Mayo Clinic cardiologists Christopher V. DeSimone, M.D., Ph.D. , and Stephen Kopecky, M.D. review the drug inclisiran for cholesterol management, who may be a candidate, adherence and efficacy. This video was first published on Medscape Cardiology | theheart.org. Learn more about referring patients to Mayo Clinic.
Hello and welcome back to the Mayo Clinic Medscape video series. I'm Christopher DeSimone, electro physiologist here at Mayo Clinic today we'll be discussing lipid management and includes Aaron specifically. And I'm joined by my colleague Stephen Kopetsky, preventative cardiologist and professor of medicine at Mayo Clinic. Welcome doctor. Thank you. Doctor DeSimone. Well first of all, can you tell us about how inclusion works? Yes, inclusion is a very interesting drug, inhibits pCS canine but not through the way of the standard original drugs we have. This works actually by it's a small inhibitory RNA molecule drug. So actually inhibits the RNA from making the PCS Excellent. So different sort of mechanism of action right in results very similar now with the difference in mechanism of action. Is there any other effects we see like any effect on like a protein a Well there is just like we saw with the original PCSK nine inhibitors about 2025% reduction in el pa. Excellent. So we even added benefit from. Yes, very good. Now patients that are on this, does that mean they have to or get to stop their statins or is that something we keep them on? You know, we do keep them on. In fact the FDA recommended in addition to healthy diet the mediterranean diet like we recommend here and optimal statin therapy or maximum dollar raid statin therapy. Some of the guidelines actually say give that a minute to with it. So it's more of an additive effect because they have different mechanisms of action. Exactly. And because they have an additive effect that patients have better outcomes from this. Sure. If you get different mechanisms working together you can get a better outcome because as you get on a statin or the PCSK nine inhibitor drugs, you absorb more cholesterol in your gut. So that's where the vibe works. Excellent. So it's kind of like hitting it from two different angles. Just like blood pressure. You know, we give as a dilator a diuretic, a beta blocker. They all work together at lower doses. You can get away makes sense. One thing I think for our audience is how do you take this medicine? Is it a pill? Is it just like a statin medicine is an injectable like insulin? Yes, it's very interesting. It's injectable sub Q injection but the kind of the regiment is different. It's a baseline one month or I'm sorry, baseline three months. And then every six months you can check lipids at one month and you'll start to see a reduction, significant reduction by one month. So then every six months after that. So the adherence we hope will be much higher. Excellent. So basically when they do the injection, they don't have to inject it all the time. It's gonna be you know, once you get on that regimen every six months. Sounds much easier than doing something every day. Yes. Much easier and it will be done in the office or in the infusion center their infusion centers around the country, we have an infusion center here as you know at Mayo Clinic. So we'll know exactly when the patient got the drug. Did they get the right dose because we're doing it all ourselves. So will be very helpful to I think it'll help adherence because we're finding that the PCSK nine inhibitors that are sub q injected, self injected every two weeks and at the end of the year, only about 60% of patients are really still taking those. So we need to increase our adherence. You want to increase the adherence because you get so much of a benefit from these drugs but patients aren't taking them or no one wants to take shots so frequently then you won't have good adherence and you won't have good enough outcomes. Exactly. So the less shots the better the adherence. And when do you chew check the lip. It's so like when can patients expect the benefit I guess. Yeah. Well just like the statins which will start to see the optimal benefit in 4 to 6 weeks. The same with the with the enclosed current and then we can check it, you know, yearly after that, yearly after that. That's nice. Now what do the FDA or her practice guy then say yes this patient, you know, they're on statins, they're tolerating this. Well maybe they have some um additional work they could do with their diet. But where does you say this is the patient that would benefit from this? Maybe not just the patient that's not completely compliant but needs more like who would be your ideal patient? Well the FDA has said if you have a hetero sickos, familial hypercholesterolemia, hetero sickos, FH those that's an indication for the drug. Or if you have a S. C. V. D. You know, cerebral vascular coronary or peripheral disease and you're not a goal. And remember we haven't talked about this and but the new goals came out just a few weeks ago. So now if you have a S. C. B. D. The goal is 55 mg particular for the LDL which is a reduction from the 70 it was for the past four years. So that's the ideal patient to give it to. They can't get to go on a statin on a set of mine on a good diet, on a good healthy lifestyle. Then this would be someone to think of adding it in. Excellent. And one other question, you know, sometimes people have issues with statins as you well know and sometimes we try different doses or different types of statins but side effects from this drug. Yeah side effects don't seem to be a significant problem. There's always injection site, you know that's that's an issue. There is a little bit just like the PCSK nine inhibitors every two weeks they get a little nasal stuffiness or bronchitis or right rhinitis? The we're not really seeing any liver problems per se, no infection problems per se. But again, you know you study a drug in 70,000 patients. Then you release it to hundreds of thousands. And so we'll just have to monitor that closely but appears relatively safe. Yes. No it is quite excellent any issues if someone was to take this um around pregnancy things of that nature. Well it's the same guidelines we have for the other lipid lowering drugs we don't want to give during pregnancy. And so I tell patients that are potentially pregnant. Let's stop the drugs when you're thinking of getting pregnant and we can restart them the day after you stop breastfeeding. And now in terms of cost of this drug, how does someone go about? You know, obviously they would see their general practitioner, cardiologist and they want to be seen at a specialty clinic lipid clinic. But how do they go about getting this prescribed? And and what do patients have to go through? What are their expectations? Yeah. Good question. This is a little different in that it's not a drug. They go and pick up their pharmacy, take it home, put in the refrigerator. This is one where it's given at the center at the office. So it's not where the patient brings it in, it's there for them. And so the payment structure is a little different and they're still prior authorization as we're getting more and more with these drugs that we have to go through that that's more on our end of things. They do have centers that help us. You know, we have a prior authorization centers that help us. But every every drug is a little different. And every payer is a little different too. As you know. And it seems like that also helps the patient know, well, I'm gonna go pick this up rather than I'm storing it in the refrigerator or story in the cabinet and then helps with that compliance. Yeah, they just show up. Get the shot. They don't touch the drug, you know, the shots administered to them and they leave Excellent. Aside from the shot, anything that you tell patients not to take in terms of medicines, do we know of any drug drug interactions? Yeah, they really don't appear to be any drug drug interactions. That'll be something we'll have to be studied more obviously. But we're not we're not seeing that excellent. And then for a patient, what do you tell them what they could expect to benefit? So they're not a goal. And thank you so much for bringing that out that 70 is not the goal? The new goal is going to be 55 or the goal should be 55. But what does this give the patient? So they say take this medicine. What is like the reduction in mortality, cardiovascular events? Yeah. Well, you know, the it is interesting. We have great data for the statins and the PCSK nine inhibitors every two weeks. But remember the statins, it was years before we had evidence that we actually lowered mortality. The statins were approved the same now within glycerin. You know, those studies are ongoing. The Orion studies, those will be out in a few years and we all think they will show benefit because they're lowering it by a very similar mechanism, lowering LDL. So I think that will show benefit. Clearly, we just don't have the evidence just right there. So it's kind of like a don't wait for something really good to show up, be on it. And if there's low side effects, low risk and potentially really good benefit, that's something I would offer my patients as well. Yeah, I think it's going to be the convenience issue and the adherence issue that may really make the difference. It sounds much better to me rather than taking a drug every day. Well, in addition taking the drug every day, but shots frequently every six months. And you know, there's a model for that, it's called the osteoporosis drug year. So we have a lot of patients, the snowbirds fly up, they get their shot, they fly back down in the winter, they're happy with that Anything else important about the drug or things coming down the pipeline differences of this drug or stuff for patients to know. Or even our cardiologist primary care. Yeah. For these drugs, you know, we're starting to see the less frequency is starting to be the the name of the game. With this. We're starting to see drugs come along that actually lower lipoprotein a that's a whole different set of drugs. But these drugs that we're talking about today will lower 2025%. The new ones will probably lower 70 75%. So we have something to look forward to in the next few years, impressive. But we're always trying to get what's best for our patients as soon as we can. Exactly, exactly. And the one thing to remind patients, it's not just about, you know, the pill and not just about the shot. It's all about the lifestyle. We can't say, okay, this shot will replace healthy lifestyle, that doesn't happen chris we haven't developed that patients need to eat healthy and do the things that we tell them that it really can help their life. That's its own pill. Exactly, Exactly. Well, thank you steve for these very important insights and thank you for joining us on the heart dot org Medscape cardiology seminar
