180 - The Ultimate Guide to Statins: An In-Depth Drug Class Review

Welcome to Helix Talk, an educational podcast for healthcare students and providers covering real-life clinical pearls, professional pharmacy topics, and drug therapy discussions. This podcast is provided by pharmacists and faculty members at Roslyn Franklin University College of Pharmacy. This podcast contains general information for educational purposes only. This is not professional advice and should not be used in lieu of obtaining advice from a qualified healthcare provider. And now on to the show. Welcome to Helix Talk, episode 180. I'm your co-host, Dr. Kane. And I'm Dr. Patel. And the title of today's episode is the ultimate guide to statins and in-depth drug class review. So Dr. Patel, today we're talking about statins and everything a clinician needs to know about this really important drug class. This is really exciting because I teach it and so it's going to be an additional tool that I can give my students to review on the side. So thank you for doing this. Perfect. Well, why don't we start with just brain and generic names? And you know, when I teach really any pharmacotherapy topic, Dr. Patel, I always go through and I pronounce the brain and generic names because I think it's really important that as healthcare providers we call the drug the way it's supposed to be called, right? Right? Generically, all the generic entities and in statin. And then we have different brand names thereafter. Yep. So we have a torvostatin, brand name is lipitor, fluvostatin, brand name is less call, lovostatin, brand name is nevacore, and platythatin, brand name is live-alow. And then additionally, we have prevostatin, the brand name is prevacore. Vostatin, brand name is crustor, and cymbastatin, the brand name is zochor. And as we know, the statin, especially the cymbastatin, is available in combination with Zadia azidimid. Brand name is vitorin, if you happen to see it. So Dr. Patel, I think most people know, even patients, they know that this is their cholesterol medication, but they may not know exactly how it works. I think most pharmacy students know that these are HMG, CoA reductase inhibitors, which is sometimes the drug class, as opposed to calling them statins, although that's a mouthful. So most people know that there's an enzyme that is inhibited, but maybe don't know to connect the details of how that results and a beneficial effect for our patient. Right. And I like to, you know, just like I tell my patients, I tell to the students, too, there is two ways your body can be getting LDL. It's what your liver makes, which is like an intrinsic pathway, and the other one is what you eat, right? You're like your diet and things like that. So intrinsic pathway wise, it blocks these enzymes called HMG, CoA reductase in the liver. That particular enzyme is responsible for converting HMG, CoA into a volemig acid that then goes to production of cholesterol. By blocking it using the statins, we are basically stopping this cholesterol production, and that's why statins are called HMG, CoA reductase inhibitor. And we know that that's the primary mechanism, which is LDL reduction or bad cholesterol reduction by blocking your liver's ability to make LDL cholesterol. But we also know that there's some magic or pleiotropic effects that comes along with statins. What is a pleiotropic effect? A pleiotropic effect is basically something that is provided in addition to this main effect. Main effect is LDL reduction, but additionally we see that statins that it does help reduce risk of cardiovascular disease such as heart attack and stroke. And so there is this beautiful effect of statins for reducing inflammation, reducing or stabilizing that plaque, that goes even beyond what LDL reduction benefits that these statins provide. And we don't exactly know, I mean, we have hypotheses of how that happens, but that's where the word pleiotropic comes in of. Yeah, it does something else, we're just not exactly sure, but it's a good thing, whatever that thing is. We have many different statins as we covered earlier to kind of provide an overview like how exactly do they impact the LDL? As primarily as we explain via mechanism, that's the target, and then if there are any effects on other lipoproteins. Yeah, so it depends on the potency of the statin and the dose, but on the low end you're going to reduce LDL by about 20% and on the high end about 60%. So remember LDL is your bad cholesterol, so by reducing it more than half, that's actually our third picket goal in certain high risk patients. Yeah, and the other lipoproteins that we focus on is our high density lipoprotein, which is actually a good lipoprotein as well as triglystriids, which is that's a good one. The statins tend to have some effect, not that is great of an effect as they do on LDL, but they can help improve HDL by about 10%. And they could help lower the triglystriids anywhere between 10% to 30%. But again, if you're looking at your high intensity statins, they tend to provide the highest triglystriid reduction. And again, the main reason we're using these statins is for LDL reduction, so it's assuring or a good thing that these other lipid numbers are improving versus getting worse. Our main focus so is that LDL cholesterol for these statins, right? And then aside from statins, we do have other non-statin medications that could help us lower the LDL. Just kind of comparing where statins kind of stand among these non-statin therapies. So is that a myb or Zedia? We're looking at roughly a 15% to 20% LDL reduction, so that would be on the very low end of a statin. Vempidoagastid or Nexatol, this is one of those newer therapies out there. That also has roughly a 15% to 20% LDL reduction. Again, really not that impressive, it's there, but not as impressive. But the really impressive one is PCSK9 inhibitors. This is evalocumab or rapatha or alerocumab or praluent. And these have LDL reduction, similar to those high-dose hypotency statins of roughly 50% to 60% LDL, usually on top of what you get from the statin. This is quite a profound LDL reduction from that drug class, but you have to inject them in their expensive. Right, and technically they are approved for those with high acidity risk or LDL is not a goal, but we're going to see this in niche patient population, such as those with either heterozygous or homozygous familial hypocholestrolemia. When we do these episodes on Helix Talk, where we do a drug class review, one of the most interesting things for me is what is the difference between statin A and statin B, or inset A and inset B, or SSRIA versus SSRIB? So why do we take some time to talk about what are the differences between the statins as opposed to the similarities? Yeah, and it comes to specific knowledge required by pharmacists, this is what we are known for. So let's dive into the differences. So the first difference is LDL lower in in terms of how good of a job we do, and we kind of alluded to this earlier, but not all statins are created equal when it comes to how much they lower your LDL by. Yeah, so we kind of roughly have three categories per se, high intensity, which are categorized as those that lower LDL by 50% or more. We have the moderate intensity statins that lower the LDL somewhere between 30% to 50%, and then we have the low intensity that would lower the LDL by 30% or less. And I think, you know, we're not going to go through each one, but just to give a couple examples, the high-dose hypotency category, this is going to be a torvostatin 40 to 80 milligrams, or Rasuvostatin 20 to 40 milligrams once a day. Yeah, and then if you look at the moderate intensity statin, again, we have many examples, but agents like some of statin 20 to 40 milligrams or Rasuvostatin 40 to 80 milligrams fall into this range. And then that low intensity statin category is kind of interesting because we almost never start patients in this category, but patients may end up here if they don't tolerate higher doses. So, a couple examples would be Sympastatin 10 milligrams, Pravastatin 10 or 20 milligrams. So, these are really low intensity low-dose statins that we don't typically use unless a patient is intolerant to a higher dose regimen. Right. And if you really need to move the needle, meaning make an impactful change in the LDL, rather than changing the intensity, for example, going from 10 milligrams of Pravastatin to 40 milligrams of Pravastatin, it's actually just better to change the agent altogether. So, that you are looking at additional LDL reduction. And numerically, double in the dose gives you roughly a six-ish percentage point difference in your LDL. So, even if you quadrupled your dose, you're looking at 12 percentage points lower for your LDL versus if you go to that high dose statin, it could be a much bigger magnitude of benefit. Right. And then they also differ in terms of their half-life, and then that's why we tell patients to take them at a specific time. So, the longer half-life statins tend to be those high-potency LDL reducing statins. And then most of these statins have longer half-life, and we are ranging it between 12 hours to 19 hours, even some active metabolites of a term of statin leading up to 30 hours of half-life. But most of the other statins that aren't as long-acting, they're going to have half-lives that are measured and just single-digit number of hours, so like one to three hours. And because of that, the recommendation is when you're taking these shorter half-life statins, so that's not a Taurus statin, a Rousseau statin, or a Patata statin. But all of the other ones, the recommendation is to take these at night, because most of your cholesterol production occurs at night, and you're trying to maximize the peak effect of the drug with the peak cholesterol production. Right, so you could get away by telling your patients if they're getting a Taurus statin, a Rousseau statin, or a Patata statin, that they can take it at any time of the day, rather than taking it at night, but all the other ones, they'll have to take it at night. Right, there comes a little bit of patient-specific or shared decision making point two. If your patient tells you, hey, you know, I fall asleep and miss my night medications like five times out of the seven nights, perhaps it's a good idea to change them to a long-acting statins if they qualify for their high intensity, and then that way they can take it any time of the day. And just to put a number to it, there's been at least two crossover trials where they've compared taking it at night versus taking it during the day, mostly with some of the statin, and the difference is about five to ten percentage points of LDL reduction. So it's enough that you would notice it, but it's not so much that it means that the statin has no effect at all if you take it in the morning. But it agreed, like for the most part, if compliance at night is really that big of a problem, it's probably just better to use a long-acting statin. They're very inexpensive now. We're two, three decades ago, they weren't. So, cost is really not as big of a factor anymore. Right, because they are all not available as generics, so that's good. The other way they differ is their metabolism, so what pathway they take in order to go through the metabolism. We all know about the tip three for metabolism, so that's our agent such as a torvostatin. It's going to go through cymbastatin, as well as lovostatin. There are other statins such as flugostatin, pitabasatin, rosuvostatin. They go through metabolism, but they are not the three, eight, four. The one that I like to point out that's a little bit different is our pravostatin. It doesn't go through the sip mechanism, it goes through glucuronidation. So, if you have patients on sip three, eight, four substrates or inducing or, you know, inhibiting medications, medication like pravostatin can come in handy because then you're not looking for those drug interactions. I think that's important enough that we just highlight one more time. So, pravostatin generally has the fewest drug interactions. Sympostatin, a torvostatin, and lovostatin tend to have more or the most drug interactions. Then all the other statins are kind of in the middle. They do go through sip enzyme systems, but they're not heavily reliant on three, eight, four. So, you can see interactions, but maybe not as much as those top three, but you can wear lovostatin, sympostatin, and a torvostatin. So, you know, we take these to lower cholesterol, right, Dr. Fatel, but we also take them really for the bigger benefit of not having heart attacks and not having strokes, right? So, it's great if your LDL is better, but we've seen drugs historically that make your lipid panel better, but don't change your risk of heart disease. So, do we, hopefully, we see a benefit in terms of heart disease with these, right? We do. You would say, again, this depends on the intensity of the statin as well, but if you're looking at our higher intensity statin, we're looking at about 35 to 45% reduction, our lower intensity or lower potency statins, we're looking at 15 to 25%. So, on average, about 30% reduction, we see in these events such as heart attack and stroke. So, then if you think about it, you know, for the audience, it's familiar with the ACVD 10-year risk calculation. That's your risk of having effectively a heart attack or a stroke in the next 10 years. If your percent is 10%, that means that if you take a statin, instead of being at 10% risk, you'll go down to 7%, a 30% reduction. So, you still have a risk. It's lower, and that 30% is roughly the clinical benefit that we observe. Yeah, and if we are talking about patients who are using statins for something called primary prevention, meaning they haven't had an event yet, they haven't had a heart attack or a stroke, versus those people who are now taking it to prevent a secondary heart attack or secondary stroke, is there a difference? Generally, yeah. So, when we think about the number needed to treat, which is related to how big of a benefit you have, but also the incidence rate of that, people who have had heart attacks and strokes are more likely to have heart attacks or strokes in the future compared to someone who's never had it. Generally speaking, the number needed to treat or the number of patients that are going to benefit from statin therapy is going to be better or higher if you are focused on a secondary prevention population versus a primary prevention population, but both populations definitely do benefit from statin therapy. And earlier, we compared the statins with the non-statin agents for their all the other reduction. How do statins compare with some of these non-statins when it comes to reducing this ascivity of us? So, it's actually not even competitive, Dr. Patel. So, statins are way, way better when it comes to reducing your risk of heart attack and stroke. Now, with that said, all of the other non-statin therapies generally have been studied with background therapy of statins, so that means that their benefit is on top of statin therapy, so you have to take that into account. But, remember, statins are roughly at 30% relative risk reduction. Is that a mild or a zedium? 6%. That's pretty low in terms of the benefit, and that was really only seen in the improved trial, which was a very specific high risk patient population. Benpidoc acids or nexatol is at 13%, which is better, but still not 30%. And then our PCS-K9 inhibitors, remember, these are the ones like Evolokimab and Alarokimab that had this really impressive LDL reduction. Despite that, their relative risk reduction is only about 15%. So, still there, a little bit better than Benpidoc acid, which is a little bit better than Zedimib, but still not at 30%. So, statins are really the king in terms of having the most bang for your buck in terms of ascivity risk reduction. And this is great coverage of statins effect, right, in terms of LDL reduction versus their impact on this cardiovascular morbidity and mortality. But now, if we can boil it down and talk about what patients are made for stands, who should get statins and to what intensity statins they should get it. So, we do have this link to our show note, but there is a 2018 ACCHA blood cholesterol guidelines. According to the guidelines, there are four different categories of patients that are considered our statin groups or statin benefiting patients. So, for primary prevention, remember, these are patients who have never had a heart attack, stroke, peripheral arterial disease, the symptomatic. Those patients might get a statin if their LDL is really high, so 190 or higher, which generally is in the category of this familial hypercholesterolemia. It's a genetic predisposition versus a bad diet, for example. So, they definitely qualify. So, these patients are going to get actually a high intensity statin. Then we have patients with diabetes who are between 40 to 75 years of age, and we're looking at their LDL level between 70 to 189. And the recommendation is to at least start with moderate intensity, and then if they have one or more ASCVD risk factors, hypertension, obesity, you know, all that stuff, then they could go up to high intensity statin. And then our third primary prevention group are patients that don't have diabetes, don't have a really high LDL, but they do have an elevated ASCVD risk, that 10-year risk. And most of the data is those that have a risk of 7.5% or higher, so in the next 10 years, the risk of 7.5% or higher. But the guidelines do say that you might consider it kind of a gray area for the 5 to 7.5% patients. It's more shared decision making, looking at other risk factors, things like that. And then the category or the potency of statin that's recommended for this subgroup is moderate intensity statin. And so we covered three benefit groups so far, Dr. Kane. The last one is obviously patients who had an event before, right? So these are our secondary prevention patients. They had a stroke or a heart attack or maybe they got a four vessel cabbage done or something like that. These patients are going to be indicated for statins, and the recommendation is to go with high intensity statin. So Dr. Kane, this was a good review of, you know, who are these four categories of statin benefiting patients and what intensity statins we should put them on. One thing I wanted to provide a disclaimer of is for most other pharmacotherapy, talking about blood pressure therapy, blood sugar therapy, you're going to see an initial dose or kind of have this mantra call start low ghost though. When it comes to these statins and these benefiting groups, you want to go with the intensity of statin that is recommended. So if it says high intensity, we go with the high intensity. If they don't tolerate the high intensity, maybe we can, you know, move it down to moderate or add other non-statin therapy as needed. But we don't do the start low ghost low approach with statins. So we kind of alluded to this already, Dr. Patel, but there are drug interaction considerations when it comes to statins. And the first category is the one where we're going to talk about, which is Cetacrom P450, mostly in inhibition. So remember it's a Taurus statin, Cemestatin and Lovestatin that heavily rely on 384. So if you have a drug that inhibits the 384 pathway, those statin drug levels in the blood are going to go up, and you're more likely to see a side effect from too much statin drug concentration. Yeah. Fucanos all comes to mind as one example. If you look up the label for Cemestatin, you would see plenty of drug interaction because they did a study on it. And now you have a limitation of like, okay, if you're using amlota peen with it, you can't go more than 20 milligram of Cemestatin. It's again agent specific, but yes, these Cetacrom P450 are real, especially with a Taurus, Cemestatin and Lovestatin. And then the other one is Jim Fibrezil, and this is actually pretty relevant because it's not that uncommon that patients have mixed dysipidemia where they have high triglycerides and they might want to vibrate, and a high LDL and they might want to statin. So what's going on with this one? The bottom line I tell students to do is do not use John Fibrezil. It's a type of of vibrate or phenophabric acid category of medication. It works by lowering triglycerides and so with patients who are having, we call it mixed dysipidemia or dysipidemia where their triglycerides are high and their LDL is high, we need a therapy that can help lower the triglycerides. The Jim Fibrezil is going to actually interfere with statin glucuronidation, so during that phase two metabolism. So again, the bottom line is, you know, try not to use it. If you look at certain statin label, in their label, use of Jim Fibrezil is actually a contraindication. And some statins don't have it. Plus Jim Fibrezil, you know, you're asking patients to take it two or three times a day. Why add that pill burden? We do have another phenophabric acid or phenophibrate medications out there. They do have interaction with statins, but they are much safer than Jim Fibrezil when it comes to combining with statins. Which should say that, again, the risk here is that statin drug levels can get too high. You get muscle pain, which we'll talk about soon. It's toxicity of the statin that we're worried about. In the same vein, grapefruit juice. And I think anyone who's ever worked in a pharmacy probably remembers all that do not drink grapefruit juice stickers that come along with that prescription bottle. And interestingly, but probably not surprisingly, that the impact of grapefruit juice as an interaction depends on which statin you're looking at. Yeah. That's really interesting. And I have students telling me sometimes, "Oh, I read somewhere like you shouldn't do more than 1.2 liter." And I'm like, "Who drinks 1.2 liter?" A lot alone, someone like me who can tolerate grapefruit juice or grapefruit. But let's say one example, right? Look at SimuSantin. It says, you know, 200 milliliters, one's daily code cause almost four times increase in A to C area on the other of the curve or C max, which is the maximum concentration of the drug. And that would be basically like a glass of grapefruit juice. So it's not like 1.2 liters. We'll get to the 1.2 liters in a second. But that's like a normal amount of grapefruit juice that if you consume it, for a fold-in crease, that's like you took four SimuSantin tablets instead of one. That's actually a really big deal, right? And this could easily lead to those myopathic style side effects. So then a torvastatin does have this interaction, but isn't as notable in terms of the magnitude of effect. So there was a study that looked at a similar volume, 240 milliliters of grapefruit juice. And it basically increased torvastatin drug levels a little bit, but not that much. But then there was another study that looked at 200 milliliters of double strength, which I didn't even know was a thing, but double strength, grapefruit juice, three times a day. So a dramatically higher dose and that tripled your a torvastatin drug level. So this is where that 1.2 liters comes in is 200 ml times 2, because it's double strength times 3, because it's three times a day. That's where the 1.2 liters comes in, which is actually in the package insert for a torvastatin. And as you said, like I can't even stomach the thought of drinking more than a liter of grapefruit juice. I don't know where that comes from. That's a big amount per day. And then if you look at Travis set and there is no drug interaction at all, right. So again, this grapefruit interaction is definitely specific to certain standards. Yeah. And so really, you know, if someone wants to have a glass of grapefruit juice on a torvastatin, probably not a big deal. But if they consume quite a bit of it, that probably could be a big deal with the torvastatin and definitely with semestatin. With semestatin, again, you don't have to have that much to really have a profound increase in your drug level. Well, aside from these drug interactions, we do definitely educate patients on satin side effect. And there are pretty prevalent side effects out there, especially the myalgia. But we do have some rare side effects discussed as well. And there is a lot of focus on side effect and how to manage satins based on these side effects in the guideline itself as well. So definitely check out the show no link. What's interesting. So we'll start with the most common one, which is myalgia's. And this is where the patients having muscle pain. But if you check their blood levels of creating phosphokinase or CpK or Ck, it's normal. So you don't have biochemical evidence of muscle damage, but they're having muscle pain that can be pretty limiting in terms of being able to walk without pain and things like that. And if you were to ask patients to describe what that muscle pain is like, they're going to say, oh, it's happening in both of my thighs. So we're talking about bilateral presentation in very proximal muscles, so bigger muscle systems. And it could occur anywhere from weeks to months after statin therapy starting. And if it's really coming from statin and the way to find out this is if you stop the statin and give them 10 to 14 days without statins, if they say yes, my muscle pain might obey, then we can confirm that it really came from statin. And this is really the only clearly common adverse effect of our statins. When I say clearly common, I mean the incidence rate is up to 20% in real life patients, maybe as low as 5%, which is probably more accurate. And interestingly, in randomized control trials, it's a little bit lower 1 to 5%. Probably in a self-selecting group of patients that are a little bit healthier. So this is definitely a side effect that occurs, and we have a pretty good sense that the incidence rate is not less than 1% let's say. But the ones that are fairly rare with statin therapy are then myopathy. And I have to do, I do have to teach students the difference between what is myopathy. So myopathy is when you have that myolja muscle pain, but then you would also see a lab abnormality. So you'll see an elevated CPK levels. This is again, really rare. You would see with statins warning of rabidomyelosis. Again, this is a severe type of muscle breakdown that manifests not only with muscle pain, but also very elevated CPK. We're talking 10 times the upper limit of normal. And when the muscle breakdown happens, our body produces myoglobin, which is technically toxic to the kidneys. So patients may also present with acute renal failure. Then there's some side effects that have kind of come out more in observational studies. And I would say we're not exactly sure if statins definitely cause it or if it's more association versus causation. But one that has come up more recently is an increased risk of the development of diabetes. And the risk kind of depends on what the patients and transit risk of diabetes is. So overweight already has an elevated fasting glucose value, something like that. But the risk is roughly 9% increased risk over about four years. So an odds ratio of 1.09, which isn't nothing, but also not that dramatic either. And if you look at the studies that showed this, probably is studies that use high intensity statins or higher doses of statins. And when it comes to, you know, patients with diabetes complaining that, oh, this may disrupt my blood sugar. I tell them it's better to not have a stroke or a heart attack when you have diabetes, but your risk is really high. Then have a little bit of elevation in blood sugar that we can manage with their anti hyperguysine next. Absolutely. So in my mind, this is a non-issue because the benefit of the statin clearly outweighs the risk of developing diabetes. Absolutely. The other one is increase in LFTs. I almost think that the manufacturers should take that away from the labeling because we don't get to see it. It's very rare and infrequent. In fact, patients who have the fatty liver disease, they would inherently because there is scarring on the liver tissues and stuff and injury to the hepatocyte, they would have increased LFTs. But hey, the treatment for this patient is actually statin therapy because fatty liver disease, it's the fat deposit, we need to bring it down. Right? So you could use statins in patients who have liver injury, as long as it's not acute liver injury. However, the pure association of how statins cause liver injury is really rare. And then our last one, which is probably the least proven connection to statins is memory or cognitive impairment. This is really rare. We've seen some case reports kind of focusing on this, but there's at least been three RCTs, randomized control trials that have said that this is not a thing. So patients may ask about this. In my opinion, the dig is not clear enough. This is definitely a side effect associated with statins. Yeah, and if you look at some Alzheimer's studies that came out recently, it says it actually helps to reduce amyloid plaques. Right? So there is a beneficial effect seen in some of the childs. Nonetheless, if you have an older patient where you're collaboratively be talking with the providers and patients and their caregivers and really the statins doing it, you could stop the statins. Obviously, risk-courses benefit should be discussed. And the memory impairment actually is reversible. So in terms of the statins associated muscle symptoms, and this is actually abbreviated in the guidelines as SAMS statins associated muscle symptoms, this is the main side effect, right? So are there risk factors? And what do we do if a patient does experience SAMS? Yeah, so they have listed a pretty good number of risk factors. One is older patients. And how are they defined? 75 and older is how they are defined. Those patients tend to be at a higher risk. Those who have lower body weight, those patients who exercise, I'm talking weight lifting, not just like mild or moderate aerobics. So heavy exercising patients. And then obviously patients who have potential for drug interactions. Right? So we talked about some of the drugs earlier. But even those who are using non-statin therapies for their mixed disobedientia, these patients are going to be at a higher risk. And so this is a huge intervention point for the pharmacist to have in order to mitigate some of these drug interactions. Right? Greyfruit was one example. That's an easy fix, easier fix. Then actual drug interaction. But yeah, these are our risk factors for satin-associated muscle symptoms. So then if you think your patient is having that in collaboration with the prescriber, the steps would be to stop the statin and see if it gets better. Yeah. And if it doesn't get better, it's not the statin. Yeah. We know that it will improve with this continuation. But then if it does improve, what are our steps there? Are they never going to get a statin ever again? Probably not. But what do we do? Yeah. My motto is a little bit or something is better than nothing. So we should definitely try to reduce the dose of the same satin. So let's say the myalgia happened from simostatin 40 milligram. We should try and see if they will tolerate simostatin 20 milligrams instead or even 10 milligrams. So that's we are jumping the satin intensity category here. Or you could choose a different statin altogether. Right? So for example, if the myalgia is really coming from the drug-drug interaction, we want to avoid that sip interaction. Perhaps preface statin would be a better choice for this patient. So changing that could also help. And I think what's promising is numerically, a majority of patients will be able to tolerate a statin, typically at a lower dose and alternative statin, as opposed to never being on a statin in the future. So it's worth it to try because the majority of patients will be able to get on some statin therapy as opposed to never being able to qualify for statin in the future. Right. And I do see this in a patient's chart on and off that they would be labeled as, you know, they're intolerant to simostatin. But then the provider, when trying to talk to the patient about risk reduction, they will just say, oh, well, you're intolerant to statins. Don't label your patient if they've just failed one statin. Try other statins and see if they would work. So I know historically, some providers would give something like coq 10 or ubiquinone because there was a thought that deficiencies of those two vitamins or supplements might be related to the myalgias that happen with statins. Is that a thing? Yeah. So, you know, chemically speaking and methodologically speaking mechanism wise, that makes sense. Why would you want to replenish coq 10 because you're exhausting this ubiquinone molecule in the metabolism of the statins. But when you look at clinical trials, they did not improve the myalgia. So technically, there is no role in statin therapy. However, if a patient believes it's a sugar pill effect, right? If a patient believes that they are able to take their simostatin or a turvistatin because they are taking their coq 10, let them do it because I rather them take the simostatin or turvistatin, then not take it at all. So then in terms of when we start our statin therapy, so we already talked about the probably statin labeling should be updated about the LFT risk and things like that. What types of labs do we need to get at baseline? And then what kinds of labs do we get on a recurrent basis? Yeah, I think with saying that about LFTs, I would still be more comfortable if I don't know the patient seeing them for the first time that I evaluate LFTs at baseline before starting. Obviously, you would want to know where their lipids are so you can compare when they come back for monitoring as to how their levels are improving or not. So I would check their baseline lipid panel and I would check their baseline liver panel, which would give you your LFTs. So then in terms of when you get that repeat lipid panel, you want to give enough time that their cholesterol numbers are impacted and kind of at a new study state. So how long does that take? So the earliest you can do it is a month, so four weeks. You could do it up to 12 weeks. So four to 12 weeks. I'll tell you in reality in my clinic, we do it three months if we do it to check the efficacy of the statin. And what's interesting is, you know, this isn't just your opinion of LFTs at baseline, repeat lipid panel and lipid panel at baseline. Your guidelines literally weigh in on what do you get at baseline and what do you get on a routine basis. And they are very clear in terms of other stuff that you get after you've initiated therapy. You do not routinely need to get creatine phosphokinase or creatine kinase or CPCK and you do not need to get your LFT, your liver function test routinely done. And this is really a departure from probably 20 years ago when these were very commonly routinely done, the guidelines say do not do this. Yeah, because we know satins don't cause the LFT elevation, not not routinely again. And the injury to the muscle where you would see an elevation in CK or CPCK is also very rare. So we don't need to waste lab money. However, if your patient does present with that muscle pain or weakness or have jaundice-like symptoms where you think there is some liver issue going on, then you may want to use your clinical judgment and take it. Not routinely, but only in certain patients. So, Dr. what do we round out today's drug-class review episode with some clinical pearls or counseling points that are notable that don't fit cleanly into a given category. So for me, one of those is statins are tragic. So you can't take a statin if you want to get pregnant or you're pregnant, you have to stop the statin. The other category then we think about after pregnancy is what about breastfeeding, right? Well, when the baby is getting nutrition from mom, cholesterol is an important component of breastfeeding. So you don't want to limit the amount of cholesterol that that's being passed. However, there is, clinically speaking, there is not much data how much drug enters the breast milk itself. Of the data we have, it seems like it's not that much. So most of the don't breastfeed recommendation is more about nutrition to the baby versus drug exposure to the baby, right? And then the other category that comes up quite a bit is, you know, the guidelines are pretty specific about 40 to 75 years old and that's the age category for qualifying for a statin unless you have crazy high LDL. But what about those really old patients? So people who are more than 75 years of age, do they get a statin or not? And I see this all the time, the older individuals are on statins, but why, why do the guidelines draw that line at 75 years old? This is where the shared decision making comes in, right? And this is, quote, unquote, adding statin is reasonable for both primary and secondary prevention for patients who are 75 years of age or above. This is going to be that discussion between patient and the provider, whether you continue or not. And this is coming from some of the gaps we've seen in the right and rights control trials in patients who are 75 years of older. So again, your benefit from statins doesn't come next year or two years later, it's usually very cumulative. So when you're looking at benefit of statin, it's about 30% over 10 years. At 75 years of age, are you really trying to increase the person's age by 10 more years, right? So again, looking at the lifespan, looking at the prognosis with multiple different comorbidities that these patients may have, it's really a patient provider decision whether they continue or not. And just to put some context to that, if you had an 80 year old who is still running marathons and, you know, very active, very few comorbidities, but they have a statin indication, they're probably going to live till they're 90 and it makes sense to give them a statin. But if you have an 80 year old whose bed bound has had multiple strokes that has terrible quality of life, maybe it doesn't make sense to give them a statin, both because they probably won't live long enough to derive the benefit, but they are potentially going to have some of the side effects and drug interactions associated with that statin therapy. Yeah, so you kind of balance out the benefit and the risk for short. And then last but not the least, just like we say about other chronic disease medications, statins are chronic therapy. So yes, you may see a lab reduction in LDL within within your four or 12 week of monitoring, but that other benefits of statins where we are seeing reduction in mortality and morbidity of cardiovascular disease, that doesn't come in a year, doesn't come in months, it comes over years. And so when you want statins, you're going to be on satins for a long period of time. And you know, this comes up frequently for happy students in the ICU as an example where they feel like, oh, you have to give them their statin back otherwise we're going to have a heart attack. It's not true. So you can acutely stop a statin for a drug interaction or an acute illness or whatever the reason is, obviously we want our patients to take it as much as possible over a long period of time. But if they miss a week because they don't feel well or they miss a week because they need to take packs of it or whatever, that's not going to hurt the patient because this is a long term chronic therapy that the benefit is derived over years, not days or months. Right, because these plaques develop over years. So the benefits also come over years. So kind of rounding out today's episode with a couple key points. One is that statins primarily reduce your LDL cholesterol and it's somewhere between 20 and 60% depending on the statin selected and the dose picked. And they have a modest, but favorable effect on HL cholesterol and triglycerides. Clinically, we use these because they help your LDL, but mainly we use them because they reduce the risk of heart attacks and strokes by about 30%. And again, there's a range in terms of the benefit based on the potency of the statin. And there are four main groups of patients who are indicated for statins. These patients are those with LDL of 190 or above those with diabetes and age of 40 to 75 years of age, but the LDL is between 70 to 180. Those patients who do not have diabetes or AACBD, but an elevated 10-year AACBD risk score of 7.5% or above or even with decision making between 5 and 7.5%. And then those patients who have had an AACBD event. So this is our secondary prevention patients. And then from a drug interaction standpoint, a Torvastatin, Lovastatin and Sympastatin heavily rely on CP3A4. And for that reason, they tend to be more prone to drug interactions versus something like Pravastatin that goes through phase 2 metabolism. And again, this point we can't emphasize enough as pharmacists. We are involved in medication monitoring as well. When you are starting a patient on statin phase line, you would want to get their lipid panel as well as LFDs. But after 4 to 12 weeks, we can check the efficacy of statins and we can repeat a lipid panel. We do not have to repeat the lipid, a liver function test or CPK routinely. You could do it in patients who have accompanying symptoms such as muscle pain or jaundice like symptoms. So that wraps up today's episode quite nicely. So a statin drug review, we do have a reference in our show notes and that's at helixtalk.com. Again, this is episode 180. We're also on Apple Podcasts and things like that. So we love the Fist Our Review and however you're listening to us today. And we also have a mailing list. So if you go to our website helixtalk.com, you can subscribe and you'll get an email whenever new episodes come out. So with that, I'm Dr. King. And I'm Dr. Patel. And as always, study hard. If you enjoyed the show, please help us climb the iTunes rankings for medical podcasts by giving us a 5 star review in the iTunes store. Search for helixtalk and place your review there. To suggest an episode or contact us, we're online at helixtalk.com. Thank you for listening to this episode of helixtalk. This is an educational production, copyright, Rosalind Franklin University of Medicine and Science.