Welcome back, everybody. This is going to be the last episode here where we're breaking down the 2026 ACC AHA disability bank guidelines. If you've Seen all of them so far? Congratulations. You probably know more than 95% of people when it comes to lipids. If not, if this is your first one, I got more. Go look at those things. But briefly, if you haven't been there before. We're talking about all the changes here. How we're no longer looking at percentages. We're trying to drive to absolute targets, like driving LDL below 55 for our highest risk, 70 for our slightly less risky patients, and then 100 for everyone else. We've talked about the prevent calculators, how they're totally different. We talked about CAC scoring, lipoprotein delay, lots of things. So we know that there are lots of changes here, and we have lots of more information on that. But today, we're focusing entirely on pharmacology and the expanded toolbox that we have to help our patients reach these new goal targets. So, let's dive straight into it. So, even with all the new tools we have, satin still remains the bedrock of what's recommended in these guidelines. And so, Having a good understanding of these will be very, very helpful for all the conversations you're never really going to have to have. So, first, let's start with the mechanism. Statins competitively inhibit HMV coloreductase. And if we remember from med school, that is the rate-limiting enzyme in how the liver makes cholesterol. So, when you stop that synthesis, the liver cell realizes, hey, I'm low on cholesterol, then responds by up-regulating LDL receptors on the surface of the cell. Then the liver acts like a vacuum, just pulling in all those lipoproteins, right? So, specifically LDL. From the bloodstream due to increased LDL receptors, and that's going to be a common theme. We have more LDL receptors, then we're going to have more cholesterol brought in, and then theoretically a lower LDL. So, that's what's happening with these statins. And there are also a ton of different statins. If you look at this chart here, these are two charts taken directly from the guidelines. I want to talk about it, but there are different ways, and there's different dosing options. There's just so many things. And on the right side, you can see all the statins that are approved, and there are different Particular dosing regimens, right? So you can look through it. I don't necessarily need to say that. You can look at the chart, but we talk about we have atorvostatin, fluvostatin, lovostatin, patavostatin, pravostatin, resubostatin, simostatin, All these different statin medications, right? And on top of this, you know, we have so many. How do we divide them up? Well, there's multiple ways to divide up these medications, but the most common one is based on their intensity or how much we expect them to lower LDL. So, we'll start with the high-intensity statins first, which are expected to lower LDL by 50% or more. So, when someone says high-intensity statins, that's what they mean. They say, hey, we expect LDL to go down by 50% or more. And these are Torvastatin 40 and 80 milligrams, and Rosuvastatin, 20 and 40 milligrams. Next, we're going to talk about the low-intensity statins, because if we know the high-intensity and the low-intensity, everything else is a moderate-intensity statin. That's how it goes. Low intensity should lower LDL less than 30%, and moderate intensity would lower between 30 and 49%. In the low intensity sentence, Are fluvostatin 20 and 40, lovostatin 20, pravastatin 10 and 20, and Simba statin 10, right? And everything else is in the middle. And there's a lot going on, right? So I just Put this on here because most people get the ones they're comfortable with, but it's something I wanted to talk about here just to make sure: hey, there are other options, and there's reasons why I would pick one or another, and we'll kind of continue to go on to that. Now, I wanted to discuss another way we can divide statins, which is whether they're hydrophobic versus hydrophilic. And this really isn't talked about too much in the guidelines, but I think it's important for us to understand this because it's a helpful way to break these down. And this distinction can be important because it can influence their absorption, metabolism, and potential for drug-drug interactions, as detailed here in Table Seven of the Guidelines. So, we'll start with some definitions, right? So, hydrophobic. Hydrophobic. These statins are fat-loving. So, hydrophobic can also be lipophilic. So, hydrophobic, lipophilic. Lipo meaning fat, philic means they love it. So, fat-loving statins, they readily dissolve in lipids. And the terms I said there were hydrophobic and lipophilic. Those are interchangeable, right? So the majority of the statins are lipophilic, which include a torvastatin, simvastatin, lovastatin. Fluvastatin and patavastatin. Most of these are also metabolized by the CYP3A4 route, and it's important to know that because many other medications also use that pathway. So, the big takeaway here is that when something is hydrophobic or lipophilic, they're more easily absorbed and can penetrate a wider range of tissues. Then move on to the other side, right? So the hydrophilic statins or lipophobic. And these are water-loving statins. And the two examples here are Rosuvastatin and Pravastatin. And unlike their hydrophobic counterparts, Pravastatin is not metabolized by the CYP systems at all, and Rosuvastatin only minimally uses the CYP. 2C9 pathway, and this reduces their potential interaction with other drugs. And these are less likely to be absorbed and penetrate a wider range of tissues because they're more specific to the liver. So that's kind of The breakdown there. And as you can see from this slide, every statin is a little bit different when it comes to how it works pharmaconetically. And that's why the guidelines recommend that if a person is not tolerating one statin, you can try another. So, a general approach that I can try sometimes, I'll do this occasionally, is that if you try a lipophilic statin and they don't tolerate that or it's not a good fit, then you can try a hydrophilic statin, as theoretically, it may have some differences. The data on this has not really been parsed out. It doesn't really show that that's necessarily the case. Meaning, yeah, if you go from hydrophobic to the other one, you're going to have differences. That's not necessarily the case, but ultimately, each individual patient is going to have. Different physiology, right? And so it's at least worthwhile thinking about this and just giving you an option for: hey, why would I choose one versus the other? And to me, I think it's kind of interesting. I didn't really learn about this, but that is a way to divide them that we can think about. And so now I'm going to talk about something that straight up is not in the guidelines, but I wanted to include it because it's so important. And I want you to have a comprehensive resource for when it comes to statin selection. So I'll talk later about statins and diabetes, but it is a well-known side effect of statins that they can affect glycemic control. And so, what I'm going to do here is I'm going to simply do my best to tell you what we know about which specific statin medications affect blood sugar the least and the most. I'm not going to give you like this one's the best, this one's worse, but there are a couple that tend to trend in certain directions. And so the statin medications that affect glycemic control the least appear to be pitavastatin and apravastatin. And the ones that affect glycemic control the most Are the high-intensity statins, a rosuvastatin and a torostatin. But really, the key here is that it seems to be dose-dependent. Trials have shown that high-intensity therapy produced a 36% increase. In nuance at diabetes versus 10% for low intensity or modern intensity. And so it means that much of the difference between satins really reflects their potency rather than intrinsic molecular properties. But if someone's very worried about this, then we can talk about: hey, what options do we have? And so when we prescribe statins, the number one thing is yes, we are trying to lower athergenic lipoproteins, that's for sure. But we found that statins also have What we call pleiotropic effects, meaning other positive effects that weren't necessarily the main intention or the reason we started them. We say, hey, they actually do these things. And it's kind of a Physiologic downstream effect from blocking the HMJ coloreductus. So, by blocking that pathway, we also stop the synthesis of isoprenoids, which are needed to activate certain intracellular signal molecules. And long story short, when we inhibit those pathways, some important things can happen in the vascular wall. Specifically, we can see restoration of endothelial nitric oxide, which helps those blood vessels relax, which we know is very important. On top of that, statins also drop localized inflammation, which is very important. They can also promote thick, stable fibrous caps over volatile lipid color. So they kind of stabilize plaques. So that stability is what stops the plaque from rupturing and causing a massive heart attack. Completely independent of the actual L number we hit. So that's why there's a couple different reasons why they can consider: hey, you're getting some additional benefits with statin medications that are on top of just lipid lowering. However, we all know the reality of prescribing statins. There will be patients that after you prescribe them, they will get side effects. That's very, very important here. And so I want to talk about both sides there. Yes, we have to be fair. We have to look at the pros and cons. So, the pros, we know they're cheap, they're accessible, they're generic, and they prevent major adverse cardiovascular events. Like, we know that that's pretty, pretty well understood. But we also have to be transparent and empathetic about side effects because experiencing them is the primary reason patients stop their medications, right? And the most common issue is statin-associated muscle symptoms or SAMs. For the patient, they typically present having symmetrical aching or weakness in the muscles. And even if their keratin and kinase levels are normal, their discomfort profoundly impacts their quality of life and it needs to be taken seriously. So, we also need to be mindful of GI upset, which can also be disruptive. On top of that, metabolically statins, as I mentioned before, can have an impact on glucose homeostasis. And in patients who are teetering on the edge of type 2 diabetes already, a statin might actually push their A1C over the line earlier and make them actually diagnosed with diabetes. Those are big things. And on top of that, we also have some severe toxicities that can happen. Any medication can have severe things. We have reports about this. It can cause liver injury or rhabdomyelysis, which, although they're exceedingly rare, we do have to mention so that patients are completely informed. And I'll go more into discussion points for statin side effects in the future, but I wanted to at least talk about these right now. Okay, so we just talked a lot about statins. Now let's talk about things other than that. So when they're not quite getting us there, if statins aren't doing their job fully. Or we have patients who can't tolerate them, we move down our toolbox, right? So Azetami is our absolute number one first-line add-on. So it works differently from Statins, and it works in the gut by selectively blocking the NPC one-on-one transporter on the brush border. It stops the body from absorbing cholesterol. That's kind of how I think about it. And because we're starving the liver of additional cholesterol, the liver, once again, upregulates LDL receptors and pulls more cholesterol out of the blood, therefore lowering the LDL. By itself, it's a kind of modest tool, maybe around 18 to 20%. But here's also the real trick, right? So, when you put someone on a statin, their gut often compensates by trying to absorb more cholesterol. Azetami then shuts that back door. So adding it to a statin gives us a 25% decrease on top of that as well. And so they kind of work synergistically. You're decreasing production. And also absorbing it. And so, when it comes to side effects, though, Zetamide is really safe and well tolerated. In clinical trials, its adverse effect profile is often indistinguishable from a placebo. So, it works really well. You maybe will hear about gastrointestinal upset, maybe some diarrhea or fatigue, but that's pretty rare. However, there's one important caveat we need to keep in mind when we combine it with the statin, which is how we use it 90% of the time. There's a slightly increased risk of persistent elevations. In transeminases, right? So meaning LFTs over three times upper limit normal. It's still a rare occurrence. And the guidelines do recommend explicitly keeping an eye on those liver enzymes before and after initiating combination therapy. So that's kind of like if we're on both, we want to keep an eye on that. And that's what's going on there. Next, if you have a patient who we've tried it, definitively can't take statins, right? We've tried the thing. So, right, the statins, usually we try one. If it doesn't work, you try a different one. If you can't do two, then we say, yep, like you are officially not there. Or if they have a severe reaction to one, we say no. But we've tried the whole D challenges and re-challenges, and they just can't do it. This is where this next one comes in: bempidoic acid, and it can be a really good option. It works upstream of where statins work by inhibiting an enzyme called ATP citrase lyase. And the coolest part of bembadoke acid is actually a prodrug. It only turns on when it meets a specific activating enzyme, and that enzyme is highly concentrated in the liver but completely absent in the human skeletal muscle. This means we get the hepatic cholesterol suppression we really want without the muscle symptoms. So that's really, really huge. And there's also been outcomes data showing this as well. That it leads to fewer cardiovascular events. So, we expect about a 20 to 25 percent reduction in LDL as a monotherapy. However, we also Have to make sure patients are aware of risks, right? It competes with uric acid in the kidneys, so you will see serum uric acid go up and it can trigger gut flare. There's also a known, albeit rare, risk of tendon ruptures, which, especially if they're older or on fluoroquinolones, can be bad news. And as a sports medicine doctor, that makes me very sad. I don't want to have a tendon injury after prescribing a medication, but something we can think about. And on top of that, you can also stack this with statins. So, we've talked about statins. You can add on azetamide, you can also add on mempidoic acid. That works as well. And for our highest-risk patients or those with familial hypercholesterolemia, or you know, have really high risk, and we need to get them down low. Sometimes we mean even more, and that's where the heavy lifters, the PCSK9 inhibitors, come in. Usually, the PCSK9 protein binds to LDL receptors and tags them for destruction. Right. So that's what happens. We say, hey, yep, PCSK9 helps degrade the LDL receptor. These monoclonal antibodies, specifically evalocrimab and alarmocromab, those are the names of them, they act on this PCSK-9 protein by binding to it. So the LDL receptor can't be destroyed. As a result, these LDL receptors stay on the surface of the liver cell and recycle dozens of times, massively clearing out circulating LDL. And their potency is pretty much unmatched. We're talking about. An additional 45 to 64 percent drop on top of whatever the statin is doing, right? So we have a big one, and so we have lots of data showing there. Very, very effective, and they also can prevent heart attacks as well. The downside, well, we're dealing with injections, right? So, either bi-weekly or monthly injections, which for some people they don't want to do. And the reality of navigating probably a prior authorization, which can also be a huge sticking point for a lot of people. From a clinical side effect standpoint, they're also remarkably well tolerated. So the most common issue you'll see are mild injection site reactions, redness or swelling. And there are other ones, though, more rare ones, but we see hypersensitivity reactions like angioedema. One practical pearl straight from the guidelines as well is that some of the Evilocrimab single dose pre-filled syringes contain a latex cover. So always screen for a latex allergy before prescribing these. Whereas Alarimocromab, those products are completely Latex-free. Something to think about, something I learned reading the guidelines here. And finally, despite some early noise in literature, it doesn't seem like they have any increased risk of neurocognitive issues, although that's what they saw initially, but they didn't see that. And as a quick aside, while we know the injectables are a barrier for many patients, it's worth noting that oral small molecule PCISCNI inhibitors are coming down the pipeline, right? So they aren't in the 2026 guidelines. Because the data is still maturing, but they are showing big promise that have huge results in terms of LDL lowering, but not in the form rejectable, which could be huge. And so now we're getting into the truly futuristic stuff that is becoming clinical rally, which is kind of crazy. Enclyzerin is a small interfering RNA therapy. Instead of using antibodies to mop up the PCSK9 protein in the blood, Enclyzerin goes directly into the liver cells, hijacks the cell's own machinery, and shreds the mRNA blueprint for the protein. So it stops PCSC-9 from ever being built in the first place, which is pretty crazy. LDL reduction is right on par with monoclone antibodies about 50% as well. But the biggest game changer here is the adherence profile and dosing. After a loading phase, This is given once every six months. It turns lipid management into something resembling a biannual vaccination we handle right in clinic. And the jury is still out in terms of the massive long-term cardiovascular outcome trials. We don't have that. It's still maturing, but the lipid lowering effect are pretty solid. When we talk about side effects, very similar to other PCSC9 in terms of they're very well tolerated, but most common things you'll see are injection site reactions. Maybe you'll see Redness, pain, or rash, and once again, could always have hypersensitivity, including angiodema, but that's also uncommon. And overall, safety profile makes it look like it's a right option for a lot of patients. And it could be cool, but it's not really common yet, and we're probably going to be reserved for prior auth and cardiologists. I have not been able to do it in primary care yet, but Something that was coming down the pipeline. Next, let's talk about bile acid sequestrants. These are oral agents that offer a unique and non-systemic approach to lowering cholesterol. Their mechanism is quite clever. They work entirely within the gut, binding to bile acids and preventing them from ever being reabsorbed in the body. This forces the liver to pull more LDL cholesterol from the blood to make new bile acids, which effectively lowers patients' LDL-C. And because they're not absorbed systemically, they don't have the systemic side effects associated with other lipid-lowering drugs. And agents you might see like cholestyramine is the big one. They provide a modest LDL reduction, anywhere from 10 to 27%. And this makes them a valuable option as an add-on therapy for patients who need additional LDL lowering on top of their other medications or those who can't tolerate statins. Notably, though, because they are not absorbed in the bloodstream, they are considered. Safe option for managing high cholesterol during pregnancy and lactation, which is interesting. However, their use is often limited by their drug bias. The most common issues are gastrointestinal side effects like bloating, constipation, which can be a major barrier for patient adherence. And on top of that, crucially, these, for whatever reason, can actually increase triglyceride levels. So, therefore, the guidelines clearly state that they should avoid them in patients who have elevated triglycerides, specifically 300 or higher. And so, bile acid sequesters are a useful tool potentially in our arsenal, especially for patients who need add-on therapy or during pregnancy. But we have to be mindful of the GI upset. This is not very common. These aren't like the most common ones you see out there, but it is an option that we have, and at least worth mentioning. Now, let's look at the math behind our prescribing choices. We need to be precise how we lower these LDL to try to get our targets, but there's one important thing we have to understand. One major pitfall is that when we think about Static medications, when we prescribe them, we think, hey, if I'm on something and I double it, I'm going to get twice as much lowering of LDL. That's not the case at all. There's actually something called the rule of six. So, for example, if a patient is on 40 milligrams of the torvostatin, simply doubling the dose only yields about a 6% further drop in LDL. However, that dose escalation significantly increases the likelihood of statin-associated muscle symptoms or other side effects. So, rather than reflexively pushing the statin dose to its absolute limit, the guidelines emphasize combination therapy to target multiple pathways. In fact, If you know a patient who has a massive gap from their baseline LDL and their goal, it's completely reasonable to start dual therapy, like a statin anazetamib right out of the gate. Adding Zetami, as we mentioned before, to a moderate intensity or high-intensity satin gives us another 25% drop, allowing us to achieve up to 65 to 75% reduction overall. And if we need to go even further, obviously we know PCSKN9 inhibitors, all that stuff. But it's for this very reason that lipidologists are now starting to recommend that we start with two low-dose medications like a lower dose stat and azetamide. These aren't quite in the guidelines yet, but it's coming. So, Loto statins have much fewer side effects, but we get the majority of the LDL lowering even at their lower levels, which is wonderful. And so, as I mentioned, not in the guidelines, but something that's coming down the pipeline, kind of like how it's. What we do now is with hypertension, we start multiple medications. It's the same concept and it's coming, but just be aware of that. And so now let's talk about the elephant in the room again: statin-associated muscle symptoms or SAMS. And so, this is the number one reason people stop their meds, as I talked about before. But section 4. 2. 11 gives us a map to kind of navigate this. We have to separate the uncomfortable from the dangerous, right? So, this is a controversial topic, but True myopathy, actual weakness with sky high CK or rhabdomyolysis, both are exceedingly rare, exceedingly rare, but they can happen. What we usually see, though, are subjective myalgias, achy shoulders, sore thighs, normal lap. Now, we know with statins, there's a huge nocebo effect here. So, if you expect a drug to cause a certain side effect, you have a high risk of having that happen. That's like very well known. But we have to remember. That pain, regardless of whether it's coming from nocebo or not, is very real to patients, regardless of the pathophysiologist. So, we have to be aware of risk enhancers as well. So, older age, lower BMI, and especially patients on multiple medications are at higher risk for SAMS as well. So, how do we handle this clinically? Well, first, we validate their experience. We never dismiss them, but we also gently have to have the conversation of: hey, risk benefits that, hey, if we stop a medication. Then there is a possibility that download bad stuff may happen. We're not trying to scare them. We're just playing this back and forth. And what they recommend is using a trial and error approach. So we do a de-challenge, stop the statin for a few weeks, see what happens. If their shoulders still hurt, Maybe it wasn't the medication. Maybe it was something else. If the pain goes away, though, then they say, okay, we might need a re-challenge. And they say, maybe from here, you try a different class of satin. You know, that's, they don't say that explicitly. They just say, try. This is kind of my recommendation here. Try a different class to see what happens, or maybe even drop the dose to twice or three times per week. If they truly fail that re-challenge, though, then we don't just throw up our hands and say, Oh, that's it. Well, then we move on, we pivot to our non-statin tools and keep them safe. And so We can talk all day about this, whether it's like, oh, should we do this or not? That's what the guidelines say. We have lots of other tools, lots of other tools in our tool belts. One thing you'll also see is you'll inevitably get asked about CoQ10 for Muscle Lakes. That's a big thing. So. The biological theory here is actually pretty sound. Statins block the pathway that makes cholesterol, but that same pathway also makes CoQ10. And we know that statins deplete it, and since CoQ10 is crucial for mitochondrial energy. It makes sense that if we lack it, maybe it could cause muscle fatigue. But here, unfortunately, is where we have to look at the outcomes and mechanisms and say, ah, it may not work out. What we realize is when we put this to the test in double-blinded. Controlled trials, randomized control trials, is the CoQ10 supplementation. It largely fails to beat a placebo for relieving statin X. And so, because the evidence isn't there, the guidelines do not recommend adding on CoQ10 for routine use. However, if a patient really wants to try it, I don't like stopping them. I'm like, okay, yeah, absolutely. We can make sure they're informed saying, hey, this may or may not work, but overall, pretty low-risk thing and take, so I personally don't care. I just set expectations that it may or may not help. But if they do do that, you have to understand if they're on Warfrin, which not a lot of people are anymore, but we have to watch like a hawk because it can mess up INR. But the guidelines say, hey, we don't formally recommend it. That's just something that's a Jordan Ranichism. And the final section of the document is all about navigating the messy middle of clinical practice, right? So every time we prescribe these meds, we're doing a risk versus reward calculus, right? In the guidelines, we're mandated to have an open, shared decision-making conversation with our patients about what we're aiming for and what the potential road bumps might be. And a couple of the big ones here. The first one is that those age 75 are older. In the past, there was a lot of hesitation to treat these votes aggressively. The 2026 guidelines are clear. Age alone is no longer an excuse to leave someone without a medication if they want it. So we look at the whole person, right? If they're functionally robust and have a life expectancy more than a couple years. You can treat them, it's reasonable. We also want to actively deprescribe if they're functionally declined, have a very short life expectancy less than a year. We want to get them off medications as well. And they say it's probably not worth being on a statin as well. And so, we want to protect quality life regardless of the age, but 75 is just once again going to be a kind of risk-based discussion. And a couple of things we want to talk about here. That causes anxiety for a lot of people are pregnancy and liver, right? So, statin and pregnancy absolutely do not mix. Cholesterol is vital for an embryo to develop And the guidelines are clear. Stop the statin one to two months before they even try to conceive. If we absolutely have to control lipids during pregnancy, we can use bile acid sequesters like we talked about before because they stay in the gut and don't cross the placenta. However, regarding hepatic safety, it's kind of interesting here. Both patients and older clinicians carry a lot of preconceived notions of, hey, I need this is going to hurt my liver. And the data doesn't seem to support that. Mild transaminase elevations happen in about 1-3% of people. And that's true. It's typically an adaptive reversible effect, not liver necrosis or long-term. And because severe injury is so exceedingly rare, the guidelines actually have officially stated they don't recommend, like, we do not routine scheduled liver enzymes on asymptomatic patients anymore. As I mentioned before, if you're starting a zetamide, that may be worth looking at as well. But if they have symptoms, we absolutely want to check. But starting a statin, you don't necessarily have to get the baseline enough teasing go from there. You can, that's totally fine, but they say you don't necessarily have to do that, which can kind of be interesting. And so, on top of that, we also have severe statin toxicity in some patients who have different medications, right? That can happen. A lot of times, it's usually from secondary medications, but we have to think about that. The biggest culprit here is usually The CYP3A4 pathway, as I mentioned before. If patients are on simvastatin or lovostatin and you give them clarithromycin or an azole interfungal, the statin stops breaking down, builds up in the blood, and can lead to increased muscle breakdown. That's what we can happen. On top of that, we also have to watch the transport proteins in the liver. And this is why we never ever mix gem fibrazole with a statin. It traps the statin in the plasma. And once again, you get high, high elevations. If you need to fibrate, You need to use fenofibrate with a statin. So, I have to talk about that. And then, other common medications like amuodarone or deltaizem also have to look at the statin dosing, we have to kind of cap that. And so, the easiest workaround for most of us is to use the chart, right? So, look at the chart. Kind of check drug drug interaction, see what's going on. Switch them to rosuvastatin or pravastatin if they have other medications that are on CYP3A4. Talk to your local pharmacist, that's always going to be the best answer if they know way more than us. But just Mentioned as well, the biggest reason why people have like long-term or big muscle symptoms in terms of like myopathies or whatnot, and a lot of times it's medication-induced drug-drug interactions. And another concern that we'll hear a lot is: will the statin give me dementia? So, it's a very common and understandable fear driven by FDA case reports of people talking about some sort of cognitive complaint. It has been investigated a lot, though. So, the reality confirmed by long-term systematic reviews and outcome trials is that there's no increased risk of clinically diagnosed cognitive decline like dementia on any of the lipid-lowering therapies. When they worry that, hey, we need cholesterol in our brain, we're starving the brain of cholesterol, well, we can reassure them that the brain actually produces its own cholesterol behind the blood-brain barrier. And in fact, we should also frame the other conversations saying, hey, is it actually doing good? By treating dyslipidemia, are we preventing microvascular ischemic changes in the future? Are we preventing silent strokes that may damage the brain, lead to vascular dementia? Something to consider. However, once again, patients are allowed to feel what they feel. And if they do have brain fog, we need to acknowledge that, right? You can't just say, oh, like it's nothing, it's the medication. Well, for them, they have it and they experience it. And so. We can do the same thing like we would with muscle symptoms. We can either try a different statin, move them on to something else, but the data doesn't show that like actual diagnosis of dementia, like that's not happening. It doesn't seem to be that's the case. The brain fog, they're not necessarily looking for those outcomes. So it's not as well studied. And so we kind of take it on a case-by-case basis. Another huge objection we face is, once again, we've talked about this before, but diabetes. We don't want to dismiss this because there is a grain of truth here that gets kind of warped on the internet. So, statins do impair how our cells take up glucose, which can bump the A1C up a little higher. But they don't magically generate diabetes out of thin air, right? So, in a perfectly healthy person, like if you're on a statin other than their cholesterol is high, if you start them, like they're not developing diabetes, it's usually the people who are pre-diabetic, right? So. A statin might push them over the diagnostic threshold a few weeks earlier than they would have crossed it naturally. A great land that I heard is that people who developed diabetes from statins were one snicker bar away from it, anyways. And so, it's not to make light of it. It's very serious, but it's not as pervasive as the internet makes it seem that, like, oh, these people are just flipping in the diabetes. The guidelines tackle this head-on, and they say the absolute restriction on preventing a fatal heart attack. outweighs the risk of a slightly increased bump up in A1C. For our diabetic patients and pre-diabetic patients, they emphatically say, hey, continue the statin. We optimize the lifestyle. Their glucose meds, everything else, but we don't abandon this medication, is what they say. And for the last section here, let's talk about the other side of the lipid panel, which are triglycerides. So, for years, if triglycerides were elevated, say 250, we reflexively reach for fibrates. The guidelines now are very clear for moderate hypertriglyceridemia, which is less than 500. Statins are your first-line therapy because our main goal is reducing atherosclerosis risk. And fibrates added to statins haven't shown to be beneficial from a cardiovascular risk perspective. The one major exception, though, is looking at omega-3s, right? So the reduced it trial showed that for our high-risk patients, those with ASCBD or diabetics with multiple risk factors who still had triglycerides between 150 and 500. Despite a statin, using four grams of pure EPA significantly cuts cardiovascular events. And so just watch for a slight bump though with atrial fibrillation with EPA. That's kind of the one thing we talk about in bleeding. That's a whole nother discussion. But now, if I fasting though, another side crosses 500 and especially 1,000, this changes our game, right? Our immediate priority shifts from preventing a heart attack. to preventing acute pancreatitis, right? So here we aggressively deploy very low-fat diets, fibrates, once again, never gem fibrazil to statin due to interactions. And we can also use high-dose omega-3s as well. So, we can add all those things. So, diet, we can talk about the fibrates, we can talk about omega-3s, all that stuff. And a quick word as well is on niacin here. It does come around and come up on the internet. The 2026 guidelines essentially say to avoid it, it does not provide incremental ACBD risk reduction when added to statins, and its adverse profile effect, including insulin resistance, flushing, and hepatotoxicity, makes it difficult to tolerate. Yeah, it's kind of the last line agent for severe hypertriglyceridemia. And as I mentioned in previous podcasts, if you have familial chelomicrinemia syndrome, there are different medications. That are fancy and we're not going to talk about necessarily. But usually that's when you're trying to treat them and it doesn't go down, like over a thousand and nothing's happening with your medications. But yeah. So that is it, though. That is our entire guidelines, essentially. Went through 100 plus pages for you. If you listen all the way through, I really, really appreciate that. That is some severe dedication. But hopefully, you have a better understanding of the guidelines. And once again. These guidelines aren't to make you a robot, say, I must treat like this. It's to understand them. Once you know the guidelines, you can then alter them and work them the best way you can for your patients. So, like, for me, the big thing is understanding these. So, I can learn how to use them with nuance, how to do my own thing, and understand where we're coming from, but then help you make those person-by-person decisions. That's what it's all about. And for all of my audio listeners, I really, really appreciate you listening week after week after week. It's been 170 plus weeks of me never miss an episode. And I'm just going to give you a heads up that I will be taking a summer sabbatical. Anyone who knows me personally knows there's a lot going on in my life. And so, it's just realistically not going to be able to produce pretty much any content for the next couple months. Um, fear not, I will be back, I promise, at some point. But I'm going to take a summer sabbatical just to kind of give me a break and get settled and do life. But, uh Yeah, I just wanted to mention that for anybody who's dedicated enough to listen to this on their podcast, Player of Choice, in their free time. First of all, I appreciate you. Like you can't even imagine. I appreciate you so, so much. But also, don't want to get worried about me. It's planned, it's going to be good. But I will see you later. I appreciate it. You following along, and we'll talk to you soon. Disclaimer, this podcast is for entertainment, education, and informational purposes only. The topics discussed should not solely be used to diagnose, treat, or prevent any condition. The information presented here was created with an evidence-based approach, but please keep in mind that science is always changing, and at the time of listening to this, there may be some new data that makes this information incomplete or inaccurate. Always seek the advice of your personal physician or qualified healthcare provider for questions regarding any medical condition.
