All right, good evening, everyone. I am happy to open up our spotlight session on modern lipid management, the updated medicine cabinet. My name is Dr. Martha Gowady. I'm the president-elect of the American Society for Preventive Cardiology, and I have the honor of chairing this session tonight. And I share the stage with three of my colleagues, Dr. Christy Ballantyne, who's a professor of medicine, professor of genetics, and the section chief of cardiology at the University of Pittsburgh. I also have Dr. Salim Virani, a professor at Baylor College of Medicine, and Dr. Carol Watson, the co-director of the UCLA program in preventive cardiology from UCLA Medical School. I also would like to introduce our fellow in training, Dr. Anam Saeed, who is with us and will be our clinical facilitator, basically keeping all the attendings in line. But she will also be taking your questions in this program. We'd like to thank Amgen and Novartis for their grants to support this event. And just so everyone knows, you will get a link in your email to get your CME, MOC, or CME credits. So just look for that after this session ends. This is probably the most important slide. We'd like you to play with us, play along with us, if you don't mind. And using the ACC22 app on your mobile device, maybe many of you already have it downloaded. It's what's been guiding you to the different programs. And if you're like me, it's been helping me find the map to each of the rooms. But in this, you select the session that you're in right now. It is a listed session. And then in there, you'll select the audience response icon. And then you'll respond to our different polls that we're going to present to you. And additionally, there's a place that you can write in questions. So as we're talking, we're not going to have questions till the end, but we will have a lot of time for questions. So please enter those questions in, and we will get back to them. So again, I'll just hope everyone knows how to find this audience response. And if you have any trouble, just raise your hand, and some of our team out there will come and help you with this. Okay. I think people know this. Masks are required except here on stage when we're farther apart from each other and except when you're actively eating and drinking. So here's our first polling question, because we actually do have this being broadcast live to people that aren't able to be here. So we just want to know, how many of you are participating in this session, either A, in person, or B, virtually? It's like Jeopardy. You get a little bit of music. And I did not choose this music. They say I can't hasten it past 60 seconds. It has to be 60 seconds. So... We will find out how many people are watching this at home. It's pretty late in many different All right. So the majority of people are here. So thank you for coming. And for those of you at home, we hope that you also have a good interactive experience with us. All right. So we're going to go through a few questions at the beginning just to see what your knowledge base is. We won't give you the right answer just yet. But just a few questions, six questions, I think, if I remember correctly. So the first question is, which of the following is not a predisposing factor associated with statin-associated muscle symptoms, or also known as SAMs? A, older age. B, male sex. C, Asian ethnicity. D, alcohol use. And E, rheumatologic diseases. Please go ahead and tell us what you think. I probably shouldn't have moved that fast. I apologize. But hopefully you can see it on the app. 60 seconds is a really long time. So Martha, I'm glad you didn't pick this music. I did not pick this music. Next year we're going to put in a request list. All right. Here we have the response. You can see 42% say male sex. Second highest response was Asian ethnicity. We'll get to that. All right. So question two, which one of the following favors a clinical diagnosis of SAMs? A, symmetric, proximal, large muscle pain or weakness worsened by exercise. B, symptoms beginning two to four weeks after statin initiation. C, resolution of symptoms within two weeks after discontinuing statin medication. D, symptoms returning within two weeks after reintroducing statin therapy. E, symptoms occurring with two or more statins, at least one of which is prescribed at the lowest dosage. Or F, all of the above. Uh-oh. It says connection disorder. Here we go. All right. Most of the responses are in. So here most people think all of the above. All right. Question three. Clinical trials of proprotein or let's just call it PCSK9 inhibitors have demonstrated which one of the following results? PCSK9 inhibitors provide similar LDL lowering as statins and therefore similar clinical benefits for primary prevention. B, PCSK9 inhibitors are less effective in patients at higher risk. C, the clinical benefit of PCSK9 inhibitor therapy on ASCVD events is related to an individual's absolute risk and amount of LDL reduction. Or D, PCSK9 inhibitors reduce ASCVD events, but overall benefit is limited by adverse events. Okay. All right. Let's see. The commonest answer, 90%, say C. All right. Question four. The mechanism of action for inclisirin includes degradation of which one of the following regarding PCSK9? So A, PCSK9 protein, B, PCSK9 mRNA, C, PCSK9 gene, or D, PCSK9 receptor? Okay. Let's see everybody's response. So most people chose PCSK9 mRNA. And then question five is effective and durable LDL reduction is seen with 300 milligrams of subcutaneous dosing of inclisirin every, so the dosing question, A, 30 days, B, 60 days, C, 90 days, and D, 180 days. Choose what you think it should be. Okay. All right. All right. Most of you picked 180 days. Next most common answer is 30 days. Let's go to the last question. The last question is, bempidoic acid, 180 milligrams by mouth once daily has been added to a patient's lipid lowering regime, which includes atorvastatin, 80 milligrams once daily, and azetamide, 10 milligrams once daily. Which one of the following tests may be reasonable to monitor at follow up? A, creatinine kinase, B, high sensitivity CRP, C, uric acid, or D, hepatic transaminase levels. All right. All right. And most people chose D, hepatic transaminase levels. So now through our talks, we will try to answer all these questions for you. And I'm just going to tell you our program because this is a pretty rapid review on our lipid lowering management in this modern era. I'm going to start by talking about optimizing statins. Dr. Ballantyne will continue the conversation with non-statin therapy. Dr. Watson will speak about inglycerin. And Dr. Varani will talk about bempidoic acid. So we're going to do quite a quick through affair of lowering LDL. And then we'll definitely, like I said, leave time to ask questions. So again, please enter your questions if there's things that you want as we're going forward. So I'll start by talking about optimizing statins. And I don't have any disclosures. But I think it's always good to reflect on history. And, you know, we've had more than a quarter century of LDL lowering. And many of you have probably seen this slide by Dr. Sabantine who gave me permission to use it. But we, you know, we first knew that high LDL was bad. And then we found that, you know, even when it was average, it wasn't that good. And lower was always better. And then we learned that. We learned initially from statins. Then from ezetimide, we learned even lower LDL is better. And then from PCSK9 inhibitors, we've even learned that even lower than that is better. But for statins, you know, we have the most randomized control trials of any, really probably any part of medicine. You can see here for primary prevention shown in the red line, secondary prevention shown in the blue line, all the different trials that we've had related to statin therapy. And I think that that just tells you, you know, we've had evidence. And getting the LDL down has been a target of our treatment and has ultimately entered our guidelines. And you can see that within our guidelines, you know, whether we're talking people with clinical atherosclerotic cardiovascular disease, that statins are the mainstay of our treatment. Of course, other parts of other medications can be used. But for all of it, we are recommending statin therapy because we have the most evidence. And then for primary prevention as well, once we've identified people at risk, we, again, statin therapy is part of the guidelines. It's the first part of our guidelines that we start with. All the other medications are second. So, of course, I think most people in this audience, we all use statin therapy. We know statin therapy well. But you would be surprised at how much statins still are underutilized. So a medication that we've known so well and still underused. Now, the benefit of LDL lowering therapy, of course, initially you get some benefit. And you see it by lowering the LDL. Really, the benefit comes even greater over time. So the longer somebody is on statin therapy, the greater reduction in cardiovascular events. The problem really has come that, you know, despite good guidelines, and people would argue that the guidelines that preceded the 2018 guidelines, there was a lot of controversy. Some societies didn't agree with what the American College of Cardiology and the American Heart Association said. And they were reconsidered about in 2018. Well, this Gould study looked at this. They looked at, you know, what happened then to prescription patterns across the United States. And you can see shown here, really, statin therapy, you know, really didn't change in terms of its use. The idea of using high-intensity statin therapy didn't really change. Use of azetamide slightly went up from about 13% prior to the guidelines to 16%. And PCSK9 inhibitors just went up just slightly from 2.9% to 4.6%. So we really haven't, despite having good guidelines, we haven't really incorporated them more so into our practice. The Gould registry also showed that only 17% of patients with atherosclerotic cardiovascular disease received intensive lipid-lowering therapy. And two-thirds within this registry remained with LDLs above 70 milligrams per deciliter. So these are people with atherosclerotic cardiovascular disease that we should be achieving at least under 70. So in terms of statin adherence, long-term statin adherence in all-cause mortality, there's an inverse association. And this is just one study by Dr. Rodriguez that has shown that, what the comparison group was the people that adhered to their medications and took it more than 90% of the time. They compared it to the other three groups that they stratified as 70% to 89%, 50% to 69%, or less than 50%. And you can see here that all-cause mortality, if you were less likely to adhere to statin therapy, that you had worse outcomes. Now there's a lot of reasons why patients don't adhere to statin therapy, the biggest one being due to statin-related side effects. So when we look at our placebo-controlled trials, they don't show an excess withdrawal when they're in the statin arm compared to the placebo arm. But what we do know is that statin compliance does change over time. And there's many different factors that play into why patients are not able to continue statin therapy. Things that happen in the prescriber office. So in our office, if the patients don't have a good understanding of the benefits of therapy, they're less likely to take the medications. If their medications are denied after giving them a prescription, of course they're less likely to take them. Financial difficulties in getting a medication, or the polypharmacy just having yet another medication in their pile, that may be the medication that they sacrifice, even when it's generic. And health literacy, of course, can affect whether, you know, if you hand a patient a piece of paper describing things about statin therapy, and if they don't have good health literacy, and you don't take the time to make sure they understand what's on that, they may not take their medications. Then there's other barriers in terms of the pharmacy. So when they go to the pharmacy to pick up their medications, of course there's the idea of perceived side effects. Especially for statins, you can go... Our patients, we all know, Google statins, and they can see lots of reasons not to take statin therapy. Again, from when they're filling it in, they may not understand what the pharmacist is saying in terms of the benefit or risk. Whether that even conversation happens there might be questionable. Polypharmacy is a big issue, and when a pharmacist advises them that another medication might interact with it, then you're going to also see patients be less likely to take it. And again, denial is less likely for a patient, obviously, to get the medication. For the patient themselves, you know, the reasons that they're less likely to take it, that includes forgetfulness, side effects, of course financial limitations in polypharmacy, and of course ongoing reinforcement. If they look at their cholesterol levels and their LDL improves, a lot of patients think that that's it, I don't need to take it anymore. So that ongoing reinforcement about why we're giving this medication needs to be a constant part of their clinic visits. We know that sometimes when we think about statins, we worry, you know, patients are always worried about statin-related side effects. And I love the SAMHSA trial. Very nice trial where the patient was their own control. They were assigned to four months of statin therapy, four months of placebo therapy, and four months where they knew they were getting nothing. So they were very well aware because it was an empty bottle four months. And what they found is that when they were on no treatment, they didn't really have statin-related side effects. With placebo, they did, though, have lots of statin-related side effects that they reported. And when they had statin therapy, they also had side effects. But 90% of them had side effects on placebo. And they understood when they were on nothing, when they didn't take any medication, that those symptoms went away. So the proportion, the nacebo proportion, was about 90%. And at six months, almost 50% of these people went back to clinically taking statin therapy because they understood when the results were described to them, they understood that even when they were taking nothing, like, you know, the placebo, that they reported the same effects. So they understood that they were maybe perceiving these side effects. So we can't underestimate even the nacebo effect, but we need to be able to address it with our patients. Patients really do get side effects from statin tablets, but 90% of their side effect burden can be elicited by placebo tablets as well. And being an N-of-1 trial, as in the SAMHSA study, where they had a period with no tablet, this really revealed to the patients clearly that for 50% of them to restart their statin therapy. And we know that for many patients, we can't get them to restart any statin after they report a side effect. So I think that the side effect is often from just taking the drug, not from what's in them. I'm not trying to minimize what the patient's reporting, but sharing this information can really help us manage our patients. So from the clinical experience versus randomized controlled trial, you know, the elephant in the room is always related to statin-associated side effects. Those statin-associated side effects include muscle symptoms, worsening glucose tolerance, CNS side effects, and elevated transaminases. And the diagnosis of SAMHSA is favored if they have a symmetric, proximal, large muscle pain or weakness that's worse with exercise. It's also favored if their symptoms begin within two to four weeks after statin initiation, and if there's resolution of symptoms within two weeks of discontinuing, and that their symptoms return within two weeks of reintroduction. Symptoms also occur if they occur with two or more statins, and at least one of those statins being at the lowest dosage. So there's a nice allogarithm that you can use to manage and work up your patients. If they don't have a CK elevation, give them a two to four weeks washout of a statin, then re-challenge them with a different statin, maybe at the usual or the starting dose. See, if they're symptom-free, you can obviously work to achieve their LDL at the level that you want to get them at. If their symptoms recur, then you might use a different statin. We rarely have patients who have rhabdo or CK elevations four times the upper normal limits, but at that point, you need to wait for at least six weeks for washout of statin before even introducing a second but low-dose statin therapy. We need to not forget, though, that patients are on other drugs, many of them that might not be cardiac drugs. To remember them from medical school, I always remember this rag camps. I don't know if that helps anybody, but that's the way I was taught to think of these other drugs that could be interfering and causing statin-associated problems. I also would remind you that the American College of Cardiology has a statin intolerance tool that you can download or use in your clinical setting. I find it nice to work with the patient and fill in this intolerance tool, use this intolerance tool with them because it helps them see why I'm asking them certain questions. It can help us work together as a shared decision-making tool. The question in here is, should my patient be on a statin? Well, there's an app for that, and we have the ACC ASCVD Plus app that I hope many of you use that helps us identify the patients that need to be on a statin. I'm going to pass it over to my colleague now, to Dr. Ballantyne, and we'll talk about non-statin therapy.

lipid management

statin therapy

adherence

side effects

SAMSON study

non-statin therapies