New Heart Failure Guidelines

TRC Editor, Dr. Lori Dickerson, PharmD, FCCP talks with two distinguished experts about new heart failure guidelines. 

• Carolyn Lam, MBBS, PhD, FRCP, Professor at Duke-NUS Medical School and a Senior Consultant at the National Heart Centre Singapore
• Steven E. Nissen, MD, MACC, the Chief Academic Officer at the Heart and Vascular Institute and the Lewis and Patricia Dickey Chair in Cardiovascular Medicine Professor of Medicine at the Cleveland Clinic Lerner School of Medicine at Case Western Reserve University

Listen in as they discuss new guidelines for managing heart failure with reduced ejection fraction (HFrEF)...and put this new guidance in perspective.

You’ll also hear practical advice from panelists on TRC’s Editorial Advisory Board:

• Andrea Darby Stewart, MD, Associate Director, Family Medicine Residency at Honor Health
• Anthony A. Donato, Jr., MD, MHPE, Associate Program Director, Internal Medicine from the Reading Health System, and Professor of Medicine at the Sidney Kimmel Medical College at Thomas Jefferson University
• Craig D. Williams, PharmD, FNLA, BCPS, Clinical Professor, Department of Pharmacy Practice at the Oregon Health and Science University

For the purposes of disclosure, Dr. Carolyn Lam reports relevant financial relationships with Bayer, Roche Diagnostics (grants/research support); Abbott, Actelion, Alleviant Medical, Allysta Pharmaceuticals, Amgen, AnaCardio AB, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Cytokinetics, Darma Inc., EchoNous Inc, Impulse Dynamics, Ionis Pharmaceuticals, Janssen, Merck, Novartis, Novo Nordisk, Roche Diagnostics, Sanofi, Siemens Healthcare Diagnostics, Us2.ai (advisory board/steering committee/executive committee); Us2.ai (stock shareholder); Us2.ai (non-executive director).

Dr. Steven Nissen reports a relevant financial relationship with AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Esperion, Medtronic, Novartis, Pfizer, Silence Therapeutics (grants/research support).

The other speakers have nothing to disclose. All relevant financial relationships have been mitigated.

Pharmacist’s Letter offers CE credit for this podcast. Log in to your Pharmacist’s Letter account and look for the title of this podcast in the list of available CE courses.

Email us: ContactUs@trchealthcare.com.

The content of this podcast is not intended to be a substitute for professional medical advice, diagnosis, or treatment.

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Transcript

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Narrator 0:05

Welcome to Medication Talk, the official podcast of TRC Healthcare, Homopharmacist Letter, Prescribers Letter, RX Advanced, and the Most Trusted Clinical Resources. On today's episode, we'll be listening in as our expert panel discusses new guidelines for managing heart failure with reduced ejection fraction, HEFREF, and puts this new guidance in perspective. Our guests today are Dr. Carolyn Lamb from the National Heart Center Singapore and Dr. Stephen Nissen from the Cleveland Clinic. You'll also hear practical advice from panelists on TRC's Editorial Advisory Board, Dr. Andrea Darby Stewart from Honor Health, Dr. Anthony Donato from Reading Health System, and Dr. Craig Williams from the Oregon Health and Science University. This podcast is an extract from TRC's Emerging Recommendations Panel webinar. Each month, experts and frontline providers discuss current medication therapy topics and practical recommendations to include in TRC's letter articles. The full webinar originally aired on April 20, 2022.

CE Narrator 1:11

And now, the CE information.

Narrator 1:15

Pharmacist Letter offers CE credit for this podcast. Please log into your Pharmacist Letter account and look for the title of this podcast in the list of available CE courses. For the purposes of disclosure, Dr. Carolyn Lamb reports relevant financial relationships by receiving grants, research support, being a stock shareholder or a member of an advisory board, steering, or executive committee with Abbott, Actilion, Alleviant Medical, a list of pharmaceuticals, Amgen, Anacardio AB, Applied Therapeutics, AstraZeneca, Bayer, Bohringer Ingelheim, Boston Scientific, Cytokinetics, Dharma, Econos, Impulse Dynamics, Ayonis Pharmaceuticals, Janssen, Merck, Novartis, Nova Nordisk, Roche Diagnostics, Sonofi, Siemens Healthcare Diagnostics, US2.ai. Dr. Stephen Nissen reports a relevant financial relationship by receiving grants or research support from AB, Amgen, AstraZeneca, Bristol Meyer Squibb, Eli Lilly, Esperion, Medtronic, Novartis, Pfizer, and Silence Therapeutics. The other speakers you hear have nothing to disclose. All relevant financial relationships have been mitigated. Now let's join TRC editor, Dr. Lori Dickerson, and start our discussion.

Lori Dickerson 2:28

We're talking about this now because big changes in guidelines will lead to debate about managing heart failure with reduced ejection fraction or hefref. So, Steve, to get us started, how has the treatment of hefref historically evolved to the standard triple therapy to reduce morbidity and mortality?

Steven E. Nissen 2:47

So it's extraordinary. I mean, during my career, uh, we've gone from really having diuretics for heart failure, first evidence around ACE inhibitors, and then evidence has then been added for additional classes of agents. And along came beta blockers, and they had an extraordinary effect on both morbidity and mortality. Uh and mineralocorticoid receptor antagonists became very popular. And then along comes secure balsartin. And you know, all bets are off because uh in a head-head trial, accualsartin vested uh the results from an ACE inhibitor or an ARB. And so we now have a multitude of therapies, and as you point out in this article, we've got to figure out what do we deploy and in whom and in what order.

Lori Dickerson 3:42

That's a great overview. Thanks so much, Steve. And so we are used to this triple therapy for Hefref, and now we're going to be thinking about quad therapy and what should be in that quad therapy. So let's dig into what's new and first focusing on changing guidelines versus sort of the application in practice. So we're going to think about the guidelines changing first and talk a little bit about that, and then we'll talk about sort of how to handle that in practice. So, Carolyn, can you briefly explain why the US and European guidelines have changed to suggest entresto as a preferred agent instead of an ace or an AR when possible?

Carolyn Lam 4:19

Well, Dr. Nissan already alluded to it. It was the literally paradigm shifting results of the paradigm trial. Now, remember, this was a huge global trial where the new drug, psychopature balsartan, at that time, was compared to the established therapy in allopril. So this is not a drug place depot trial. It was against active treatment with inalopril. And here psychopature valsartin had just possibly demonstrated benefits compared to inalopril with a 20% reduction in cardiovascular death and heart failure hospitalization. So I think it's mainly because of this landmark trial as well as subsequent trials like the pioneer trial showing that it was just as an efficacy in new onset heart failure and started in patients hospitalized with heart failure and uh subsequently uh the proof heart failure study showing that there was cardiac reverse remodeling with acrobatics are to it's increasing data that this is really, really uh the uh preferred choice. And so I think the 2022 American guidelines has really made it very clear that it is ARNI first. And if you uh don't tolerate um an ACE or inhibitor, or if you don't tolerate an ARNI, actually, you couldn't consider an ACE or ARB. And in fact, they strongly now even say if you're on an ACE and ARB, consider switching to psychopaths article. The ESC guidelines were a little bit more conservative in saying that if you have on an ACE and if you continue to have symptoms, then continue switching.

Lori Dickerson 6:12

Gotcha. Okay, great overview to get us started there. And so now let's talk about this quad therapy or the four-legged stool from the three-legged stool. We've written about the three-legged stool before, and now we're writing about a four-legged stool or quad therapy. And Carolyn, can you again briefly comment on why uh the SGLT2 inhibitors are now added as the fourth leg or the part of quad therapy to standard hef ref therapy?

Carolyn Lam 6:40

Well, that was because of another two blockbuster heart failure trials. And I still remember being in the room when the DAPA-HF trial, which was the phase three trial of DAPA glyphosate, the SGLT2 inhibitor against placebo in patients with heart failure with reduced ejection fraction, uh, really read out strongly positive and pleasant on top of that triple therapy that we're used to ends the fourth leg. Um and that was very, very rapidly followed by the Emperor reduced study also showing in totality that the addition of SGLT2 inhibitors saves lives, keeps patients out of hospital, makes patients feel better, and all in a very convenient once-a-day single dose, so no uptitration involved, and you know, very well tolerated too in general.

Lori Dickerson 7:38

Great overview again, Carolyn. Thank you for sort of setting that stage. And um now I want to talk a little bit about what folks are seeing um on in the community practices and in other hospital systems in terms of uptake of these. So, you know, Andy, uh, we are seeing some comments come in about you know the practicality of these new guidelines. Um, and I'm wondering, are you seeing more use of entrusto and SGLT2 inhibitors for HEFREF in your hospitalized patients yet in your sitting?

Anthony A. Donato 8:06

Uh a lot more entrusto, uh not nearly as much of the SGL2 and two inhibitors. I I actually looked this up today for you. Um, we were about 5% of our systolic heart failure um uh six months ago or up to about 15%, but uh the cost continues to be a very big issue and getting them approved.

Lori Dickerson 8:25

Got well, we're definitely going to address those things. Yes, Steve, go ahead, jump in.

Steven E. Nissen 8:28

I want just to jump in and say that uh there's sort of a disconnect here. And the disconnect is that most heart failure now is not being managed by experts, not by the Carolyn lambs of the world, but by, you know, often, you know, uh general practitioners, family practitioners. And the the uptake of these therapies has been slower, even triple therapies. And so if you look carefully, the patients that get admitted to our hospital are often not on optimal therapy. And so we really have an issue with we're we're now adding a fourth component, but we haven't really uniformly gotten people to even give the three components. And um, you know, the the three components, if you just take ACE or ARB uh plus, you know, a mineral corticoid receptor antagonist and a beta blocker, those are pretty inexpensive and they're not being used. So we can't we can't say this is all due to pharmacy benefit managers. We got an awful lot of people that are not on the therapies they should be on, even when those therapies don't cost anything.

Lori Dickerson 9:37

Great segue there, Steve. And you see on the screen now in our next uh paragraph in our article says but less than 1% of patients with hefref are on triple therapy at target doses, plus adherence in clinical trials is much higher than in real-world patients. So, Andrea, I'd like to hear from you, you know, about the routine challenges that you're facing in your primary care family practice, managing these folks and getting them to target doses and managing triple therapy, let alone before we get to quad therapy.

Andrea Darby Stewart 10:08

Yeah, absolutely. No, I you know, one of the things that I've always appreciated about this group is the discussions that we've had about collaboration between primary care physicians and our uh cardiology colleagues in this area. Um, and so uh when I'm able to have good communication with the patient's cardiologist and we're taking patients back and forth, and I'm able to maximize their medications and um get agreement with the patients as well that I am equally capable of increasing their medication doses and will communicate with their cardiologist, it works really well. Um, I think the bigger challenge is that we're just having people take a lot of medications, and we know med adherence is um really a challenge, and you know, adding a fourth medication, um let alone the cost of that medication, has really been a challenge with in the context of my patients. And um what I'm seeing in our hospital is that many times patients um who come in with a new exacerbation are switched to entresto or um or they're started on entresto with their initial um heart failure diagnosis. And we've had several who have left not filled their prescriptions because they couldn't afford them, and then come back again fairly rapidly with um escalation of their disease process. So it's been an ongoing conversation with my cardiology colleagues that just because the medication is a great medicine doesn't mean that people are going to be able to willing to pay for it and able to take it as directed.

Lori Dickerson 11:37

You know, Andrea, to add to that, you know, I think we've written also uh in this piece and discussed about, you know, most people with heart failure have many other comorbidities. It doesn't just come alone, right? You've they've got diabetes and other things, and and so it's not just really these four meds or five with maybe a diuretic, it's a lot of other things that are coming along with it, um, which makes it a difficult balancing act. Um Steve, I just wondered if you have anything to come back from that and any any comments, I guess, in terms of that collaboration and how how folks can work on working together.

Steven E. Nissen 12:14

Well, that collaboration, I mean you put it very well, Andrea. You know, we we have to work together. And, you know, there are not enough cardiologists on the planet to take care of every heart failure patient. We have to rely upon a collaboration with primary care physicians. Um I would feel a whole lot better about these this situation if we could just get most people on good triple therapy. And then for those people that are not doing well on triple therapy or who can afford, you know, the the extra costs, have a discussion with the patient. Um, you know, kind of a mutual, you know, joint decision making, you know, do we want to add additional therapies? What is the pill burden like? All these points are very well taken. I find it disconcerting that so few patients are on even good triple therapy. And, you know, I don't know how we fix that problem.

Carolyn Lam 13:16

Could I add a global perspective uh to what Steve just shared? So, Steve, I just couldn't agree more with you. And, you know, just to let you know, the issue is of course not just the United States. We just published um a paper of report to heart failure, which is this large global registry of hospitalized heart failure. And on average, this is not even talking about being at target doses. This is just being on the three baseline medications, and only the three, not the four, was only present in slightly more than a third of patients at discharge. Can you imagine that? So we're not even looking at being on high doses less than um, you know, a quarter of the patients who should be on these three medications are not throughout the world. And the people who are least likely to get them are women, those who don't have insurance and those who don't have follow-up. And so we've shown that, and and it really builds to the fact that this collaboration and partnership between being in the hospital and then transitioning of the care uh to primary practice and so on is just so, so important. And in fact, the guidelines um uh do emphasize that that the transition is so important, having follow-up is so important.

Lori Dickerson 14:48

Go ahead, Craig.

Craig Williams 14:50

Oh, I think someone else chimed me in. But uh I I will I'll just add I think it was Annie, but these comments are all spot on, and it's uh we literally were working on a new diuretic guidance for our inpatient staff and got an exact conversation these exact conversations three months ago. And you get a little bias on the inpatient side because you kind of see patients who are failing for a number of reasons when they're hospitalized, but uh yeah, that not a week goes by that I don't have to wear both the kind of patient-centered care advocate hat and the outcomes-based kind of pharmacologist clinician hat on this topic, and it seems like it used to be for hypertension, and then diabetes became the kind of polypharmacy problem, and now it's exactly heart failure. So it's a wonderful problem to be in, um, but but it is a problem. These are all great comments that we're not gonna be able to solve and come with a paragraph that fixes it tonight. It's just for everyone to be aware of what's in the guideline and do our best to apply it to all the patients we're seeing every day in our practice.

Steven E. Nissen 15:43

There is one thing we've been able to do that seems to have made a difference. And we now have a discharge process with a discharge checklist, and we involve pharmacists in meeting with the patients and counseling them, finding out about their capability of you know, paying for their medicines. So it's a multidisciplinary collaboration that's helped us whittle away a little bit this problem.

Anthony A. Donato 16:09

Lori, this is Andy. Um two things I think are important here. One, uh, it's really hard to push these doses right at time of discharge. A lot of times because they have some renal insufficiency, they are a little hypotensive. The studies I've seen that have worked very well have used some of our nurse practitioner colleagues that see them every two to four weeks, and they have a strategy of dial up meds each time, make sure they're not in a little bit of failure. Uh, but that is basically resource intensive. Uh, the other thing I'll say too is that I see a lot of clinical inertia. Somebody tries one time to move an ace, they see the creatinine bump or the little bit of low blood pressure, and no one ever tries again. Because these patients they will equilibrate, and you can push drugs, you just have to give it multiple chances, and I see people kind of give up quickly.

Lori Dickerson 16:55

These are great points, Andy and everybody. I really appreciate this discussion because you know, we could focus our whole article on on this issue, and you know, we do say um in uh the next paragraphs consider whether this new guidance is practical for your patient and continue to focus on optimizing traditional triple therapy first. It can cost under $30 per month. And so I think we've all gotten this point. Um, and uh I just also wanted to make um the comment that our you know community pharmacy colleagues out there too can help uh push adherents and and help partner with patients who are maybe not understanding why they're on multiple medications and can can also be in addition to the pharmacists in the health system who might be helping with that, this could also be carried out to our community pharmacy colleagues as well. So great great points here. And um, you know, Craig, one more thing that we discussed in the pre when we were preparing this article was about adherence in clinical trials versus adherence in real-world patients. And I think you had some comments here about you know, these are great numbers needed to treat that we have with SGLT2s and in tresto, and um, that they are obviously um very low numbers and represent an important therapeutic initiative, but how might that be different with you know standard adherence versus clinical trial adherence, Craig?

Craig Williams 18:24

Yeah, no, and it's uh you know it's every patient is their N of one study. So as I spend more time on the inpatient side than the outpatient side, I mean as I said, we're we're seeing patients who are kind of failing things. And in our discussion now on our diuretic adherence uh protocol here, there's a comment on exactly co-therapy and think about these other agents before they go home. But the understandable pushback from internal medicine was if patients are here because they're failing to take two or three medicines properly, we you know, we don't want a protocol telling us to add three or four more medicines. So to Andy's point, the inpatient side is often not the place to get this done. But to Steve's point, it's an opportunity to do some real education and to dig into things. And yeah, you know, I as a pharmacist working on the hospital side, oftentimes we're peeling away some medicines when we realize patients can't handle the burden. And rather than letting the patient go home with 15 things and choose what they're gonna take and not take, you know, we're trying to make those choices for them. So sometimes pharmacists are helping peel away and not adding on therapies. But yeah, every patient is unique. And and I appreciate these guidelines, they're very evidence-based. We're you know, we're decade into guidelines being evidence-based and based on trials, and they're telling us what we need to know. It's just now we're we're butting up against a real world application of that. But but yeah, the real world is different than studies, which is always a point, I think, well taken between academics and and all of our colleagues in the real world.

Lori Dickerson 19:44

So that being said, um, I think uh we we know where we've been, and now let's talk about where we're going here in terms of applying these new guidelines. And you know, we state that if if patients still have heart failure symptoms, uh consider switching from an ACER ARB to entresto. And so, Carolyn, I guess that's my first question to you. Do you agree with this statement of reserving entrusto for folks who still have heart failure symptoms on a maximally uh you know titrated Acer ARB or tolerated Acer ARB?

Carolyn Lam 20:16

Yeah, thanks, Laurie. That's a good question. And it's not a question that can only be answered based on the science, and I think that is the main thing. We have to consider the patient as a whole, and of course, cost and all these other considerations come into play. If we just look at the science, obviously the answer I think would be yes, because clearly um uh uh interestal robustly meet inalbral uh the the usual ace. Um and this would be if I had part of it with reduced ejection fraction, for example, if any of us had and knew that there was a better alternative, I think we would all realize that that would be sort of a choice we would want to make. But then the other considerations come into play. And here um I'd like to maybe share that that uh we've we've uh think about sometimes a heart leader spending function, if I may. And and that is uh we see a patient come in and they have uh reserve banks of different things, of blood pressure, of potassium, of creatinin, um, of literally money in the pocket, and so on. And I think sometimes it's our role as doctors to help them optimize the spending of from these various reserve banks to really get the best return of investment in terms of survival and feeling better and improve quality of life. And so this would definitely be something uh that Steve has already alluded to a conversation uh with a patient. Um it's very difficult to have a patient who's got no symptoms and feeling very well uh uh to consider going on a very expensive med and change. Things and potentially having side effects.

Lori Dickerson 22:03

You know, Steve, I wonder we're getting a few questions coming in about uh the idea with this NNT being so low, uh, you know, should people who are doing well on an ACE or an ARB, you know, should you consider proactively switching to entrusto uh or only really in folks who have persistent symptoms? And I'm wondering how you handle that.

Steven E. Nissen 22:27

Yeah, I do. I am proactive. I mean, look, when you have these kinds of benefits, you know, morbidity mortality benefits that are that robust, the goal should be to get as many people as we can on circuital valsartin rather than an ace or an art. Now, there may be other considerations that make that less practical, such as costs, such as coverage and other things. We have found that we can fight through the coverage battles now with circuital valsartin much more successfully than we could when the drugs drug was launched. And so we're getting more and more people on them. But I have to tell patients, I must tell patients, we must all tell patients that these are drugs that can reduce your risk of morbidity and mortality. Now there may be considerations for why you may not be able to take the medicines, but we have to tell people that there is a benefit.

Craig Williams 23:30

I do think entresto is a one to really kind of push for here. And when you look at the data, as as Kaylin and Steve are saying, you know, it's entresto is about as better than an ACERB as ACE ARB was compared to placebo. When you look at the outcomes data, and I think when you kind of put it that way, the clinicians, a lot of them really they buy into that one. So and it's kind of replacing a therapy patient on as opposed to adding a new therapy. So I think we're seeing much better uptake with that than SGL2s, like Andy had shared. And but I agree that that's the one to kind of push for now and make sure people understand that data for that really is quite robust.

Carolyn Lam 24:01

Carol. That's a great point about that bill burden uh that the um ARNI doesn't add to that. But I was going to point out that the new American guidelines have value statements, which I think are it's it's a very useful thing, and it's new for the guidelines. And um in these, ARNI replacing ARNI, uh replacing the AIDS with an ARNI, or starting an ARNI instead of an ACE, um, have been shown to have high economic value. So that's that's very encouraging.

Lori Dickerson 24:30

And it is certainly when we're looking at a population and it um becomes you know difficult, I think, you know, in a busy primary care practice. And I bet that's kind of what's uh you know going through your mind, Andrea, and thinking about these, and we haven't even talked about the SGLT2s yet. Uh but I'm curious about your thoughts, Andrea, um about switching proactively versus thinking about doing that just in folks who are having persistent issues.

Andrea Darby Stewart 24:57

You know, I think that the the balance of the individual versus the population is an important one that we all need to consider as physicians in this country, considering our dysfunctional medical system. Um, for my patients who have economic means and we have a shared decision-making discussion, and um even if they're doing well, I can let them know that uh switching to an RNE may be in their best interest. And for them as an individual, I'm hopeful that that will be the case, that there are the one in the 21 that um, or I'm sorry, the the one in I can't remember what the number needed to treat was, but that we can prevent 21.

Lori Dickerson 25:31

Yeah, that's right, you're right. Yep. Yeah, yeah.

Andrea Darby Stewart 25:33

Um that we can prevent um uh an exacerbation with. Um, but for many of my patients, um this really will just continue to be an economic burden that they're not willing to um to choose. And so I think the balance is in the discussion. And you know, my area of expertise is providing um that shared decision making and trying to balance all organ systems in the patient along with their financial and social viability.

Lori Dickerson 26:01

And looking at this, of course, numbering to harm that we have here noted too, causing low blood pressure at about one in 21 patients, too. Um, so looking at those pros and cons, Andrea, of course, are part of that shared decision making. And you know, I want to actually just uh have this very similar discussion, Carolyn, um, about the SGLT2s and adding that fourth leg of the stool or that quad therapy. Um, and so I'm curious are your of your thoughts about doing this proactively versus sort of reserving SGLT2s for patients who have uh persistent symptoms on triple therapy, which might include intrusto.

Carolyn Lam 26:38

Right. So I think many of the considerations that we've talked about apply here too, but there is this extra thing with the SGLT2 inhibitors. Remember, it started off as a treatment for diabetes. And so both the American and European guidelines are consistent in saying that it's a class one recommendation that if a patient with heart failure has diabetes, we should consider using the SGLT2 inhibitor for the reason of the diabetes, and that makes a lot of sense because it will also help the heart failure. So we're we're maybe talking about in patients who don't have another indication, perhaps, like they don't have diabetes and they have heart failure and they seem to be um doing well on on triple therapy. Well, I have to admit that um in my current practice, I reach for the SGLT2 inhibitor very, very often. And it's because in terms of pill burden, it's a single dose. In terms of needing up titration, you don't. In terms of the tolerability, um, yes, one of the commonest things we've seen is genital urinary infections, but there is plenty that the patient can do to actually uh prevent uh these infections, you know, uh genital hygiene and so on. So um I do think that it is uh amazing in the scientific evidence of the benefit that we get, um, not just in survival, but also making patients feel better in terms of quality of life.

Steven E. Nissen 28:18

There is one more factor that I uh want to always think about, and that is the renal protective effect of the SGLP2 inhibitors. It's sort of amazing that you got one class of drugs that treats diabetes, treats heart failure, and it slows the decline in renal function. And uh, you know, you don't get very many therapies that can do all three of those things simultaneously.

Carolyn Lam 28:42

Yeah, great point, Steve. It builds to what Andrea was saying earlier about you know keeping all the organ systems in mind. You're you're absolutely right.

Lori Dickerson 28:51

And go ahead.

Anthony A. Donato 28:52

This is Andy. Just one one point that's probably very obvious to everybody, but uh uh for patients, a re-hospitalization generally, they're not on the hook for the drugs they are. So the economic decisions, yes, as a system as a whole, we should put everyone on them. But for the patients that have to make these choices, this is often not eating or not buying a gift for their grandkids. So I think we have to keep that in mind.

Narrator 29:14

We hope you enjoyed and gained practical insights from listening into this discussion. Now that you've listened, you can receive CE credit from Pharmacist Letter. Just log into your Pharmacist Letter account and look for the title of this podcast in the list of available CE courses. If you're not yet a Pharmacist Letter subscriber, find out more about our product offerings at trchealthcare.com. Be sure to follow or subscribe, rate, and review this show in your favorite podcast app. It helps spread the word about our show and is a great way for you to let us know how we're doing. You can also reach out to provide feedback or make suggestions by emailing us at contact us at trchealthcare dot com. Thanks for listening to the Medication Talk Podcast.