patients to show up in the
clinic, that you're not going to get anywhere, because African
Americans have higher blood pressure at a younger age, and are
more susceptible for target organ damage. And as we all know, by
the time many presented with, they already have end-stage kidney
disease or cardiovascular disease by the time first presentation.
So, to avoid it, we have to go into much earlier, not wait until
they come to the healthcare facility, and I'm glad to see that
this idea is really becoming widely successful more than anyone
can imagine.


Dr Carolyn
Lam:                               
What a beautiful tribute. What a poignant note. Thank you, all of
you, for your great input, and for publishing this amazing paper
with us at Circulation!


                                                               
Thank you, listeners, for joining us today on Circulation on the
Run with Greg Huntley and me. Thank you, and don't forget to tune
in again next week.


                               
                               
This program is copyright American Heart Association 2019.