Chapters Transcript Video Updates in Lipids Click here to view presentation deck Back to Symposium My name is Doctor Yusupov. Uh We'll be talking about updates in lipid management. Um For many of you who are in primary care, you guys, uh this will be just kind of like an overview, but there are certain things that um hopefully, uh you'll get out of it and, and, and enjoy. So I don't have any disclosures and I like to start my talks with a quote. So this one is from Benjamin Franklin. Uh as you all know, an ounce of prevention is worth a pound and cure. So, uh what we'll talk about today is what is the importance of statin adherence when statins aren't enough? What do we do? What can we hope to achieve with some of uh with some of our friends? Uh Zetia P CS K nine inhibitors and uh bedo acid. And hopefully we'll have uh just enough time for a brief word on um LP Little A. So cardiovascular disease is uh is on the rise. Of course, this is a multifactorial uh in part from a longer life expectancy increases in obesity increases in ultra processed foods, but also at least in part due to uh inadequate cholesterol management. So um in this uh International Atherosclerosis uh society position paper, you know, uh what we can see is, you know, basically what they took together was from all of these studies that took uh that looked at LDLC lowering uh through various different uh methods. And in these studies, um based on patients LDLC ratios, percentage of um uh cardiovascular disease, uh revascularization stroke was, was higher. And this is not a surprise to, to any of us. So we know this uh very well and probably nothing is as well studied in cardiology as the association of of elevated LDL and elevated lipids. And uh and, and mace uh in the Gould us registry of patients with a CBD receiving lipid lowering therapy. LDLC tracked over two years indicated that two thirds remained over 70 mg per deciliter. So we know how dangerous uncontrolled lipids are and how uh dangerous uh uh LDLC levels are. And yet, you know, we struggle with our patients to get them under the level uh that, that we would like them to be. Um how well studied is this. So, uh in this uh uh in, in this basically, in this uh me analysis that was put together by the cholesterol treatment trialist. Um uh over with over 90,000 parti participants from over 14 randomized trials. Uh You can see that the treatment groups had significantly better outcomes when it came to non-fatal. Uh M I um uh and and cardiovascular disease and death. So there being an approximately linear relationship between the absolute reductions in LDL cholesterol achieved in these trials and the proportional reductions in the incidence of coronary and other major vascular events. So something to tell your patients and something that, you know, I try to remember to tell my patients that, you know, uh for every uh basically 40 mg per deciliter reduction in LDLC that we get, there's a 20 to 25% reduction in mace. And that's huge, you know, looking at the, uh you know, overall uh population that suffers with hyperlipidemia. So why is it here and so important? You know, because a lot of times, you know, we'll see our patients, we start them on atorvastatin 20 for example. And we're like, hm, we're not getting the lipid lowering effect that we were hoping for. Let's give them 40 let's give them 80. But the question is, are they adherent? It's not enough to just prescribe a high intensity statin, we really need to know. Well, hey, are you taking it because, you know, according to this study that was done. And I thought that this is a really uh really cool and useful information. Uh But basically, uh what you see here is that you'll get better um uh um hazard ratios with adherence to a low intensity statin than non adherence to high intensity statin. You'll have better changes in your LDLC with adherence to a low intensity statin, the non adherence to a high intensity statin. So it's not just what we're prescribing. It's, hey, are, you know, are you taking it? Um So, you know, with this data, you know, we know this data and our patients probably, you know, we educate them, they know this data. So every single patient wants to be on a statin. Right. Exactly. Right. So, um unfortunately, uh this is uh I, I thought a pretty elegant study that was done, um, uh over in, uh in Mass Gen and this is a retros retrospective cohort study conducted from January 2019 to December 2022. So, pretty recent, um, their inclusion criteria, you basically had to be over 18 years old and, and, and have a reason to be on a statin whether a high A S CV D risk score diabetes, uh you know, uh history of P ad et cetera. Um And what we can see is that, you know, a lot of patients for whatever reason, they, they don't want to be on a statin 21.9% initially did not accept statin therapy and 6% never initiated a statin therapy. Uh, even during their follow up. And these are patients, you know, going to Mass Gen Harvard trained physicians. And, uh, you know, and even then we see that uh actually, uh non acceptance of statin is, is actually higher in our, in our female patients, uh, than, than in our male patients. Uh, so despite all this data, and so what are some of the reasons? Well, there is true statin intolerance, you know, that, you know, some patients really are intolerant to statin and, you know, you know, and that's basically defined by, yeah, having an inability to take a statin despite lowering a statin, having had tried at least two different statin medications and still a patient is intolerant to it. Now, whether they're truly having effects due to the statin or not, may not be as important because if you tried your best and you've lowered a statin therapy and you started a different statin, your patients not taking it because of, you know, muscle cramps or, or whatever it is or, or, or, you know, whether the symptoms are real or perceived it, it doesn't matter because if your patient's not taking the statin, you as a provider need to, to find a way to, you know, to, to either empathize with them and, and, and find a way to get them on some sort of lipid lowering therapy. So there are some patients with that intolerance and there's patients that are completely intolerant, they just can't take it. There's patients that are partially intolerant, you know, maybe the patients will be agreeable to taking, uh, you know, a 20 mg atorvastatin every other day or every or every third day. And we even have data to suggest that that, that, that's better than not taking anything at all. I think we all know that part of the difficulty with statin therapy, especially in the age of social media that we're in is the nocebo effect. And the nocebo effect uh is perceived negative symptoms experienced by patients when anticipating a treatment to be harmful. And for whatever reason, statins despite being so effective at lipid lowering, they really get a bad rep. And I think a lot of our patients before they even take a statin, they're like my, oh, I heard from, you know, Betty down the block that I'm gonna have, you know, muscle cramps or I'm not gonna be able to go to the pool or I'm not or what's gonna happen to my co enzyme Q 12 levels or like, you know, am I gonna have like Alzheimer's because you're giving me a totin 10 mg and you're just like, whoa, you know, uh so that, that always kind of surprised me, but we know that it's real and, you know, there's a few really elegant trials that, that took a look at the nocebo effect. And I think that these trials are great, not because they tell us as providers, something that we already know about this nocebo effect. But I think it's something that we can go in and tell our patients about the nocebo effect and maybe kind of help arm them knowing, hey, this exists and maybe this is happening. So the two trials that looked at, this was, uh, the Samson trial and the Statton Wise trial, the Samson trial is such a cool trial. Basically. What they did was they gave patients three different bottles, one bottle had a statin, one bottle, had a placebo, one bottle, had a nothing. And, you know, they asked the patients to tell them, like, when are you experiencing symptoms? And there was no change in symptoms for when the patients were taking a placebo. And when they were taking a statin, when they were on no treatment, you know, it was better because, well, they knew that the bottle was empty. So the symptoms were less with the empty bottle, but the amount of symptoms were the same on placebo and on statin. So I thought that that's such powerful information to provide your patients. Um It's very difficult to do in your own clinical practice, but at least we have this information to tell them about it. Um Oops. Uh So some of the uh so I'm sorry, that's a little bit uh out of order. Uh So there is a true, you know, thing of some patients really do have a statin intolerance. Overall incidence is reported to be 5 to 30% in the literature. But true complete intolerance is estimated to be much lower, less than 5%. Um And I think a very important thing to, to tell our patients, you know, is that discontinuing a statin also carries a real risk, like I get it, you don't wanna take it and maybe, you know, you really truly can and your body really can't tolerate it and you are having really bad symptoms. But if we don't find a way to get you to continue taking the statin, there's also a risk involved in that. And so this study I thought was awesome. So, among 28,266 patients who, and these are patients who had like, you know, either side effects or some sort of intolerance to statins. They study them over time and they basically put them into two groups, patients who are willing to continue their statin and those who were not and discontinue their statin prescriptions. And you can see there's a huge change in all cause mortality between these two patient populations. So perhaps arming our patients with this knowledge can also help us, um you know, and if not convince them but, but work with them to, to get them to continue taking this, you know, really life saving therapy. So what are some of the strategies that, that uh that are available to us to uh to combating statin intolerance? Or we can switch the statin, we can do dose adjustments, we can do intermittent dosing, we can do alternate therapy. And I think one thing that I'd really like to stress here and something that, you know, II I talked to my patients about the biggest bang for our buck in a lipid lowering medication, especially a statin is when we first started. It's not that jump that we make from 40 to 80. It's that jump that we make from 0 to 10 that we get the best bang for our buck. And the biggest side effect that we get is from 40 to 80 not from 0 to 10. So, you know, it might be who has to, to say, ok, well, you know, you, you, I the guidelines say you should be on 40. You, you don't wanna take 40. How about 10? How about 10 every other day? You know, at least we're getting something and, and we're probably getting much more, we're getting much more than nothing but also much less side effect profile. Um So anyway, you have a patient, they're refusing, they can't or you have a patient, they, they're, they're on it and you're still not at goal. What are some of our other friends? So there's Zetia, uh the way Zetia works is uh basically, it um uh prevents uh cholesterol uptake by blocking the N PC one L one inhibitor that's a mouthful. Um And uh uh you know, it reduces your, your, your overall um uh plasma cholesterol levels that way. Um how much do you stand to, to benefit from uh from Zetia? So, um you know, in, in this uh made analysis of 2722 patients. So, the systematic review basically what, what you're looking at is somewhere between 15 and 20%. This made analysis calculated that your overall reduction from Zetia is about is about 20%. And, and we're gonna see that multiple times throughout uh the rest of this uh this talk, which is not nothing that is still a very significant amount. What about Zetia combination therapy? So you have a patient that's already on a statin is Zetia gonna give you anything? So, in patients that are already on a statin, if we start them on Zetia, we can expect to get about another 10 to 15%. Or as this study uh or is this made analysis showed by, by doctor you and colleagues that uh you're, you're gonna get about a 13 13% reduction. And LDL um So what if that's not enough or if you wanna kind of jump ahead and you wanna go to the, to, to the next uh to the next uh stage. And so that's gonna be really our P CS K nine inhibitors. So the way P CS K nine inhibitors work is basically um you know, uh P CS K nine, when it binds to an LDL receptor, that LDL receptor will then get degraded by, by the cell by, by the body tissue. And that's one less receptor to remove cholesterol from the bloodstream. So, by inhibiting uh P CS K nine, you're gonna have less of them. Uh you know, floating around or, or, or basically less of them blocking your LDL receptors whose job it is to, to uptake uh these uh uh lipid molecules. Um So how good is uh is P CS K nine? So this takes us uh to, to some of the trials. So, uh the Gaus trial, basically, this looked at patients um uh with intolerance um uh uh to statin uh agents. They were randomized in a 2 to 1 fashion with either um uh Evolocumab 420 subcutaneously every month or Zetia 10 mg. And so what do we see? So the yellow, the yellow column is our Zetia reduction. So, like I said, you're gonna, you get about 15% reduction. This study showed the same in Gauss three, that Zetia is gonna give you about a 16.7% reduction in LDL. But Evolocumab gave you a 52.8% reduction. So you have a total difference between Zetia and evolocumab of 36% which is uh which is a very significant huge reduction. You're talking really being able to get some of your patients LDLs down to, to that below 50 goal. If you, if you have patients with really high A CV D risk scores, uh Also there's the four A trial. So the four A trial, they didn't compare it against Zetia, they compared it against the placebo. And so once again, you're seeing about a 50% reduction in UL AAB. Uh and then if you look at the primary effi efficacy uh end points, you're talking about like an absolute risk reduction from their primary end points of about 2%. And you're talking about uh from their uh key secondary end points also uh of uh the, the same about 2% less in incidents. Uh So what are some things that we should know about P CS K nine inhibitors? So we can tell our patients before we start them or if you know another physician is starting them on your patients, then they come back to you. Uh What can you expect? So, uh the most common side effects are, are cold or flu like symptoms. Uh You can get some pain or irritation at the injection site. Uh You can still get muscle pain and I, I don't know if that's true muscle pain or if everybody just now associates cholesterol lowering with muscle pain. But, but that is uh something that, that is common enough to, to let your, let your patients know. What's the other cool kid on the block? Uh It's uh benic acid or the new kid on the block. Uh It's an oral medication. It's not an injectable, it's a once daily, it's liver specific, it has a half life of about 24 hours. And uh this works on the same pathway that, that statins work. But statins work on the H and G coa reductase. This works on the adenosine triphosphate citrate lia, the AC L uh inhibitor, not the orthopedic AC L. This is uh this is a different ones for primary care and for cardiologists here, uh different AC L therapy. Uh And so, by blocking it, you're essentially um uh you know, get, getting uh reduced uh LLDLC levels. Um The big trials that looked at bedo acid were the, were the clear trials, uh the clear harmony uh trial. So with a maximally tolerated statin, the BPA acid uh had AAA placebo corrected reduction of 18.1%. Uh The clear wisdom trial maximally tolerated statin 17.4%. So this is with already a maximally tolerated statin, you're getting, you know, another 15, you know, about 15% uh in patients who are statin intolerant, you're getting a 20 you're getting a 23.6% reduction or 21.4% placebo corrected uh reduction. And then with Zetia with statins, you're getting a 28.5% placebo corrected uh at, at, at 12 months. So patients who are statin intolerant, the best bang for your buck that you get with benic acid is when you combine it with Zetia. We've seen that, you know, Zetia combined with benic acid does, does better than Zetia alone, it does better than bedo acid alone. And so in your patients who are starting intolerant who maybe are refusing to take an injection, you really want to get that, that LDL down, that combination of beed acid and, and Zetia is good. But how good is, you know, kind of throwing, uh I guess the Hail Mary, right? Throwing almost all the orals at a patient. So this study looked at, if you give patients all the three major uh lipid lowering oral tablets, you can look at approximately 63.6% uh reduction uh by using a triple therapy, uh lipid lowering agent. Uh What are some of the side effects of BMDO acid? So, in these patients, the big ones that, you know, there, there's quite a few and this is from, uh uh from the trials that looked at beed acid. But the, the ones that I really wanna highlight are hyper ethem gout cholos. These are definitely the, the, the big three that you wanna uh forewarn your patients or if your patient has, uh a patient, uh, a history of cholet or, or cholecystitis without having their, you know, uh gallbladder removed or history of gout or history of hyperuricemia bedo acid is not, not the medication for, for that particular uh patient. And really quickly, I just have one or two slides on LP Little A. Um, you know, uh the LP Little A has been getting a lot of, a lot of attention lately. How do we use it? What does it mean? Well, what we learned from the Odyssey trial is that patients with the highest levels of LP. Little A were at the greatest risk of mace and they're the ones that benefited the most from LP. Little A reduction. So, what does that mean? So, the way I take that is that I don't, if a patient has no other risk factors, they have a completely normal A S CBD and they just have an isolated elevated LP. Little A, I don't find that enough for me to necessarily start them on any therapy. I think it's enough for me to, to tell them, hey, you have this, hey, we need to keep an eye on this and hey, down the road, if you develop any, any risk factors, we're gonna aggressively move to treat your, your overall uh cholesterol and, and uh and lipids. I also use it if I have a patient, young person comes in history of stroke or history of an M I at a young age or really severe family history. And I have a high LP Little A, I'm, I'm just going straight ahead target LDL goal less than 50 like aggressively right away, especially if they've already had any form of mace. Um There's really a lot that still needs to come out as far as how we're gonna use LP Little A. Some people use it as like a secondary risk factor. So, you know, those patients that are kind of like intermediate A S CBD 5 to 7.5 should I start a statin? Should I not start a statin, you know, there's uh literature that's to say get a calcium score, get a high sensitivity CRP if those are elevated, treated as if it's, you know, in that intermediate to, to higher risk. So some people use LP A in the same way. So if your CRP is negative, your calcium score is negative, but the LP A is, is high. I've seen some physicians use that as like a trigger enough to kind of uh to bump them up into that into that treatment zone. So, uh you know, this is the, the guidance regarding uh LP Little A, I'm not, I'm not gonna go into it, but basically uh uh patients for you 75 with a 10 year 7.5 to 19.9 having elevated uh LP Little A is a risk enhancing factor. And that's, and that's kind of like the way that, that I use it that it, it's, it's essentially a risk enhancing uh uh a factor uh that, that we have for right now. So in summaries, um you know, uh we start with the moderate intensity statin, you get 30 you know, about 30% a Zetia beo acid, about 45% high intensity statin, 50% high intensity plus Zetia add on another 15% to that. Add on Benedick Acid. The triple therapy of orals, you're getting 65% P CS K nine, around 50 to 60% uh statins you're getting uh and the P CS K nine, you can really drive down that LDL. I mean, I've had patients uh who have had like cabbages at like, you know, 50 with their initial like LDL is like 200 you put them on Zetia P CS K nine and, and a statin and in follow up it's like 34 like, like you can see some really, really amazing crazy stuff. Um So anyway, this is the expert consensus therapy. I know I'm running short on time, but if you guys ever have uh any questions or if there's any way that I could ever help answer any questions regarding lipids. Uh You know, I, I primarily I'm an, an imager, but a preventative cardiology has always been one of my passions and uh I really wanna just help you guys in any way and I would love to work with any and all of you. Uh Please direct any questions to me. Uh Thank you. Published November 5, 2024 Created by Related Presenters Denis Yusupov, MD Cardiology View full profile
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