Terrific talks by everyone and we're gonna start taking the questions and Adam I don't know if you want to come up here and join us as well but we've got some good questions that we'll start right now. Did you want to do the cases first? Yeah I'll ask a couple and we're gonna do a couple cases as well so let me just ask a few questions here that came up. A question for anyone who wants to answer is should coenzyme q10 be given with statins and if so what dose? Do any of you use coenzyme q10? I sometimes do use coq10 you know you talked about nocebo so my thought ends up is that those are really hard to give a nocebo or a placebo but I can give coq10 for someone who complains of statin I said this may help or it may not help so for some people it does help is that a placebo effect? It might be because the trials are not very definitive on this so therefore an actual dosing is not set but and there's some expense but I have had patients who say that they feel better as long as they'll take their statin that's what my goal is there so the individual trials were all very small and none of them individually showed benefit but in a recent meta-analysis they did show a slight benefit and there was no harm so it's a feel-better drug not a live longer drug so I tell patients you get to decide what to do with it. And mechanistically I mean coenzyme q10 levels of the blood do go down because it's in the same pathway but where do we need coenzyme q10 in the muscle but it's the respiratory chain. It's transported in lipoprotein. Exactly. So if you lower LDL it's gonna go down but in the muscle where you really need coenzyme q10 for in the respiratory chain if the levels don't go down so I think as long as there's no harm if a patient is going to be able to tolerate their statin therapy which has a lot of benefits perhaps okay. Great and one more question I'll ask you is actually I'll direct this to Carol what is the volume of the injection for in glycerin and then also does anyone know the expense? I do know the expense the company is decided to price it equivalent to what PCSK9 inhibitors would be for a year. So remember PCSK9 inhibitors you're taking every two weeks or four weeks that cost that that would be for the year they've priced the twice yearly in glycerin injection the exact same price. The volume I I come up whoever asked that question I'll get it for you I know I have it but I can't come up with the answer. No we didn't do any of the trials that the other thing comes up is the the methods of doing this is it's a build basically you can either get it you do it in your office or you can send them to an injection center or an infusion center to get get the injections with it. It's done a little bit differently in terms of building by is one of the approaches towards this with it but it's what it's very well tolerated. All right Dr. Saeed thank you good evening everyone. All right I'll start with the first case for it's an audio response option and we'll go through the case and you can answer and we'll get the panel to discuss further. So case number one is a 62 year old black woman with a history of coronary artery disease she had an end STEMI about six months ago with a PCI to her circumflex hypertension and dyslipidemia who presented for a follow-up visit. Since her last visit she has improved her lifestyle, is adherent to a heart healthy diet, exercise approximately 60 minutes per week and consumes 12 to 14 glass of wine per week. She does not report any limiting symptoms. Dr. Saeed, we don't see it on this on the screen see if you. Sorry. We see it here but we don't see it on the screen. Did you click on your presentation? Yeah there you go. All right we're back on. Anyhow 62 year old black woman coming with a history of coronary artery disease, hypertension, hyperlipidemia. Since her last visit she has improved her lifestyle, is adherent to a heart healthy diet, exercise 60 minutes per week and consumes 12 to 14 glasses of wine per week. She does not report any limiting symptoms with her exercise. She has lost approximately five pounds in the past six months. She was prescribed Resuvastatin 40 milligrams after her PCI about six months ago and has been taking it regularly. Prior to this she was statin naive. Recently she stopped a zetamibe due to abdominal cramps. Her current medications are aspirin, Resuvastatin 40 and Carvidolol 6.25 milligrams. And her physical exam, she has a BMI of 27.6 percent. Her vitals appear to be stable, otherwise she has a normal and unremarkable physical exam. She's worried about her health saying that the heart attack was an eye-opener for her and she wants to discuss a residual risk of cardiovascular disease events and how to lower this risk further. She says, Doc, I prefer no medications at all unless completely inevitable to reduce my risk without them. You see her current labs and this is what they look like. Total cholesterol is 220 milligrams per deciliter. Her HDL cholesterol is 53. Her LDL cholesterol is 116 milligrams per deciliter. Triglycerides 198 and her TSH was 1.68 and her hemoglobin A1C is 5.8 percent. What is the best step forward in managing Mrs. Smith's ASCVD risk? And I will start the timer with this. All right, we should have this percentage up here, but it's interesting. I would, since we don't have what the audience really answered, we didn't get the polls, but I'd like to ask the panel about what they would do with this lady. I think one thing I was interested in was, I would definitely be interested in knowing what was her LDL cholesterol level before her event, because on treatment, it's 117. Either she is not adherent, which is not uncommon, and a patient saying, I'm taking the medication, is perhaps not reliable, so if you have a pharmacy refill data, one should make sure that the patient is actually taking the medication. What was her baseline LDL cholesterol? Is she one of those non-responders to LDL cholesterol? Because with Resorastand 40, you should probably be close to 50%. Of course, not everybody responds the same way. And if there is any resistance to statins, this may be one of those patients where you may want to check for Lp little a as well. And so those were the three things I could think of that are clinically important, in my mind, to be checking before we move on to the next therapy, which is appropriate. But right now, we just need that LDL down, so I want to get it down. Yes, I would agree with the answer here about adding a PCSK9, because it's 116 LDL. Her non-HDL was almost 170, so she's really quite elevated in terms of Apo, B-casein, and lipoproteins. And she needs to, this issue of convincing her that this is her best chance to avoid having another event. So I think she may need, this is where the discussion you mentioned, you know, you, Mark, you were talking about this, it's a joint decision, because if she's not taking her medicine, she won't get any benefits. So there may be a discussion, persuasion, and then some concerns. And one of the things that we found helpful is to show them, this is a pin, at least for the, if it's a monoclonal, it's a pretty easy, it's very easy to do with it. And we frequently give the injection in the office. And then if someone was going to be using in clostridine, you give that in the office also frequently. So it gets them through that first, you know, a little bit of a, I don't want to take an injection. And most people, once they do it, I would have been very pleasantly surprised how well it is tolerated. By the way, the in clostridine injection volume is 1.5 milliliters, but the PCSK9 injection volume is one. So it's not that much more. Yeah. The other thing would be, in this particular patient, just because of how she is, what concerns she is, you know, mentioning to us, it would be extremely important when you get that first repeat LDL cholesterol, that you actually show her the results. This is the kind of patient where you're going to show that this is what the therapy is doing. Should always be done, but I think it's even more important in this patient. Yeah, and one of the things that comes up is, you don't need to wait long periods of time to check LDL. I mean, you're going to find out very rapidly. So someone could get, you know, we did frequent after the third injection, just before the third injection, if it's a model home, that's six weeks. But it's the same thing if you're adding a ZMI. If you're increasing statin dose, you get all of your impact between four to six weeks. So sooner is better than later to persuade somebody that it's worth it. One of the few things that has shown improved adherence is actually someone seeing the results of the lab tests and seeing for this stuff. If you don't get follow-up labs, you're going to have a reduction in adherence. You get 80% of the statin reduction in two weeks. Yeah. I think also for these patients who, like this woman who doesn't want to take medication, sometimes, you know, you'd be, if you didn't give a PCSK9 inhibitor, just as an assumption, oh, well, they won't take an injection. Actually, an injection sometimes is the one thing they will take. So just, again, don't make assumptions that patients won't take things. I think we have a question. Yes, so with either a ZMI or a benpedoic acid, the reduction you're going to expect is going to be far from the 70 milligram per deciliter goal that you're having in mind. So wouldn't it be better to just go straight to the PCSK9 inhibitor? That's what everyone said. Yeah, the option really, the answer is D here. She's too far away from it, yeah. Yeah, and just to remind you, she stopped taking a ZMI because she was having some abdominal cramps. Right. I'll move on to case number two here. That is a 46-year-old white hypertensive woman seen in the preventive cardiology clinic for the first time seeking consultation for hyperlipidemia management. Her most recent lipid profile shows an elevated LDL cholesterol of 198 milligrams per deciliter. Approximately four years ago, she was started on simvastatin but had to stop taking the medication because of adverse side effects manifesting as myalgias. She does not recall the doses or the frequency she was started on. Her myalgias, she says, promptly resolved after stopping the medication. She's active and enjoys exercising on her Peloton bike four times a week and takes over the counter supplements. Her past medical is hypertension, GERD, iron deficiency, anemia. Her OB histories, she is preeclamptic which progressed to eclampsia. She delivered twins at 32 weeks and a family history significant for father at MI age 46 years and had a history of high cholesterol as well. Her twin sister has an elevated cholesterol diagnosed early in her 30s. She's an ex-smoker, does not use any other drugs, social alcohol use. Her physical exam has a BMI of 25 kilograms per meter square. Blood pressure is normal, heart rate's 72 and she has trisubstantin symptoms present on her physical exam. And these are her labs where she has a total cholesterol of 282, triglycerides 188, her HDL cholesterol of 46 and LDL cholesterol of 198 milligrams per deciliter. Her HSCRP, which is high-sensitive CRP, is normal. Her TSH and her LFTs are normal and there's no protein urea and vitamin D levels are normal. You do check a lipoprotein A, it's 191 nanomoles. The question is, what is the next best step in lowering this patient's atherosclerotic cardiovascular disease risk, event risk? Oh. All right, hopefully we'll get the knife, there we go. All right, panelists, Dr. Gulati, Dr. Watson. I think that's a reasonable first step. I mean, there might be some other things I would have done with this patient given some of her risk enhancers. I probably, to help decide just how low I need to go with the LDL, I probably would have got a coronary artery calcium. Despite the fact that she's a young woman, the history of preeclampsia, we know have an increased risk of coronary artery calcium prematurely. That might help us know where we want to get with the LDL. But that aside, I think for someone who's been on simvastatin, had side effects, I don't like that drug anyway. So I would try another statin, and natorvastatin is fine to try as well, and see if she tolerates it. Sometimes in exercisers and in women, it can be that they will have muscle-related side effects to statins, but it's worth trying before you go to the other medical therapy. I would try to get her on some dose of some statin. I don't know if she'll make natorvastatin 20 or 40. I want to get her on something. She may end up on 5, but then I know I'll need to add something like a PCSK9 inhibitor as well. Yeah, so she, I mean, by the family history and the finding on physical exam, she has familial apocryphalemia. She has FH. Yeah. She has FH. That's important. She's got FH. Her dad was young when he had his event, and then she smoked with it, and had LPA. So I'm very worried about her risk, and we'd like to see her well under 100 ideally. Well under 70. Yeah. So I think, you know, she's somebody, you've got to get her, I agree with you, get her on a statin, whatever she'll tolerate it. She's willing to take, but she's going to need something in addition to that. The only thing I would add is that, as Dr. Ballantyne mentioned, this is probably a real FH. This is not one of those LDLs above 190, which is most of the patients who don't have any of the four well-defined mutations. With her family history, tendons and thoma, and such premature family history, she may have real FH. Now, if you have access to genetic testing, that might help as well. It may just give you the duration that she's had such high LDL cholesterol levels that may make you worry more, although we have enough here, I believe. And then making sure that her kids are tested, and other siblings, I think she has one twin sister who was tested, but others may not. It was high. It was high. She was diagnosed with high cholesterol in her 30s or something, right? So just making sure everybody in the first-degree relatives, including her kids, are tested I think would be extremely important as well, since it's autosomal dominant, if she has real FH. So you're using the lipoprotein A as one of your arguments that PCSK9 will have an inhibitor, will have benefit, but that's not an approved indication at this point, is it? I didn't use it as an argument for about lowering LPA. I'm using it as an argument for her risk status. It is an approved issue that we treat FH with PCSK9 inhibitors. And so if someone is higher risk, just like Martha was saying, a calcium score, I don't think that the PCSK9 inhibitor will lower the calcium score, but it will lower her risk for events. Now, it turns out in the trial data, people with high LPAs had the higher event rates and they had greater benefit, and some of that by statistical methodologies, at least in the odyssey outcome they felt was related to the LPA reduction, but that's really not the issue. The issue is it's a risk marker for her. I understand, but LPA still could be a target for her, and I'm also concerned with the diagnosis of familial hypercholesterolemia, that the statin, like you said, is clearly going to be insufficient. And are you just going through your paces by starting her on a statin drug, or why wouldn't you go straight to the PCSK9 inhibitor? Go ahead. I would do both, because all of the PCSK9 studies are indicated on max-tolerated statin. That's the FDA indication. And is there any role for that other drug, pelicarcin, for LPA treatment? It's too late to go, she wouldn't have qualified for Horizon Outcomes, and you know, it's only available if you're in a trial. Yeah, it's experimental still, and I completely agree with you. We just have no data yet that lowering LpA will confer benefit. We're hopeful, but we don't have data yet. I understand. You are hopeful, and I'm hopeful too, but I... Okay, well, the study's fully enrolled, so we'll find out in a few years. And SafeHeart is the study in FH patients where LpA, as Dr. Ballantyne was mentioning, actually provided further risk stratification. So if you have those double hits, I mean, you're at higher risk. It just makes sense. Yeah. Like you said, this lady's dad had a heart attack at 42, and if you did a pedigree, you might find that a second cousin and an uncle had those young deaths too. So you really need to make a quick difference on this lady. Absolutely. Thank you for that. We do agree. So the rationale for this is, you know, clearly this is a patient with familial hypercholesterolemia requiring more reduction in her LDL cholesterol. So we would re-challenge her with a reduced and alternative agent of a statin therapy here, and clearly she will likely eventually need something more aggressive, like a PCSK9 inhibitor. So the same patient, she has started on atorvastatin 20 milligrams daily, and she has recurrence in her severe myalgias. A CPK level is obtained and is normal. She's re-challenged with lower dose and lesser frequency of atorvastatin, however, has recurrent symptoms. She finally tolerates rezuvastatin 5 milligrams three times a week, and this is her follow-up blood work after four months, where her LDL cholesterol is 140 milligrams per deciliter. Her coronary artery calcium score was done, and it was 71, which is at the 99th percentile for her gender, her sex and age. What is the next step in lipid-lowering therapy escalation here? Sorry, due to some technical errors, we will not be receiving the final answer or what the audience thinks, but we do have our panelists here, luckily, and I think we sort of went through this, but. Yeah. Yeah. Okay, yeah, we can do that. Who wants to go with A, start bile acid resonance in addition to rosuvastatin? Great. B, stop rosuvastatin, start on pitivastatin. C, ezetimibe 10 milligrams. Some hands, a few hands, okay. We'll give it 10% of the room. D, start PCSK9 inhibitor therapy. All right. Maybe 50% of the room. And start in glycerin E. All right, another 10, 12%. Okay. I will direct to Dr. Ballantyne. Well, I would talk to the patient and say we need to do something extra here. We have two options. We can use either a PCSK9 monoclonal antibody. There is a newer therapy that's approved in glycerin. You'd have a dose, then three months, then every six months with it for that. But then you can, people will ask you what's the evidence in this and that. So, but, you know, I think you want to, there's an informed discussion here, but clearly the first three are not going to do it. I mean, we need to get her LDL down a lot lower with it. She needs to go down. And, you know, you need another 50% or more reduction in this patient. Yeah, she's at 140 milligrams per deciliter. Dr. Varani, would you do something else? What would you? No, but I would not throw out Ezetimibe totally, though. I would utilize it. Actually, guideline directed answer may be Ezetimibe here. But what I would say is I would talk to her. I mean, you know, you'll get 18, 20% LDL cholesterol reduction. 18, 20% of 140 is not trivial. So that could be part of the discussion as well. But I think we have a lot of ground to cover. And this is the one where you may not get an answer from a guideline. This is where a clinical judgment has to be used based on what we are seeing, that this is one of those patients where there's a bloody in terms of primary versus secondary prevention kind of thing, right? Very high calcium score for age, risk factors, family history. So you could do multiple things here. One of the challenges in real life clinical practice for us country cardiologists out there in the sticks is that the companies sometimes require maximum tolerated statin, maximum tolerated acetamide, and still the copayment for these patients is three, $400 a month. And these blue collar folks just can't afford it. It's insane. So one of the key things is you have to have this note written that says, patient has heterozygous familial epichlostrolemia. That has to be in there. Then it has to say on maximally tolerated statin, the LDL cholesterol is 140. Therefore, it requires additional treatment with it. So then that'll get it approved. You may have to send it twice, because they like to reject it, even if all the data is there. And then they'll depend. Then the next thing, unfortunately, is which the insurance company approves it, but they frequently change the drug that gets approved, preferred drug every six months, just to create more work for us with it. So it may have been Alirocumab, and it goes to Evolocumab, or it goes back and forth with it. I've found that copays have gone down. So it's a lot better now than it was when it started, for the most part. But you're still, they like to reject it. But if you write the note and have all those words in there, maximally tolerated statin has to be in there. And it doesn't, if they require acetamide, acetamide, she's still gonna be over 100. But despite all that. He's more optimistic than I am. You can write all those things, and they can still reject, or still give you a copay that's way intolerable. And I agree that they. We've had about 98% we get through. So we almost never have one that doesn't. So I don't care, let's say maybe, it also, it's part of the country, though. So it may be tougher in LA. I know there were some states where they were rejecting people right and left. Yeah, but I do think you will, some people will get the call that, did you try acetamide? And then the problem is, is the acetamide may not lower the LDL enough. So we end up spending so much money, and ultimately the patient might end up on three drugs rather than two as a result. But I agree, some people will get that call that they won't be approved. But they approve it. Despite all that, they approve it. But the copay, the patients, the part they have to pay, 300, 400 a month, and a lot of people can't afford it. So this is a call for pharmaceuticals to reduce the price. I read the Wall Street Journal. I know what they make. Well, yeah. 100%. The price of the drug is 500 a month. The price of either of these drugs, it's actually a little less than that right now. It's under 6,000. So if they're only paying, if they're paying 300 a month, they're basically, they get the drug for that. I mean, because they get a discounted thing, so they're not covering anything. This is an issue with the insurance company basically being completely unfair, which happens not infrequently. Many of the drugs you pay for, your copay when you're getting a generic drug costs more than the generic drug costs, for example, CVS or something. Go ahead. My question is, just tagging along with that other, the previous question. One of the things, I was very optimistic about the Inclisirin because number one, my understanding was that it costs more to manufacture drugs based on monoclonal antibodies than it does to manufacture drugs based on MRA technology. Correct me if I'm wrong, but that's what I understood. Second thing is that I thought with the administration of the drug of basically twice a year as opposed to twice a month, it seemed like to me the cost should be less. So I don't quite understand how you can justify or the company can justify charging the same amount of money based on those two factors. I wish I could get in that pharmaceutical company head. I relayed your concerns today to someone, but they were explaining it's a lot more complicated. Unfortunately, we do have a very complex system with PBMs in between, and what they've set up is their argument is that if someone has Medicare and supplemental and it's given in the office, there's no co-pay, which sounds great. It's just that then you have to buy the drug and administer it. So it's kind of beyond our conversations right here. We don't, this is not medical knowledge. This is like- I wish we could control this. But it is, stay tuned. We'll see what happens on this. And hopefully, I know it's improved for the PCSK9s. It's much better than it used to be, but I will say that I've never seen therapies that are so effective and so safe with so little utilization. So it's really, for our patients, it's just, I think we need to get this work down because we're missing out on something that's really helping our patients. One of the quick- Something we were so excited about, and then when it came, we were unable to use in so many patients that needed it. Yeah, but I would not give up. I found that it's getting better if you're persevering, and then you can get the therapy to the patients. One quick follow-up question. If you have the choice between one of the monoclonal antibody PCSK9 inhibitors and the Inclisirin, why would you ever use one of the monoclonal antibodies? Wouldn't it much be easier to just use Inclisirin and be done with it? We're waiting on outcome studies. Thank you. With respect to statin intolerance, I agree so much with partnering with the patient and making sure they understand, but again, I have to say that in practical day-to-day management, I cannot have a parent-child relationship with patients. I simply don't have the energy and time to follow up and repeatedly try these drugs unless I have the assistance of a pharmacy clinic, perhaps, but some patients, like with the vaccine, have made up their minds on these issues, and so if docs are going to be rated on their percentage of compliant patients, so often comes up so much noncompliance, and then you talk about insurers paying for drugs that patients just don't take, then there is some stuff being thrown away, but the talk that I heard, I felt that there was still a bias to treating the patient as a child and the doctor as the adult who has the responsibility. I think the patient shares tremendous amounts of responsibility in whether they're going to partner in their own disease. For sure. No, I agree. I mean, it's a partnership, right, and so from a patient's point of view, we've gotta work with the patient in front of us, but it's hard, because there's so, first of all, there's so much out there, and everybody Googles all their medications, and they get convinced. They forget that they had muscle aches before they even came in and saw you, but once you give the medication, that's a problem, and then additionally, for those of us who are cardiologists, another person may have already started the drug and not talked about what their baseline was beforehand, and so it is a struggle, and I think we can do the best we can do, but I think that some of those tools, if you're able to use them with your patients, I find them effective, but I agree that sometimes our time is limited, and we can't have those involved discussions, and it's futile, and you sometimes know that the patient in front of you, that we're not gonna win this fight, either. Thank you. Dr. Mali, question. Hi, thank you for your talk. I just have two questions about bumpidoic acid. Do we understand what the cost is gonna be, and sort of piggybacking off of that, do we have a sense of if it's gonna really be of any clinical utility with PCSK9 inhibitors, especially since oral PCSK9 inhibitors are in the works? So, we do, the cost has been up for a while, and I think it's around $10 a day with it, so that's still gonna be, what is that, 300 a month, 4,000 a year. It is additive to PCSK, it's been used with PCSK9, you can add it to PCSK9 inhibitors. We'll have the outcomes data, hopefully at the end of this year, the beginning of next year, and we'll find out is the, how does this study work, and one thing that's kind of nice is, this is the first trial, Martha, that actually has a high percentage of women, because there are women with statin intolerance, so it'll be interesting to see what we find, but your last question was about effectiveness in terms of outcomes, we won't know until we get that study data. Thank you. Great, well, we have still some other questions that people typed in, so we'll do a few more questions, just to make sure everybody who maybe doesn't wanna come up to the microphone, we get to your questions. So, one person asked, and this is, I like this question, so I'm gonna ask it, why is there no push for a polypill with low-dose aspirin, atorvastatin, and an ACE inhibitor in high-risk patients? Are we doing a disservice? Anyone have an opinion on that? So, I think the issue with polypill, first of all, is a lot of our guidelines say don't use aspirin, so that's a mistake with the polypill, but there is a fixed-dose combination of ezetimibe and rosuvastatin available, along with ezetimibe, another one with atorvastatin. There's a fixed-dose combination of ezetimibe with every statin. In the U.S., though, it's available, no, just, no, in the U.S., only those two are available. They make it for every statin. But not in the U.S., only the U.S., the only fixed-dose available in the U.S. with ezetimibe is with atorva and, no, Simba, I don't think it's even, Simba was there, but you have atorva and rosuva. There's not one with prava. There's not one with cereva. Yeah, you still have it around. Yeah, it's still around, strangely enough. Any other? No, I agree. I think aspirin issue has not been settled, so why use a medication where we're not sure on that? And I think it's a question of what approach you want to take, even if you take aspirin out. Some people take the approach of treating at the population level, bring the entire population's blood pressure down by five millimeters and LDL cholesterol down by 20. That's one approach. I'm not saying that's a wrong approach. That's one approach. The other approach is you take individual risk factors. I think in U.S., we are more accustomed to that kind of mentality. In some low-middle-income settings, that might be the best approach if you're gonna take a population-based approach. But aspirin will be an issue with this. I have a follow-up from that. What if it's a secondary prevention patient, right? Then it's aspirin issue sort of goes away, you think? No, because there are some patients who are dropping the aspirin in favor of a different P2Y12 inhibitor. Do you have a question? Yes, U.S. guidelines for high-risk patients generally target 70 milligrams per deciliter. The Europeans, 55 milligrams or 50. What do most of the panel members target? Well, you know, that's, the U.S., it's a little bit, it's a threshold. So if you're over 70, you add something, and I think what you would look at is, well, what, maybe the different question is, what is the optimal LDL? I think the optimal LDL is probably around 35, 30 or something, I mean, and that's, and for high-risk patients, based upon the ODYSSEY outcomes and, you know, the other study. Doesn't mean I'm gonna try to get there for every one, but it, I mean, that would be ideal, and that's why a threshold, you have the liberty of you deciding, well, it's over 70, but do I wanna get to 50, do I wanna get to 40 or 30? You can kind of dial in your treatment. Yeah, because I think in an ideal world, I would love everyone's LDL to be 30, but I know that the more medication I use, the more side effects I'll give to the patient, and there's drug-drug interactions and things, but if everyone could get there easily, safely, without side effects, I'd be so happy if everyone was 30. And as we all showed, so many patients, we don't, how few patients we get to under 70 is, you know, let's just get there, and then we can get on to the other levels. I think that's the problem. Exactly, I think I can give you a perspective. The U.S. guidelines took that approach, because if you look at the enrollment, it's a more pure approach. The enrollment criteria for PCSK9 inhibitors were 70 of LDL cholesterol, non-ADL cholesterol above 100, so that is the approach that was taken there. Is that am I, Dr. Ballantyne showed you, right? 69 or close to 70 was statin, and 54 is what you got from the use of the combination therapy, so that's the approach the U.S. guidelines took. Europeans took an approach, which is more of a biologic approach, lower the better, so they set a, they actually set a target. U.S. guidelines set a threshold, as Dr. Ballantyne said. The other thing you should keep in mind is that the relative risk may be the same, but the absolute risk reduction is gonna go down as you bring somebody down from 70 to 50, 50 to 30, so just keep that in mind, what you're seeing here are relative risk reductions, but on the absolute scale, you're doing pretty good if you get down to 60, right? Sure, 40 is better, but how much absolute reduction you're gonna get is going to go down as you go down that lane. Great, well, another question that is asked, I guess we sort of answered it, is how low is too low? So we'll skip that. Okay, another question, would you use bamphidoic acid in patients with a history of gout or patients with a history of core, I just think a history of gout, I don't understand the rest of the question, but. So, you know, one thing that's important, it's really the baseline level of uric acid, so if you have someone who has a history of gout, they're treated with allopurinol, and they've got a normal, low level of uric acid, they did not have increased risk. So it's the issue is, when you see that, check the uric acid. Now, if the uric acid is high, now you have somebody, you gotta think twice, you certainly gotta monitor it. If you use it, it goes up further. But it's the baseline level of uric acid. Obviously, with a history of gout, you're tuned in to look at that and watch it carefully. I would, if it's elevated and they've got a history of gout, you need to think twice about, you know, is this the right agent for this patient? If you do use it, make sure to monitor the drug. Great, and I wondered if anyone knew the cost of bempidilic acid, because there's quite a few questions, actually. Okay, he said $10 a day. All right, perfect, sorry, I missed that. And then, in the logarithm of the management of atherosclerotic cardiovascular disease, where do you put in glycerin? There is an ACC pathway that will be coming out very soon, and it's gonna cover in glycerin and bempidilic acid, so be watching for that. It's gonna also include an update about how does calcium scoring, because this whole issue of extensive subclinical atherosclerosis, so it'll have a little bit more detailed information in terms of that. All right. Sorry. We're supposed to end now. Yeah, so we're just gonna wrap up now, actually. I was just making sure there was no other last question that people really had burning here. So I'd like to thank all my speakers here who did an excellent job. They're the leaders in Lipid, so I'm so happy that I could even share the stage with them. To our fellow-in-training, Anam Saeed, who did a great job at making these cases, and we're gonna make them available online as well, because we didn't even get through all of them. And I'd like to thank our audience for coming tonight and being with us, and hopefully you'll get time to meet with the speakers at another time throughout the meeting. Thank you so much. Great questions and discussion.

ASCVD

lipid-lowering therapies

statin intolerance

PCSK9 inhibitors

polypill

LDL cholesterol levels

treatment approaches

high-risk patients