Hey, everyone, it's Chris Romero, we're going to give everybody a few minutes to log on here. And before we make our introductions, give you a few minutes to get set up. Okay, well, while we're letting everybody log on, I'm going to go through a few housekeeping items. Again, this is Chris Romeo, I'm the Executive Vice President of the Ventures team here at MedAxi. Today's presentation is Targeting Cardiac Inflammation as an Approach to CV Risk Reduction. This is sponsored by AGIFA Pharma. And before we get started, I want to go through a couple of housekeeping items. Down at the bottom, you've got a couple of options. One is a chat feature. The chat feature, there is actually a presentation link to today's presentation. You can download this presentation, share it with your colleagues, or review it at a later point in time. The other button that you should be looking at is the Q&A button. The Q&A button is where you'll enter your questions. We're going to hold off on posing those questions to Dr. Canto so that we can get through the slides. And then at the end of the presentation, we'll be answering as many questions as we can today. So with that, let me introduce you to Dr. Canto. Dr. Canto is a cardiologist and cardiovascular epidemiologist at the Watson Clinic in Lakeland, Florida. And he is the Director of the Center for Cardiovascular Prevention, Research, and Education, and he's the Director of the Chest Pain Center at Lakeland Regional Health. He was previously a faculty member of the Division of Cardiology at UAB, where he was a tenured professor. While at UAB, he received numerous teaching awards, such as the Best Clinical Teacher in the Department of Medicine, and also the Best Clinical Teacher in the Cardiovascular Division. He has published well over 100 peer-reviewed articles and abstracts, and is a medical reviewer for numerous medical and cardiology journals. Dr. Canto is also the cardiologist for the Detroit Tigers in Lakeland, Florida. With that, let me turn it over to Dr. Canto, and we'll be back to you at the end of the presentation for questions. Dr. Canto, all yours. Thank you, Chris, and good afternoon. Our topic today is targeting cardiac inflammation and CV risk reduction. I reflect on my 31-year career as a cardiologist, and my lifelong passion and dream is to stamp out cardiovascular disease. This means cardiovascular research to find a cure. This means cardiovascular education to healthcare providers and cardiovascular education to our patients. This means aggressive, intensive lifestyle modification and aggressive, intensive, comprehensive medical management. Every risk factor matters. The key phrase you will hear today is cardiovascular prevention and residual cardiovascular risk on max tolerated statin. I will make the argument in the next 40 minutes that inflammation is an important factor that possibly may tie all the cardiovascular risk factors together into one, and perhaps give you a better appreciation of addressing inflammation when you see your CVD patients on a daily basis. Next slide. Shown on this are my disclosures in both research and as a speaker. I'm not paid to give this presentation by MedAxiom, Agefa, or any other company. Let's start out with a case, 61-year-old male, a number of risk factors listed there, history of stent to the LAD four years ago, but you're seeing them because they had a recent heart attack with stent and on fairly aggressive optimal medical therapy and is obese on exam, otherwise unremarkable, and the EKG confirms the old anterior MI. We'll go back to this case and review it in more detail. Next slide. So LADOCO was approved by the FDA as the first anti-inflammatory drug for cardiovascular disease, June 20th, 2023. LADOCO is low dose, colchicine 0.5 milligrams. In the U.S., we're familiar with colchicine as 0.6 milligram dosing for the treatment of acute gout and also acute pericarditis. Agefa, which is a European company, studied the 0.5 milligram dose for CBD risk reduction and thought, maybe we can bring this drug to the U.S. at the new dose. And they applied to the FDA and were granted acceptance June 20th, 2023. And you can see LADOCO is indicated to reduce the risk of myocardial infarction, stroke, coronary revast, and cardiovascular death in patients with established ASCVD or with multiple risk factors. The drug has hard cardiovascular benefits. Colchicine has been around since 1500 BC to treat joint swelling. And in 1961 was approved for use in the treatment of acute gout, then later familial Mediterranean fever and more recently acute pericarditis. The mechanism of action to prevent cardiovascular events is largely not understood, but we do know that colchicine reduces activation and migration of neutrophils, decreases the production of pro-inflammatory cytokines and other inflammatory mediators, and has an anti-inflammatory effect, which may improve cardiovascular health and reduce plaque instability and lower your risk for thrombotic events. Shown is a publication. I was the lead author in JAMA and American Journal of Cardiology, where we examined individual CHD risk factors at the time of initial MI using data from the National Registry of Myocardial Infarction over 1994 to 2006. This registry has enrolled 2.5 million Americans with confirmed heart attack, and we confined this analysis to those with initial MI. The first point I'd like to make is that majority, that is 86% of Americans who present with their initial heart attack had the presence of at least one confirmed CHD risk factor, debunking the myth that half of patients with confirmed heart attack do not have the presence of a risk factor. You can see that hypertension is the most common risk factor at 52.3%, largely mirroring the general population of Americans who have 60 to 70 million Americans with hypertension. This is then followed by smoking. In our analysis, smoking was the number one risk factor for premature heart attacks in men and the number one risk factor for premature heart attacks in women, followed by high cholesterol, family history for premature heart disease, and then diabetes. Eventually in the 14.4% of subjects with no risk factors, age eventually became the risk factor, and they were associated with the highest risk for death in our analysis. In this registry, we did not have the ability to track inflammation. Shown on the next slide, arguably genetics may explain over 90% of all heart attacks, and to date, 40 to 60 candidate genes have been identified in the causal pathway for The future might be you get a buccal swab and a probability of how you might fare with regard to suffering with a heart attack and heart disease in the future, but use have showed that nine modifiable risk factors explain 90% of the heart attack risks. We know about exercise and aerobic activity, but don't forget about strength, stretching, and stability and mobility. Weight management, you never want fat around your gut and the organs you're trying to protect. The importance of nutrition with a diet high in fruit and vegetables, lean protein, minimizing saturated fats and trans fats, the importance of two servings of fish per week, blood sugar, blood pressure, smoking, and also the importance of sleep and stress and then cholesterol. But one risk factor may actually tie all other risk factors and narrow the gap of the additional 10% of unexplained risk factors, and in my opinion, this risk factor is cardiac inflammation. Next slide. We know that multiple risk factors cause systemic inflammation. So I came up with this slide looking at the traditional risk factors, but also add stress, poor sleep, poor nutrition, which itself may cause systemic inflammation. Although the arrows point outward, they certainly can point inward and inflammation with CHD risk factors listed here may in fact cause atherosclerosis. Next, perhaps we're just dealing with one disease process with inflammation of arterial vascular wall, the common thread. Obesity is the new public enemy number one, and according to the CDC, 42% of Americans are obese and 73% of all subjects are overweight or obese. And this is followed by diabetes, 37 million Americans and a staggering 96 million with prediabetes and insulin resistance. Next slide. Aggressive risk factor modification with lifestyle changes and aggressive intensive medical therapy is really indicated and arguably lower, maybe better, and no threshold is identified with regard to hypertension, cholesterol, diabetes, and then certainly with weight management. Next slide. In 2004, when I came here to the Watson Clinic, in the front pages of Time Magazine, they highlight the new secret killer linking inflammation with heart attacks, cancer, Alzheimer's, and other diseases. You see, C-reactive protein is the marker of choice for measuring inflammation in the body. It predicts incident risk for MI stroke, PAD, sudden cardiac death in primary prevention in patients with no established cardiovascular disease, and also secondary prevention in patients with acute or stable coronary syndromes. C-reactive protein is the protein made in the liver. The marker itself is not felt to be directly involved in the causal pathway of disease. And you have what's called high sensitivity C-reactive protein, which is a test more sensitive than the standard C-reactive protein and detects smaller increases in C-reactive protein than a standard test can. Next slide. We're going to review five landmark studies which make me arrive at this conclusion that inflammation is vital to understand. Four will come from the New England Journal of Medicine. If you want to read one landmark studies, read the New England Journal. That's very important. And one's from the Lancet. And the first three are from Dr. Paul Ridker from Harvard. He's taught all of us in cardiovascular prevention and cardiology so much about the important role of inflammation. And some of these slides were borrowed in part from his work. So shown here is the JUPITER trial. They studied subjects with no compelling indication to be on a statin who had apparently normal LDL levels, but an elevated CRP rather than two in primary prevention. They randomized subjects to a placebo versus resuvastatin shown in the Kaplan-Meier curve in the gray in the middle of your slide. The study was projected to be four years and was stopped after only 1.9 years because of a 44% reduction in the primary endpoint of MI, stroke, revast, and death. Very interestingly, if you look at, for example, myocardial infarction alone, 63% relative risk reduction, highly statistically significant, 48% reduction in stroke, highly statistically significant in and of itself, coronary revast, 46%, highly statistically significant, and even all-cause mortality was reduced a whopping 20%. This was seen irrespective of family history, body weight, presence or absence of metabolic syndrome, Framingham risk, and really in all participants. Next, CANTOS trial, no relationship to my last name, studied an agent to bind interleukin 1 and subsequent inflammation. And they examined patients with previous MI and an elevated CRP of greater than or equal to two, similar to Jupiter, where the CRP, again, was greater than or equal to two. To me, this study provided definitive biologic possibility that inflammation is directly involved in the causal pathway and reduced cardiovascular events 15% without importantly influencing LDL or cholesterol levels, without influencing blood pressure, without influencing blood sugar. It turns out the drug was not studied further given the increased risk for infection. And quite frankly, the cost for the agent was just prohibitive. However, this is an important landmark study, really establishing a biologic possibility and the mechanism that inflammation is directly involved in the causal pathway. Ridker did this important Lancet meta-analysis. He took 31,000 patients on statin. The publication was performed in 2023 and looked at three databases from three randomized clinical trials, prominent with the fibrate, reduce it with the SIPA and the strength with a combination EPA, D8, A. Shown in the black, so now we're going to pull the data on the right, shown in black are increasing levels of high sensitivity C-reactive protein in quartiles. That was in black. Shown in white are increasing levels of LDL levels in quartiles. Then he compared the highest quartile, four, versus the lowest quartile, one, for high sensitivity reactive protein. And what they report is a 2.6 fold increased risk for cardiovascular death comparing highest versus lowest quartile. And conversely, if you look at the highest and lowest quartile of LDL, it was 1.27 fold higher, also important. And in this analysis, keep in mind that patients were on a statin. So they concluded that arguably inflammatory risk is a more powerful predictor of cardiovascular death than LDL cholesterol alone on statin treated patients. Remember, I asked the question earlier, if you have residual cardiovascular risk on statin, what's your next step? Next, the last two studies are also published in New England Journal. On the left is the trial called LODOCO-2, on the right is the study called COLD-CUT. So let's talk a little bit about LODOCO-2. They examined CAD patients who had been stable for at least six months. The study on the right looked at recent MI, less than 30 days. In both trials, patients were randomized to low dose colchicine, that's colchicine 0.5 milligrams versus placebo. Importantly, in the studies, they did not require measurement of C-reactive protein. They did have a subgroup of patients in the LODOCO-2 trial where 10% of subjects had the CRP level and the median level was between 3.5 and 4. This is going to be important because the actual indication for low dose colchicine does not require the measurement of a C-reactive protein, though many of us in cardiovascular prevention believe that this is how the drug works, through modifying the risk of inflammation. And based on a recent meta-analysis from these two studies and also a few other studies, including 12,000 patients, they have shown that colchicine reduces MI 25%, stroke 52%, and revess 39%, with no impact on cardiovascular death or all-cause death. And very importantly, it was found to be safe with no serious adverse events, and it was low in both groups. Next slide. So how long should we treat patients with low dose colchicine? In the LODOCO-2 trial, the investigators perform a landmark analysis where after each year, they set the counter back to zero advance. So you see four time periods here. Year one, there was a 32% reduction in cardiovascular events favoring low dose colchicine. You set the counter back to zero, and year two, you get a 32% reduction. And then you set the counter back to zero. And in year three, 39%, and then year four and five, 47%. So it appears that over time, the benefits appeared to increase, indicating perhaps we need to continue these agents lifelong, unless we have a cure for whatever you're dealing with. And certainly in the absence of advanced kidney disease or advanced liver disease, probably ought to continue these agents indefinitely, once you make the decision to initiate the therapy. Next slide. So in the 2023 AHA-ACC chronic CAD guidelines, they were published in August of 2023. And at the time, the drug was not yet approved by the FDA. So when the publication was made, the FDA had not yet issued a verdict. And they did acknowledge the role of colchicine in the guidelines, saying that it has a role, but we have to use caution given the narrow therapeutic window. And they issued a class 2B recommendation that usefulness and efficacy is less well-established. But at that time, the FDA had not yet approved the drug in the US. But fast forward to the next slide, which is hot off the press, literally less than four weeks ago in the 2024 European Society of Cardiology chronic CAD guidelines were just published. granted low dose colchicine, a 2A level of recommendation and a level A recommendation. So 2A recommendation, level A category to reduce the risk of MI, stroke and revast, exactly what the meta-analysis had shown. And again, to recall, class 2A means that the recommendations and weight of the evidence or opinion is in favor of treatment for usefulness and efficacy or both, all right? And very importantly, if there's a 2A recommendation to initiate therapy, they also said that, hey, it's a 2A recommendation to perhaps check HSCRP levels along with lipid profile, CBC, kidney function, A1C and blood sugar. So you can't know someone has inflammation unless you actually check it. So 2A recommendation, exciting times. So how do you go about in your algorithm? This is a slide where the data and recommendations were compiled by Dr. Paul Redker and his group, really recognizing dual pathways for cardio prevention. And so you have a patient with chronic atherosclerotic disease, you initiate statin therapy, and then you assess treatment response to LDL and CRP. And you really have four different pathways. We show you the three that involve treatment. So pathway one is your LDL levels, elevated CRP is not. So you have residual cholesterol risk and you initiate additional cholesterol agents. This is pathway number one. Pathway number three is your LDL is less than 70, but your CRP is greater than two and you have residual inflammatory risk. And then you may consider additional inflammation lowering agents. Path two is you have both elevated cholesterol and elevated CRP and consider dual pathway of reducing residual risk with additional cholesterol, treatment and inflammation lowering agents. And four would be both LDL and CRP are optimal. Now keep in mind when this came out, they didn't have the new recommendations for more aggressive LDL lowering of less than 55 and very high risk groups. And even a very, very high target of less than 40, but you get the point of how Rydker and his group kind of looking at how do we treat these patients? So keep in mind inflammation inhibition and lipid lowering are not in competition, but are fully synergistic therapies. And the best care might involve aggressive lipid lowering therapy combined with aggressive inflammation inhibition. I do want to point out that Lodoco 0.5 milligrams daily can be safely used in conjunction with statins, safely used in conjunction with Zadia or acetamide, safely used with bempidoxic acid and safely used with PCSK9 inhibition. It's a drug that could be used in complimentary. Next slide. I think this is an important slide. Sort of put my thought together. You know, how do you know who to check, when to check and how do you interpret the results? So if you were to take home a message from this presentation, I highlight two important variables to target. One, recurrent events. So they have their second event or multiple events. That should be a clue. Inflammation might have a role here. And then two, you check a CRP level. And for me, the magic number is greater than or equal to two and I'm going to say less than 10. If you get that, this is a patient at high risk for future events. I don't believe that we ought to target all patients to begin with, because there's so many other factors that need to be addressed. But when you're having a patient having recurrent or multiple events and their CRP level is elevated, you really need to think, hey, this patient has residual risk. What can I do to change their future trajectory for having a cardiovascular event? All right. So who to check? Recurrent events, multiple events. I'm going to say the more diffuse your CAD, the more diffuse your vascular disease. And certainly if you have diabetes as one of your risk factors, I would maybe even add maybe poorly controlled risk factors to who to check. When do you check? You check after an acute ACS event. You check after a coronary intervention with PCI or CABG. And certainly when the lipid profile is drawn. Remember, you can't assess inflammation until you have a lab test. You need to have an index of suspicion and check a CRP level. And I don't believe this is being routinely done yet here in the US. We have times to change and change our practice pattern. And the interpretation optimally, you want the high sensitivity C-reactive protein to be less than one. Elevated is considered a level between two and 9.9. And if it's greater than 10, this might be due to infection. And you might want to repeat the levels. In my practice, I've actually been able to make a diagnosis of a number of rheumatological conditions simply by paying attention to C-reactive protein. Keep in mind that patients with rheumatoid arthritis, patients with lupus do have higher rates of cardiovascular disease and cardiovascular events compared to those without lupus and those without rheumatoid arthritis. And so there's a direct link there. But if the level is really, really elevated, consider repeating it again. However, in my practice, once I initiate therapy, I don't then repeat it again to determine the level and follow-up therapy. So once you identify the risk, you initiate the therapy and you're done. You can choose to recheck a high sensitivity C-reactive protein if you're working on addressing other risk factors. But in my opinion, I don't believe it's man and it's, it determines management. And quite frankly, unless the risk is modified or reduced, I would not personally recheck another C-reactive protein. And that's subject to discussion. So next slide is looking at metabolism, drug-drug interactions, and safety. Lodoco is absorbed in the small intestines, metabolized in the liver by CYP3A4 and excreted in the kidneys and in bile. Lodoco is not recommended for patients with impaired renal disease. I'm gonna say stage 3B to stage 5, or if your GFR is less than 45, others say perhaps stage 4 and 5. I think as we're learning about this drug, it's reasonable to be a little bit more conservative. I would not initiate this drug if the GFR is less than 45, in my opinion, or anybody with impaired hepatic function, including liver cirrhosis. You can remember those two groups, impaired renal impairment, that's stage 3B or worse, or impaired hepatic function, including liver cirrhosis, I would not use Lodoco. Consider stopping the drug if you are to use an agent that's a CYP3A4 inhibitor or a B-glycoprotein inhibitor, like clarithromycin, ketoconazole, fluconazole, or cyclosporine, just a thought. This drug does not appear to increase risk for infection. This drug does not appear to increase risk for cancer. There's no apparent interactions with statins, although you might get a question from a pharmacist regarding the drug-drug interactions with a statin. It's been found to be safe. Certainly that was the case on the Lodoco 2 trials. And the most common adverse event is GI side effects, and it's a linear dose relationship, and then also neuromuscular and renal issues. Next, in the Lodoco 2 trial, serious adverse events were very rare when compared to placebo shown on, and this analysis is looking at important factors like new cancer, hospitalizations for infection, pneumonia, GI reasons, neutropenia, myotoxicity, and colchicine appear to be comparable to the placebo arm. I do want to point out that colchicine did have a protective effect at reducing gout. Next slide. Colchicine has a narrow therapeutic index to toxic range. What does this mean? Small differences in the dose that is effective and what can lead to a serious or toxic adverse event. So that window is narrow between what's considered effective and what can lead to serious or toxic adverse effects. And so shown in this analysis, for example, is looking at steady state serum colchicine levels in patients with normal and impaired renal function. And you can see that with the higher dose of colchicine, 0.6 milligrams, you put yourself at risk. And so a common question is, hey, can I just use the dose that's approved here in the U.S. with colchicine 0.6 milligrams? I do want to say a couple of things. The dose study for cardiovascular benefits and reducing cardiovascular events was 0.5 milligrams. We do have long-term efficacy and safety with that dose. The FDA did grant approval for the treatment of chronic ASCVD with the low dose of colchicine. And 0.6 milligrams, although you might say, hey, that's still pretty low, is actually 20% higher than the 0.5 milligram dose and might be potentially problematic in the elderly. It might be problematic in those with variable renal function. And quite frankly, it's not indicated, nor FDA approved to treat patients for the prevention of cardiovascular events. I practice evidence-based medicine. Proved to me that it's beneficial and I'll use the dose studied in the clinical trials. But this is subject to debate. I understand that people might have differences of opinion. I just present to you what I know and I would encourage you to use the drug safely. Because remember, these patients will be on this drug indefinitely unless you have a cure for whatever you're dealing with. And we need to keep the safety of this drug in mind. Next, this is a slide that came from the company. And for insured patients, the drug may be as low as $10 per month for a three-month prescription. I did go on a GoodRx. And in GoodRx, the colchicine dose for 0.6 milligrams was interestingly about, on average, $40 to $50 per month. So for insured patients where it's covered under your insurance, it might be as low as $10 per month for a three-month prescription. For uninsured patients or those where the insurance company does not cover the drug, it might be as low as $99 cash per month. And the treatment has to be sent to BlinkRx. And for indigent patients, I'm told the company has some sort of a patient assistance program. You can get the details on this website here, www.lodoco.com. I went on it just last night to see what it looks like. But the bottom line is, is that the company is working hard to get better insurance coverage. And so I think the more we write for the drug, the more coverage we will get to help our patients. It does take some time to get into certain formularies, but we have to fight for our patients. We're getting to the close here. Just a couple more slides. This is a slide I put together looking at CBD and pharmacological therapies to reduce residual cardiovascular events after statin therapies. You can see you have the statin therapy, so that's one drug, plus eight additional class one or two A recommendations as listed here with aspirin, ADP blocking agents, other cholesterol lowering agents, placebo, ACE, ARB, GLP-1, agonist, SGLT-2 inhibitor, and now Lodoco. And what a dizzying number of drugs we put our patients on. And what I would say is that there is one common theme. In my opinion, all these drugs, including statin therapies, reduce CRP. Interestingly, hormone replacement therapy actually increases C-reactive protein. Niacin is neutral to this. Maybe we ought to just look at CRP to determine whether a drug will be beneficial in the cardiovascular arena. But I fully understand we can't start on all these drugs. Certainly we don't want to start on all these drugs at the same time, and you have to determine where Lodoco fits in your treatment armamentarian. I do want to point out that once you're on statin therapy, improve at trial with the addition of xenamide, reduced cardiovascular events, 6%, the PCSK9 trials with Fourier, Spire, Odyssey, 15%, Cantos, which I showed you was 15%, but look at Colcott, look at Lodoco. If you have residual risk, you're on max tolerated statin, what's your next step? So think about inflammation. It might have a role for your patients. So just to finish up with a case, a 61-year-old with four major modifiable risk factors has the stent for the LAD, but comes to you because they have a second event with MI and PCI. They're in pretty good medical therapy. They're obese, their EKG confirms the old heart attack. Now you have lab data, right? So we have the lipid profile, the LDL is 71, but the HSCRP is four. What's your next step, folks? And so I kept this case generic and kind of general. I didn't want to actually say anything about the risk factors. I want to know are the risk factors really aggressively treated? You know, what's the blood pressure? What's the A1C? You know, what's the patient doing with lifestyle modification? I definitely want to get them in the cardiac rehab. Now, clearly the LDL level is elevated, so you can increase the dose of the statin. You might get a little bang that way. Do you add a Zedia or maybe a PCSK9 inhibitor? Or do you potentially address this issue of inflammation? And I would argue perhaps this might be a good patient to consider Ladocal as your next step. But there's a lot of things you can do. As you know, there's many different options for patients. And again, remind you the dual pathway for cardio prevention. After you initiate that statin therapy and have residual risk, what is your next step? Don't forget about inflammation. So in conclusion, lipid lowering is important in reducing cardiovascular events and statins is a cornerstone of therapy. Statin is the greatest revolution. However, inflammation is also a major predictor of future cardiovascular events as measured by high sensitivity CRP. Ladocal is approved by the FDA as the first and only anti-inflammatory drug for cardiovascular disease as of June, 2023. And low-dose colchicine, that's Ladocal 0.5 milligrams is effective, proven, safe option in selected patient populations. And just a reminder, Ladocal is not recommended for patients with impaired renal function at stage 3B or worse, or anybody with impaired hepatic function. Thank you for your time. Thank you for your attention. And I welcome any questions. Chris, have you back online? Dr. Canto, thank you very much. That was an excellent presentation. I want to remind everyone that if you go into the chat feature down at the bottom, if you hover over that, you'll be able to see the link for this presentation and you can download that. You can review it later. You can share it with colleagues, et cetera. In the meantime, there's also the Q&A button. We do have one question that's been submitted. And if you'd like to submit your question now for Dr. Canto or the AGIFA team, please submit it there. I do have one question, Dr. Canto, which patients are you treating with low-dose colchicine? Great question. Let's go back to slide 20, if we can. Might be, yeah, there it is. I believe this is an important slide because there's so many therapies you can pick for your patient. I always start out with a stat and I'll always start out with class one recommendations. But on the top line, recurrent events, that to me is a big one. And with that, an elevated CRP greater than or equal to two. I would say probably less than 10. If I get a recurrent event, elevated CRP, they're on my radar. They should be a candidate for Lidoco. And then if you want to add a little bit of a twist, you can add the more diffuse or atherosclerotic burden, certainly with coronary disease, vascular disease, a diabetic who typically presents to us with diffuse atherosclerotic burden and anybody with poorly controlled risk factors who, despite your best intentions, still has residual risk and your CRP level is elevated, man, you got to think about Lidoco. I don't believe Lidoco is a drug I would start out first line therapy if their CRP level is less than a two. Just keep in mind in the clinical trials, they did not require checking a C-reactive protein. But I've talked with Dr. Paul Redker and other experts in this area. Most of us are really reserving this drug for recurrent events, especially if the CRP is greater than or equal to two, assuming they don't have advanced renal failure or advanced liver disease. Thanks. Good question. Well, you must have done a very, very comprehensive presentation because that's all the questions we have at the moment. I'll continue to monitor it for a second. I do want to thank Ajifa Pharma for sponsoring this presentation. Dr. Canto, let me give you the final word. If you have any closing comments for the membership, all yours. Yeah, thank you, Chris. We're just fighting for our patients. If you want to make a difference in this business, it's all about treating and addressing residual cardiovascular risk. If you're on max tolerated statin, you're having a patient who's having recurrent events, what's your next step? I would encourage you to pay attention to all the risk factors. They all matter, but don't forget about inflammation. It really does matter. I hope I encouraged you to begin to think outside the box and maybe check a CRP because you cannot know about inflammation unless you check it and begin to help us move to the journey of knocking out and stamping out our disease. Thanks, Chris. Thank you, everybody, for your time and your attention. God bless you all. Bye-bye now. Thank you very much. Have a good day.

cardiac inflammation

cardiovascular risk

Lodoco

colchicine

atherosclerotic disease

C-reactive protein

myocardial infarction

stroke