Health inequity is among the most glaring issues in the US healthcare system. And now, the 

 pandemic has taken a magnifying glass to the issue.

A recent update from the US Centers for Disease Control and Prevention (CDC) 

 showed that 45% of observed COVID-19 patients for whom race or ethnicity data was available were white, compared to 55% of individuals in their surrounding community. 

However, one-third of all hospitalized patients were black, versus just 18% in the community. Another 8% of hospitalized patients were Hispanic, compared to 14% in the community. Minorities are over-representing the population of COVID-19 patients in hospitals right now.

Death rates are also more severe for Black and Hispanic patients—almost double the rate of white or Asian patients to die from COVID-19 per 100,000 population.

In the most recent DocTalk podcast interview, Panagis Galatsatos, MD, MHS, of Johns Hopkins School of Medicine, joined HCPLive to discuss the underlying effect of health disparity in the US, how the COVID-19 severity inequity could burden differing populations, and what large-scale solutions might better access to care and clinical monitoring of disease.

Galatsatos also explained why metrics including the above CDC data doesn’t shock him and his colleagues.

“For those of us who study health equity, it’s not a shock, but it is an ethical reckoning,” he said. “What to make of this, for a lot of us, is, ‘welcome to the conversation.’ We’ve been having it for decades, and a pandemic will sure as heck shine a light on these issues that we’ve been screaming about constantly.”

Podcasts

Panagis Galiatsatos, MD, MHS, joins to discuss the underlying issues and potential solutions to COVID-19 patient disparities.

DocTalk Podcast: COVID-19 Health Inequity

“Even in our own healthcare system, it’s something we’ve talked about for years,” Albert Rizzo, MD, said. “And within a matter of weeks, we’ve ramped up the virtual systems in our practice.”

Rizzo, the chief medicine officer of the American Lung Association (ALA), was discussing the sudden and critical application of telehealth measures to respiratory clinics following the spread of 

. But he may as well have been talking about overall public health preparedness measures: a viral pandemic of this extent is unprecedented in modern history, and public health relied on years of rhetoric to enact decisions needed within a moment’s time.

Now, a month removed since the first major actions to prevent COVID-19 spread were set in the US, Rizzo joined the 

 DocTalk podcast to discuss the tiers of clinical impact the pandemic has had on 

From understanding differences between COVID-19 and respiratory disease symptoms, to the implementation of telehealth practice, to explanation as to why—despite its overall burden on health&mdash;now may not be the best time for a patient to attempt in quitting cigarettes, Rizzo detailed the landscape of pulmonology practice and research during the coronavirus.

“There’s certainly a lot of unknowns regarding the therapies being utilized now in the hospitals,” he said.

Al Rizzo, MD, of the American Lung Association, discusses some of the biggest challenges and questions raised on lung health during the coronavirus pandemic.

DocTalk Podcast: Respiratory Health During COVID-19

 event was once accompanied by incredibly grim prognosis, endless hours of research and clinical work have resulted in drastic improvements in post-stroke care, as well as primary and secondary prevention.

Though research in stroke care headlines both neurology and cardiology conferences throughout the year, the ASA International Stroke Conference (ISC) 2020 offered perhaps the most comprehensive view possible of advances in stroke in recent decades.

, the conference showcased years of research from the leaders in stroke research and care from throughout the world.

One of those leaders was Ralph Sacco, MD, chairman of the Department of Neurology and Olemberg Family Chair in Neurological Disorders Miller Professor of Neurology at the University of Miami, who was announced as the next Editor-in-Chief of 

editorial team caught up with Sacco via phone after ISC 2020 to discuss his biggest takeaways from the conference and what he is most excited about when looking ahead to the next decade of stroke care.

The incoming Editor-in-Chief of Stroke discusses what the future of stroke care might look like and his biggest takeaways from ISC 2020. 

DocTalk Podcast with Dr. Sacco: Future of Stroke Care and ISC 2020 Review

While almost every field in medicine has grown by leaps and bounds in recent decades, this statement may be most true when discussing progress made in 

The strides made in recent years have been noticeable on multiple fronts. From education to awareness to research and development of new therapies, the field of rare disease is in the midst of a massive push forward and it appears it will remain that way for the foreseeable future.

A countless number of people have seen the benefit and been impacted by this change in the field, but just as many have contributed time and effort into growing awareness and educating about rare diseases. Patient advocacy and awareness groups are paramount when discussing any serious condition, but those in the rare disease space have gone above and beyond in recent years—setting a new standard for outreach and impact.

One of the many groups involved in promoting rare disease is the National Organization for Rare Disorders (NORD). Founded in 1983 with the goal of providing support for those affected by rare disease as well as advocating and funding research in rare disease.

invited Sika Dunyoh, director of education programs with NORD, to take part in a special Rare Disease Day edition of the DocTalk Podcast. While every member of NORD has an important position that contributes to ever-increasing awareness and concern for individuals with rare disease, 

wanted to learn more about how outreach and education has impacted the space.

In this episode of the DocTalk Podcast, Dunyoh discusses changes in the field, significant moments from the past year, overlooked areas of research, and how education programs from the organization will continue to push progress forward.

Sika Dunyoh, director of education programs with NORD, discusses that year in rare disease and what to expect moving forward. 

DocTalk Podcast: Rare Disease Day 2020

With approval as an adjunct to maximally tolerated statin therapy for the treatment of adults with

 heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease

, bempedoic acid has the potential to transform treatment algorithms.

Backed by the phase 3 CLEAR program, which included 4 trials used in support of 

, the therapy sports an undeniably strong clinical profile—indicating treatment could result in reductions of LDL-C as high as 18%. The first-in-class therapy was also at the center of an analysis presented at AHA 2019 that found could also help improve on-HDL-C, total cholesterol, apolipoprotein B, and hsCRP from 12 weeks of treatment.

However, as with every approval, the prescribing practices in a real-world setting may be different from those in a clinical trial. Creating questions that may go unanswered by labeling information.

reached out to Christie Ballantyne, MD, chief of Cardiology at Baylor College of Medicine and chair of the steering committee for bempedoic acid, to take part in a special FDA approval edition of the DocTalk Podcast and discuss how to effectively prescribe bempedoic acid in a real-world setting.

Editor's note: This podcast was recorded before the FDA announced the approval of bempedoic acid and ezetimibe and, as such, is not discussed in the context of use in a clinical setting in this recording. 

Hello, and welcome to this special FDA approval edition of the DocTalk Podcast. I'm Patrick Campbell, editor with HCPLive, and I'll be your host for today's edition of the show. Today we'll be talking with Dr. Ballantyne about the approval of bempedoic acid and where this drug fits into current regimens. 

First, I just like to start with you introducing yourself Dr. Ballantyne and then we can dive into some questions.

Hi, I'm Christie Ballantyne. I'm the Chief of Cardiology at Baylor College of Medicine in Houston, Texas. And I was the chair of the phase 3 lipid advisors for the bempedoic acid program.

Now, since bempedoic acid has been approved, I guess the first question is: how monumental is it that for the first time in decades, we have a non-statin option approved for lowering LDL-C, even as an adjunct?

Well, I think it's an important new option for both physicians and patients. Statins are fantastic drugs. They're highly effective. We have great data on them. But if we look at the 2 most common reasons people are seeing doctors or nurses or healthcare providers is basically high blood pressure and cholesterol.

Now, if we look at the way we treat blood pressure—we have lots of options. The average patient is pretty frequently on combination therapy. That's an older feel, but you know, we have many, many different options and different mechanisms of actions. So, you can work through and get people to their goals.

It's interesting if we take a look at the field of cholesterol, usually, people stop after option number 1. So, a lot of people are not being effectively treated. I think this is an important step to be able to offer our patients new options to help them get their LDL cholesterol is down to a zone that's more favorable.

Thank you for that. And, next, what does the ideal patient population for bempedoic acid look like? As with every drug, not every person that has the conditions it was approved for will see the same benefit that other people might. 

So, what does the ideal patient or bempedoic acid look like?

So, the first thing is that this is not going to replace statins as first-line therapy. Statins will remain the first-line therapy.

So, where this is used is if you have a high-risk patient and on maximally tolerated status, and they're still not where you want their LDL cholesterol to be. The approval specifically focuses on people who have documented atherosclerotic cardiovascular disease or people with familial hypercholesterolemia. That's a group that we know it's sometimes challenging to get their LDL cholesterol down to a desirable range.

And maximally tolerated statin varies from patient to patient. If a patient is able to tolerate a high dose of a high efficacy statin. Then very frequently, we don't need to add a second medication, but it happens that there are people who cannot tolerate these dosages or else they just have very, very high LDL or don't respond well and they need additional therapies.

Thank you for that. And as you touched on bempedoic acid was approved as an adjunct for lowering LDL-C. But some analyses of the 4 CLEAR trials found benefits and other areas as well, including HDL cholesterol, total cholesterol, and hsCRP. Can you dive a bit into the mechanism of ACL inhibitors and explain what this might mean in a clinical setting?

Right, so this drug inhibits ATP citrate lyase, and that's an enzyme that's important in the synthesis of cholesterol. It's a prodrug, it gets activated in the liver to the active form. So, specifically targeting liver production of cholesterol.

That's a similar mechanism to what statins do —they're also inhibiting cholesterol synthesis. It's a different enzyme HMG-coareductase, but they both end up lowering cholesterol in a cell and increasing LDL receptors. This is complementary to the mechanism of action, for example of ezetimibe that blocks cholesterol production or PCSK9 inhibitors.

So, what ends up happening is and what we're seeing from the CLEAR program is that the drugs—could be various options&mdash;combinations added together, and you reduced LDL cholesterol and that means you're going to also reduce total cholesterol.

What was interesting is the reduction in C-reactive protein. statins, which block cholesterol synthesis, reduce CRP and so does this agent. Some of the other therapies that work by different mechanisms PCSK9 inhibitors alone do not lower CRP, ezetimibe alone does not lower CRP. So, it seems to be something that's shared with the way a statin works.

Thanks for diving into that a bit deeper for us. And now from a patient perspective—1 of the if not the biggest question for any drug in this field&mdash;can we expect the effects to translate to a reduction in mortality and or serious events for patients? Is this lipid-lowering effect going to translate into something like that you think or is it too early to tell?

Well, in regard to this question, I think 1 of the reasons that the FDA approved this for the use of LDL lowering therapy is that levels of LDL cholesterol are a very strong surrogate marker for benefit. In other words, the FDA would approve drugs to lower LDL or that lower blood pressure and particularly if they understand the mechanism. The mechanism here is by basically upgrading LDL receptors, which is the same way that statins work, PCSK9 inhibitors, ezetimibe all work that way. They all do the same thing and they've all shown benefit.

So, we don't have outcomes trials yet, but we do have a considerable amount of data. Also, it's very important that there is a large outcomes trial in patients who are statin-intolerant that is already fully enrolled. So, we'll have that answer pretty soon, but I think we have sufficient data that someone can end up sitting, if I need further LDL reduction I have an agent, which has been studied in a lot of patients, it's shown that it's effective. It has a good safety profile and I have further data in the near future.

Thank you for that, and now just lastly, really quick, is there anything else that you think is important that clinicians should keep in mind when prescribing bempedoic acid to a patient in the real-world setting? I know we saw an increase in rates of hyperuricemia and tendon rupture in the studies. How do you approach that in a clinical setting?

So, 1 thing that's important. The first question is asking someone do they have a history of gout. People who had a history of gout in higher level of uric acid, those were the individuals who are most likely to have an increase in uric acid in they would also have an increased risk for gout.

That's important. Does someone have a history of gout and what is the level of uric acid. If they're taking allopurinol and the level is low, then you're fine. Then there are other individuals that may be at a high risk. So, it would not be unreasonable if you were concerned about someone getting a baseline level of uric acid. If it's high, you keep an eye on that.

The issue of tendon rupture—that this is 1 that I think we're going to need more data on. As we were doing the trials, it really wasn't very clear and 1 of the things that there was a 2:1 randomization. So, we had twice as many patients on the treatment as the placebo but obviously it's a warning. So, if someone is starting to have problems with a tendon and they're having some soreness or pain, it would be reasonable to stop the medicat

ion and then to follow the patient and see if things improved or not.

Okay, that was about it on my questions. Is there anything else you wanted to add about bempedoic acid?

Just 1 comment here. I think that bempedoic acid is a new option, but I think 1 of the things that's going to be happening is that in general, we will begin to treat lipids in a manner that's probably more similar to the way that we treat blood pressure. And with blood pressure we'd start with monotherapy, we quickly go to combination therapy—frequently have 2 medicines in 1 pill&mdash;and it's very common to actually have people who are on 3 medications in a high risk person where you're trying to blood pressure down to a low level.

That's going to be probably similar, I think to the future for a lot of people who are having difficult to treat LDL that we're going to use more combination therapy.

 All right, well, I just want to say before I let you go, thank you for taking part in the DocTalk Podcast, Dr. Ballantyne.

 Alright, that's it for this edition of the DocTalk Podcast. I'm Patrick Campbell, editor with HCPLive. Thank you for listening.

A discussion on how to approach the real-world application of bempedoic acid with the Chief of Cardiology at Baylor College of Medicine. 

DocTalk Podcast: Prescribing Bempedoic Acid with Christie Ballantyne, MD

Few advances in recent years have been as impactful and widely embraced as a standard of care as 

transcatheter aortic valve replacement (TAVR)

Less than a decade after its initial approval from the US Food and Drug Administration, the revolutionary therapy has completely changed the way cardiologists approach treatment of aortic stenosis.

Treating aortic stenosis treat once meant patients needed to undergo a surgical aortic valve replacement—requiring open-heart surgery, stopping the patient’s heart, and a lengthy inpatient recovery process. TAVR has revolutionized this process, and become first-line therapy for many patients with severe aortic stenosis. 

Instead of open-heart surgery, patients have an artificial valve placed in the aortic valve through the use of a catheter, typically placed in the chest or leg. Less than a decade after its approval, the procedure patients undergo can take less than an hour. Most are able to go home within a couple of days. 

In fall 2019, Tsuyoshi Kaneko, MD, cardiac surgeon at Brigham and Women’s Hospital and assistant professor of surgery at Harvard Medical School, took part in an episode of the DocTalk Podcast to give his perspective on TAVR and where he sees is progressing in the future. Since that episode, a slew of new data and studies have emerged offering greater insight into TAVR than ever before.

In this episode of the DocTalk Podcast, we discuss recent data from major medical journals to late-breaking sessions at the American Heart Association 2019 Scientific Sessions to find out what has changed and where he sees the role of the procedure as we learn more about the procedure and associated outcomes.

Hello, and welcome to the doc talk podcast. I'm your host, Patrick Campbell, editor with HCPLive, and today we'll be discussing TAVR with Dr. Tsuyoshi Kaneko, of Brigham and Women's Hospital. For our loyal listeners, you'll know that our very first episode featured Dr. Kaneko and we also discuss TAVR.

Now, we'll be discussing things that have happened in the last 6 months. So, I'd just like to say, Dr. Kaneko, welcome. If you could give our listeners a brief background on your experience then we can dive into our discussion.

: Sure, my name is Yoshi Kaneko and I go by Yoshi Kaneko. I am the surgical director of the structural heart program at the Brigham Women's Hospital and I'm also the director of outcomes research at our division as well. My expertise is in transcatheter work. I was trained in cardiac surgery and also in cardiology, so I do have the expertise and I actually practice both in my daily cases.

Thanks for that. And as I mentioned to our listeners, Dr. Kaneko, has joined us on the podcast before about six months ago to discuss TAVR. And just to start since we had our last discussion, AHA has occurred and more relevant studies have come out examining TAVR. In your opinion, what do you think is the most significant new data to emerge since the last time we spoke?

Patrick, I think the biggest change that we've had over the past 6 months, definitely we're still feeling the impact by the FDA to approve the low-risk patient for TAVR. I think that has that is the most single impactful thing that has happened because what that means is that right now, TAVR was approved for high-risk patients or patients who are not eligible for surgery, and then subsequently got approved for intermediate-risk patients.

Now it's approved for low-risk patients—meaning that it's approved for all risk patients, meaning that it's approved for all comers. So, now our job which we are having a very difficult time doing is to figure out which patient is more suitable for TAVR and which patients are suitable for surgical aortic valve replacement, because as you can sort of guess nobody wants open surgery, but we believe that there is a population that will benefit still from an open surgery. And you know, to identify that particular population is very difficult and very challenging.

Now, that brings me to one of my other questions though, and as we've seen a lot of these TAVR studies that we're seeing at AHA and being presented are based on procedures, let's say in a time span between like 2012 and 2015. or most of these studies, though, don't include data from the most recent years and as we know, TAVR has really become more streamlined and become a much more efficient procedure.

Do you think that we'll still continue to see improved outcomes like we've seen? Or what do you think the most recent data, when it becomes available will tell us about TAVR and who it's appropriate for?

Yeah, I mean, some of the most recent data are available with the recent trials. And obviously, the outcomes look much, much better. Number one, because you know, we're doing a better job, but also we're seeing much, much lower risk patients. So, we are going to get better outcomes with those patients in some of these trials compared to the outcomes that were reported in 2012 and 2015 during that time period, it's incomparable. I mean, the outcomes that we do for these low-risk patients, the stroke risk of 0.6%, operative mortality of 1%, less than 1% in 30 days, all these are just completely different from what we have seen in the past.

So, I think the TAVR procedure has become safer and better, safer and safer. And it's very easy to use as well for the procedure list and because it's so easy to use, and because it's so safe to use, I think the general consensus becomes, "oh, why don't we just do it on everybody?". And I think that's some of the things that that we sort of have to stop brakes on because most of the patients will definitely benefit from this minimally invasive procedure, but not everybody. I will have to emphasize that.

Right, thank you for that. And now, I want to also touch on a study that you took part in analyzing the utility of 30- versus 90-day outcomes as a performance metric for hospital rankings. And now I think one of the important questions that study raised is sort of where do we balance between the appropriate outcome measure for performance on TAVR versus the extra time and effort needed to evaluate over those long periods.

Yeah. So basically our study showed that that the 90 days correlates more than the 30 days outcome to the 1-year outcome. It sort of raised the question of the validity of getting all the follow-ups in 30 days, which is currently required by the TVT registry. So, the TVT registry collects all the data on patients who had transcatheter valve procedures, and they mandate follow-ups at 30 days and 1-year, but the follow-up rate at 1-year becomes substantially lower compared to 30 days. It also does put a lot of burden on the programs. You have to make sure that they follow up in one year and not all of them are reachable because some of them come from remote access and that really becomes a problem.

Our question really has become would 90 days be able to substitute you know, both 30 days and 1-year and minimize some of the burdens that there is for a routine follow up. I think this question is still wide open, because as you sort of mentioned prior this study uses the data from 2012 to 2015. So, these were mainly high-risk patients, and for low-risk patients, would this be true? We still don't know I think we have to find out with more recent data that comes out in the future.

Thank you for that. Now, one more thing I wanted to touch on in regard to sort of the new information about the nuances of TAVR or surgery, one that we had previously discussed, that came out of AHA was this analysis of the France-TAVI registry. Self-expanding valves were associated with increased risk.

Obviously, this wasn't a randomized controlled trial examining this was a sort of a retrospective look at it, but what did you take away from this study? And this is a bit of conjecture but is this something that you've seen in your experience doing TAVR for so many years?

You know, I think this is a very, very hard data to interpret because you know, they use administrative data from the French France registry and they retrospectively propensity-matched and tried to make it into an equal group and then compare the 2 which show the superiority in some of the outcomes of the balloon-expandable valve, but there are a lot of things that are hidden behind these statistics.

So, say, for instance, core valve, the balloon expanded self-expanding valve has some features that benefit certain anatomies. Say for instance, they can accommodate smaller vessels. So, if you have an iliac vessel that is not accommodating a balloon-expandable valve, a self-expanding valve may be feasible to do that.

Currently, we may be including more patients that has smaller iliac, which is not really captured by this administrative database. Moreover, if your institution is mainly doing balloon-expandable valves, the cases where you pick to do the self-expanding valves may be those that are extremely challenging that are not accommodating balloon-expandable valves. So, therefore, we may be including all these high-risk cases in there. And I just can't think of a way to completely exclude those biases and compare the 2 because this is not a randomized control study.

So, I think this is very provoking. The balloon-expandable valve may have lesser paravalvular leak and may have lesser mortality, but until we have a randomized control study, I don't think we can say that for sure. People are interested, but I don't think this was the format to completely answer that question. And this is just question provoking at this point,

Some more data that's come out very recently, I think it was published just earlier this week in NEJM relating to the timing of a SAVR procedure, and that how it impacts outcomes. It found that early surgery was associated with better outcomes than a conservative approach. Now, just from your experience, how does the timing of a TAVR or SAVR surgery related to the appearance of symptoms impact outcomes for aortic stenosis?

Just to clarify, Patrick, I think you're talking about the Korean study that looked at the surgical aortic valve replacement and am I quoting the right paper from New England Journal medicine?

So, that study particularly looked at early intervention become the for the patient becomes symptomatic, and had shown some benefit. The traditional teaching on aortic stenosis is that you wait until you're symptomatic because you sort of have to balance the risk and the benefit ratio, there's a benefit of doing an operation to prevent harm from the aortic stenosis. But you do risk your patients undergoing open-heart surgery.

So, you sort of had to scale that, that risk and the benefit ratio and come up with an equation and all the guidelines currently state that you operate when the patient is symptomatic, but this paper sort of challenge that dogma, saying that, maybe we should be doing the surgery earlier. And it sort of makes sense—you don't want your heart to be burnt out before you actually intervene on the valve.

There's actually an ongoing clinical trial sponsored by Edwards Lifesciences, called Early TAVR trial, which is randomizing patients who are asymptomatic into TAVR versus medical management. that outcome, I think, will be the most impactful one—understanding whether early Intervention really has a benefit or not. So, I think there is more increased interest in this subject, but I think we have to wait until this trial is completed for us to completely understand whether early intervention is truly useful, especially in the transcatheter realm.

I agree, I definitely think it's something to keep a close eye on as we go forward. And now just lastly, I wanted to touch a little bit on post-TAVR treatment, the GALILEO study and some other things that have come out look towards the impact of care following TAVR and how it impacts outcomes long term. Now, I just wanted similar to the very first question, what do you think has been the most impactful study or new data to come out regarding post TAVR care?

So, GALILEO definitely is one of the impactful ones because there has been a heightened interest regarding post-procedural valve thrombosis that was first reported by the Cedars-Sinai group when they were performing clinical trials for cortical valve. And there were concerns about these valvular thrombosis causing thromboembolic episodes or causing an early structural valve deterioration.

There was a presentation that was done at TCT looking at the PARTNERS 3 trial CT substudy analysis—this has not been published yet&mdash;but what they showed was that valve thrombosis that was seen or detected on the CAT scan at 30 days, some of them resolved without being on anticoagulation, which was thought to be one of the golden standard treatments because the original article stated that anticoagulation reverses those valves thrombosis.

In the most recent GALILEO trial, there's a CT substudy that actually showed that patients who are on NOACs have less chance of developing valve thrombosis. However, in the main trial, the GALILEO trial showed that being on NOACs actually has more harm than the benefit of the anticoagulation itself. They had a higher chance of mortality, and nobody can really beat that. So, routine use of anticoagulation after TAVR is basically axed because of this clinical trial.

I think we will have to learn a little more about the effect of valve thrombosis. I know that Medtronic will be presenting their low-risk trial data on valve thrombosis at this year's ACC. So, we're going to learn more about this but I think we're going to need more numbers and longer follow-ups to see the true effect of the valve thrombosis? Would it really be affecting the thromboembolic rates? Or in the long term, would it truly be affecting the structural valve deterioration?

I think those are the 2 questions that we don't know yet. And whether anticoagulation really is applicable for these patients. Despite the PARTNERS 3 CT substudy remains to be seen. I think a lot of the clinical practices still anti coagulate when we see these valve thrombosis post procedurally.

All right. Thank you for that insight. I totally agree. I definitely think it raises a lot of important questions. And just before we go, were there any other studies that you wanted to touch on that I might not have touched on during our conversation?

I think there's more and more data being published at this year's ACC. I sort of mentioned about the Medtronic sub-study for the valve thrombosis. There will also be data presented on the bicuspid aortic valve, which is another frontier that we truly do not understand at this point.

So, you know, in general, TAVR has established itself as a standard of care for aortic stenosis patients, but I think we're going to have to dig in deeply more and more to each subgroup to know the true nature or the true benefit of this. I think ACC is going to be a great start. We're going to see more and more in these subgroup studies that are truly important.

Yeah, I think it's just really incredible how quickly it's become standard of care and how much we still have to learn about it and how much it really seems like we have area for improvement, but I just want to thank you again for taking the time out of your busy schedule to speak with me today. And I hope to have you again on the DocTalk Podcast.

All right. Dr. Kaneko. Thank you again, and to our listeners. That's it for this episode. The DocTalk podcast. Thank you for listening.

The latest episode of the DocTalk Podcast features Tsuyoshi Kaneko, MD, of Brigham and Women's Hospital, discussing the most recent data and trends in transcatheter aortic valve replacement. 

DocTalk Podcast: TAVR Insights with Tsuyoshi Kaneko, MD

American Heart Association (AHA) 2019 Scientific Sessions

 meeting is behind us, it is safe to say it has been a big year in heart health.

From new guidelines to new therapies to new drug classes, every major conference has brought us new trials and information that will have tangible impact on real-world practice for years to come.

The end of 2019 also marks a bigger transition—one to a new decade. From the rapid onset of wearable technology to the expansion of SGLT2 inhibitors into the cardiovascular space, the world of cardiology has seen incredible advances from 2010 through 2019.

For more insight into how the biggest cardiology news in 2019 has shaped the ongoing landscape of the field, 

connected with Deepak Bhatt, MD, executive director of Interventional Cardiovascular Programs at Brigham and Women's Hospital and professor of medicine at Harvard Medical School, over the phone following AHA 2019.

That conversation is the subject of our latest edition of the DocTalk Podcast: A Year in Review: Cardiology in 2019 with Deepak Bhatt, MD, MPH.

Hello and welcome to this special AHA wrap-up edition of the DocTalk Podcast. On this special edition of the DocTalk podcast, you'll be listening to a phone conversation I had with Dr. Deepak Bhatt, as we discussed 2019 a year in review in cardiology.

I'm joined here today with Dr. Deepak Bhatt. Dr. Bhatt, if you wouldn't mind giving our listeners a brief background on who you are, then we can dive into our 2019 wrap-up discussion.

Sure, happy to be here. I'm Dr. Deepak Bhatt. I am the Executive Director of Interventional Cardiovascular Programs at Brigham and Women's Hospital and also a Professor of Medicine at Harvard Medical School.

All right, thank you for that. Now for our listeners. Dr. Bhatt and I had a brief conversation before this recording started and I decided to ask him about what I think are the three biggest takeaways from cardiology in 2019.

That would be the REDUCE-IT trial and icosapent ethyl, dapagliflozin and all the dapagliflozin trials, and last, but not least, rivaroxaban and the COMPASS trial. So Dr. Bhatt, if you could sort of take us through them and the impact they've had on the cardiology landscape in 2019.

Absolutely. Well, we will go with the order that you put them in. So I think, REDUCE-IT really is a landmark study that has opened up a whole new avenue towards cardiovascular prevention. The study, as you're aware, consisted of patients that were secondary prevention, but also high-risk primary prevention, meaning diabetes, and at least one additional cardiovascular risk factor, randomized to icosapent ethyl, a highly purified prescription form of EPA, or to a placebo. Finding a 25% relative risk reduction in major adverse cardiovascular events, including a significant 20% reduction in cardiovascular death.

So, those are the main findings and the results within the USA cohort—I'll add were particularly robust, including a significant 30% reduction in all-cause mortality. I just presented that recently at the American Heart Association. So, those are the reduce it results overall in the USA. And

I think in terms of implications to physicians, there are a lot of patients the data applied to because we did study abroad array of secondary prevention indications CAD, CBD, PAD, and the primary prevention cohort, specifically high risk diabetic primary prevention. That's a lot of patients within the growing number of people with diabetes. And the range of triglycerides we studied was actually including patients that are currently believed to have normal triglycerides—that is 10% of our population have triglycerides at baseline between 100 and 150. So, I think for a variety of reasons, the trial really will have a major impact on a large number of patients.

The second topic that you'd asked me to address was dapagliflozin and some data with respect to it. It was studied into the DECLARE trial where it was found to be useful in secondary and primary prevention patients extending the SGLT2 inhibitors story from higher-risk patients to lower risk primary prevention patients still finding benefit in endpoints such as heart failure hospitalizations, and renal endpoints. So, adding to the overall SGLT2 inhibitors story. DECLARE took us down to a lower risk diabetic patient, finding benefit in the primary prevention type diabetics.

So, a real contribution there from the DECLARE study, and then there was DAPA-Heart Failure a real breakthrough—I think. It examined dapagliflozin in patients with heart failure with reduced ejection fraction, but then also examined patients without diabetes with reduced ejection fraction&mdash;finding benefits in both with respect to death or hospitalization for heart failure and really similar degrees of benefit. So beyond just showing that dapagliflozin was useful in patients with diabetes, reduced ejection fraction which other SGLT2 inhibitor studies had essentially indicated but not in this prospective way, but still, the signals were all there.

That was confirmed, but then really extending our knowledge was the nondiabetic patients from DAPA-Heart Failure, who also benefited. So this really, I think, changes the way that we think about diabetes drugs and heart failure drugs and changes dapagliflozin for sure, and potentially depending on ongoing trials, other SGLT2 inhibitors from just being diabetes drugs to being heart failure drugs—even in those without diabetes. So, a major breakthrough.

Then the final trial you to ask me to discuss was the COMPASS trial—another trial that's really changed the way we think about cardiovascular risk reduction. A trial that showed the 2.5 milligrams twice a day of rivaroxaban. So a low dose&mdash;some people call it the Maschler dose of rivaroxaban&mdash;much lower than the atrial fibrillation dose, which somewhat normal renal function would be 20 milligrams a day, but to that 2.5 milligrams twice a day when added to low dose aspirin&mdash;81 milligrams a day&mdash;is superior to aspirin alone in a pretty broad population of patients with high-risk CAD or PAD.

Of course, these strategies of antithrombotic intensification are only applicable to patients at low bleeding risk, but in that patient who is at low bleeding risk, high ischemic risk due to stable CAD or as the European guidelines now call it chronic coronary syndrome and in those with PAD and especially in those with polyvascular disease that is a high atherosclerotic burden. Those sorts of patients benefit from rivaroxaban, including significant reductions in important endpoints, such as ischemic stroke, amputations, and acute limb ischemia, cardiovascular deaths with even lower all-cause mortality.

So, in the right patients at low bleeding risk, this can be a really useful addition. So 3 different trials or I guess you could say 4 because I threw in 2 for the dapagliflozin discussion that I believe have had a major impact, not just in terms of the drugs they studied, but more broadly, the implications. They have for the field of cardiovascular risk reduction.

I would totally agree. I think those 3 trials have really stolen away headlines or made headlines this year for very good reason. Now before I let you go, it's hard to believe it but 2019 is almost over and we're approaching 2020, which marks the start of a new decade. What do you think has been the biggest breakthrough or advancement in cardiology in this past decade from 2010 until 2019?

Well, you know, in fact, I think some of what we were discussing and some of what we haven't discussed would be the biggest breakthroughs of the decade and, obviously, I was involved with REDUCE-IT but I do honestly feel it's one of the major breakthroughs of the decade, not just in terms of the drug studied icosapent ethyl that surely looked quite good in the trial, but I do you think it'll lead to a whole new class of EPA or eicosapentaenoic acid-based therapeutics.

There is a lot of other research that's going on mechanistic research, imaging research with EPA. So I really do think we're at the dawn of a new era—and much like it felt when the first statins came out when the first large trials came out&mdash;like 4S, for example. I don't think people at the time fully appreciated what was going to be the case 10 years later with respect to statins, or 20 years later.

I think it will be the same thing with EPA were REDUCE-IT looks phenomenal as far as the results. But I think there's going to be all sorts of innovation in the space, other compounds down the road that will really help us understand how this EPA-mediated risk reduction is occurring and exploited even further. So, I think we're really at the beginning of an exciting new era of risk reduction that's based on EPA-related pathways.

The second thing I'll mention is related to what we discussed with respect to DECLARE and DAPA-Heart Failure, and dapagliflozin but now speaking more broadly about cardiodiabetology. The shift in thinking where diabetes drugs are no longer just confined to hemoglobin A1c reduction but rather where we started evaluating quite rigorously in the last decade the cardiovascular effects either bad or good of diabetes drugs.

I think that is an incredible shift in our thinking. Instead of just looking at biomarker reductions, hemoglobin A1c looking at heart events, things like myocardial infarction and stroke, and importantly, throwing heart failure into that mix—previously underappreciated, but now we realize that that's at least as frequent of complication in diabetes as myocardial infarction.

So, I think this focus on ischemic outcomes, heart failure outcomes, renal outcomes, how to improve them, and of course, also keep trying to improve microvascular complications is a real shift and it's in large part due to collaborations not just clinically but in research of cardiologists and endocrinologist and nephrologists and primary care and a variety of other groups. So, really an important shift in the way we are doing research in that area and also, I hope, in the way we practice with cardiologists becoming much more involved in the care of high-risk patients with diabetes, including their diabetes medicines.

The final thing that I'll mention is this incredible evolution in TAVR as a treatment for aortic stenosis, but also more broadly, structural heart disease moving away from open-heart surgery to minimally invasive techniques and by minimally invasive I mean truly minimally invasive catheter-based techniques, and for TAVR the data are looking spectacular across the risk spectrum.

Of course, we need longer-term data and in lower-risk patients before rolling out the procedure to young people or younger people, but still the data to date have been really amazing. And I think that there will be continued advances in mitral and tricuspid valve intervention and other aspects of structural heart intervention—interventions for heart failure, for example, I think we're right at the beginning of that. So, that's an area that I think we've seen a lot of great data, but there's much, much more that will come in the following decade.

Thank you for that. I totally agree as well. I think when we look back at 2019 in a few years, it wouldn't be a surprise if we see it as sort of a monumental shift and where we are going in terms of treating cardiovascular conditions. And now I just want to say thank you for joining us today. It's been a pleasure.

Yes, it was a pleasure speaking with you. Thank you.

 That's it for this edition of the DocTalk podcast. For the latest in AHA News and cardiology, be sure to head to MDmag.com. Thank you for listening.

A conversation with Deepak Bhatt, MD, MPH, discussing the most impactful advances in cardiology in 2019 and what he sees as the most important advances in the past decade as 2019 comes to a close. 

DocTalk Podcast: 2019 in Review with Deepak Bhatt, MD, MPH

Hello everyone, and welcome to the DocTalk podcast. I’m Kevin Kunzmann, managing editor of 

, and I’ll be your host for this special edition of DocTalk.

Normally, our show features a one-on-one conversation with a clinical expert. Each episode is typically 10-20 minutes, and focuses on one topic of healthcare at a time. But this week’s episode is going to be a little bit different.

About a month ago, I was asked to moderate a panel discussion on 

 stigma with a team of public healthcare policy and advocacy experts. The panel was part of the 2

 Annual Advancing Mental Health Policy: BetterTogether Forum, from Otsuka Americal Pharmacuetical, hosted in Washington, DC.

Today’s episode is actually the live-recorded audio of that 45-minute discussion, featuring the excellent insights of our panel:

Tammy Boyd, Chief Policy Officer of Black Women’s Health Imperative

John Snook, Executive Director of the Treatment Advocacy Center

Jeff Valliere, Director of Communications at FasterCures

Listen in to the audio transcript of a policy- and public health-based discussion on mental health stigma from a panel of experts.

DocTalk Podcast: Mental Health Stigma Panel

 for the treatment of diabetic kidney disease, the treatment became the first in nearly 2 decades to receive approval for that specific condition.

Approval of canagliflozin is based on the results of the phase 3 CREDENCE trial. Trial results demonstrated the oral therapy was associated with a 30% reduction in risk to progression of end-stage kidney disease, doubling of serum creatinine, and renal or cardiovascular death among patients with CKD and type 2 diabetes, compared to placebo.

The double-blind study, which included 4401 patients, showed the drug—along with standard care&mdash;was associated with a 32% reduction in end-stage kidney disease alone (HR, 0.68; (95% CI, 0.54 — 0.86; 

 = .0015). Canagliflozin also reduced risk of cardiovascular death and hospitalization for heart failure by 31% (HR, 0.69; 95% CI, 0.57 — 0.83; 

= .0001) and major cardiovascular events (MACE) by 20% (HR, 0.80; 95% CI, 0.67 — 0.95; 

Additionally, there were fewer reported adverse events and serious adverse events among the treatment arm, with no statistically significant difference in incidence of amputations or adjudicated fractures.

With studies like CREDENCE and DAPA-HF, which showed the potential for dapagliflozin for the treatment of heart failure, continuing the showcase the versatility of SGLT2 inhibitors, they also leave many with questions about the potential mechanisms behind these treatments. As more and more data supporting their use for conditions, the questions and curiosity surrounding SGLT2 inhibitors also continues to grow.

For a better look at the recent approval of canagliflozin, the mechanism behind it, and where clinicians could expect canagliflozin to fit into their treatment regimens, 

sat down with George Bakris, MD, professor of medicine and director of the American Heart Association Hypertension Center at the University of Chicago Medicine, for the latest episode of the DocTalk Podcast.

Hello, and welcome to the DocTalk Podcast. I'm Patrick Campbell, Associate Editor with MD Magazine. I'll be your host for this edition of the DocTalk Podcast as we discuss the recent approval of canagliflozin with Dr. George Bakris.

Dr. Bakris, welcome to the DocTalk Podcast. If you could just give our listeners a little bit of background on who you are and your involvement with canagliflozin—then, we can dive into our discussion.

I'm Dr. George Bakris, I'm a professor of medicine and director of the American Heart Association Hypertension Center at the University of Chicago Medicine. I was involved in the CREDENCE trial in terms of development of the protocol and I was on the steering committee of the study and actually was a recruitment site.

Now, I guess we can just dive into the question. So, I think the first thing is: what does this approval mean from a physician-centered standpoint?

Well, I think it actually makes life easier if the physicians are willing to accept this. It basically is one drug that will control sugar, it's one drug that will preserve kidney function, it's one drug that will actually aid in blood pressure management, and it's not associated with some of the effects of some of the other drugs that would be prescribed in this setting, including hyperkalemia and acute kidney injury.

So, it's really kind of a multipurpose compound that has multiple mechanisms, many of which are still being explored. I think for the practicing physician, it gives them license to prescribe this drug even more than metformin because with metformin you have to adjust dose when the GFR falls to below 45. Here, there's no dosage adjustment needed and you can prescribe it above a GFR 30 and you can keep using it below 30. So it's really kind of a no brainer, to be honest with you.

From a patient centered standpoint, what does this mean? Is this sort of a cure all for them or is this more of an add-on therapy?

So, this is not a cure all by any means, but it is an adjunct of medicine to already what is considered standard of care. What I mean by that is, if you add this medicine—if you add the SGLT2  canagliflozin&mdash; to the armamentarium of what the patient should already be on, including ACEs or ARBs, and other glucose lowering medications, lipid-lowering medications, you're going to further delay decline in kidney function by 58%, you're going to reduce the risk of heart failure substantially, and, fundamentally, you're going to improve glycemic control, especially in people with estimated GFRs above 45. The beauty of this label is you can certainly use this drug, even in people below a GFR of 45.

You should not think of this as a glucose-lowering medication. In fact, you should think about this as a cardio-renal risk reducing agent that happens to have glucose-lowering as a side effect. That's actually, the way this drug works. It's really got anti-inflammatory properties—we really don't know the full mechanism of how this drug is working.

So, it's very important to understand, from a patient standpoint, they're getting additional benefit that they may not realize on multiple fronts, including blood pressure, including glucose for many, and even some uric acid lowering, etc. None of this specific stuff is in the label for those specific risk factors, however, that benefit is there. So, I think the patients should view it as kind of a multipurpose pill that is helping longevity and, primarily, reducing morbidity. There's no greater morbidity then going on to dialysis and there's no greater morbidity and being put in the hospital for heart failure. And clearly, the canagliflozin clearly prevented the death or reduced the risk.

Okay, now, I'm glad you touched a bit on the mechanism for canagliflozin in that last answer. What does it say about canagliflozin and sort of the versatility or the robustness of it, that it became the first drug approved to treat diabetic kidney disease in two decades?

Well, the truth is, it's the first drug that was actually studied in people with intense kidney disease. There are now two other studies following, but the results of those won't be available for at least a year, if not longer. So, that's part of it, but I think when we sat down to actually start talking about this, and I'm talking about in 2012. We speculated that mechanistically this drug could have benefits on the kidney because it would have hemodynamic effects. We had no idea about what has recently been found with this class of drugs and it turns out, it's an explosion of activity.

Many people think this drug is a mild diuretic, and it causes glycemic loss. Well, that's true when you're GFR is 75 to 80. But when your GFR a fire is 30, that is not true. You're not losing glucose in the urine, you're not getting a reduction in GFR, you're not getting the hemodynamic effects that were described, when it's higher up. So, then, how can it possibly work? and actually help predict the kidney? Well, it turns out that there's recent studies and I when I say recently, I mean, these are just published literally within the last year to year-and-a-half and there's a panoply of them.

One is that they block the kidneys ability to generate angiotensinogen, which is the precursor to the renin-angiotensin system. Now, some people have interpreted that as this is like an ACE for an arm that couldn't be farther from the truth. This works at a cellular level, to blocking angiotensinogen production, independent of ACEs and ARBs, and that's only seen in diabetes.

So, is that an explanation? Well, we just had data to suggest that in non-diabetics from the DAPA-heart failure study, that may not be a mechanism because you're getting a benefit in non-diabetic patients as well. Now that's one.

There's another mechanism really relating to the NLRP3, and RP3 inflammasome. The inflammasome is something that's in cells, it's kind of a shark within the cell. It cleans up a lot of inflammatory things and the SGLT2s actually potentiate this is actually speculated to be one of the potential mechanisms, along with facilitating ketone use in the heart for reducing heart failure risk. There's actually data suggesting the adipose site, which in obese individuals with diabetes, is a very inflammatory organ, and the SGLT2 actually quells some of the inflammatory cytokines that come out of that. There's more, I mean, we could spend the whole time talking about that.

This is just the beginning of understanding what these drugs can do. The other thing is people think SGLT2 s are only in the kidney and they're nowhere else. Well, it turns out, much to the chagrin of many, that cells have the ability to actually synthesize the transporter. It's been found in cancer cells. It's been found in glioblastoma, pancreatic cancer, lung cancer, prostate cancer. So, clearly, if the cell needs it. It's there. People say there's no SGLT2s in the heart. Well, in the normal heart, that's true. But is anyone looked at a failing heart? No. So, we don't know if it's there.

We really are just scratching the surface mechanistically and just assume these drugs are just dumping glucose in the urine and we're done. That turns out to be a very naive interpretation of what these drugs can do.

That really leads well into my last question for you, as you touched on canagliflozin and SGLT2 inhibitors have a ton of uses and we're finding more and more about them—it seems like&mdash;with each and every study. What do you think is next or could we see any potential other indications coming down the road?

Well, I don't see it being developed as an antihypertensive that actually was proposed years ago, and nobody went there. I don't see it being proposed as a drug to aid in prevention of gout. And so, what else can you do? I think, really, if I had to say something, I think you have enough now, to make it standard of care. I'm not at liberty to discuss with you the upcoming 2020 ADA guidelines, but I can tell you, they're going to be a little different than what you currently have.

I think within the next year to year and a half, this class of drugs is going to be mandated like the ACEs and the ARBs to be standard of care in people with diabetes and have high risk for cardiovascular and kidney disease because of the overwhelming benefits. We're going to have the DAPA-CKD trial coming out the end of next year. I can't imagine that's not going to be positive.

So, the data is literally just going to be piling up. It'll just be overwhelming. If you're not using these agents, it's going to be troubling. In fact, I can tell you, there's a couple of trials coming out next year. One is the FIDELIO trial, which is in kidney disease, but looking at a nonsteroidal mineralocorticoid receptor antagonist and that's 5300 patients and of those 5300 patients, about 8% are on SGLT2s. We've already planned—because I'm the principal investigator. We've already planned and analysis of that subgroup to see if there's additive benefit, with a mineralocorticoid on top of the SGLT2. So, we're kind of treating it as if it makes standard of care.

So, I don't think there's any question that there's not going be anything new necessarily—We've got heart failure now, we've got kidney disease, and prevention of dialysis. We've got reduction of cardiovascular risk. How much more do you want? I mean, that's the pretty much the Full Monty, as far as I'm concerned.

Okay, that was about it on my questions. Was there anything else you wanted to add that we might not have touched on?

George Bakris, MD, professor of medicine at University of Chicago Medicine and member of CREDENCE steering committee, discusses the recent approval of canagliflozin and what it means for diabetic patients and their physicians. 