Preview Mode Links will not work in preview mode

Circulation on the Run

Dec 31, 2018

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.