Thank you very much, Dr. Paul. Welcome everyone to this educational activity based on something we interventional cardiologists may not do as much, and that is optimal prevention, secondary prevention for patients who already have established cardiovascular disease and how to manage their lipids. The objectives of our talk today include recognizing system-level gaps in the care of our patients who have had percutaneous coronary interventions, documenting and communicating across the care team to ensure that our patients receive optimal guideline-directed lipid-lowering therapy for secondary prevention, and empowering patients with knowledge necessary to make decisions about setting and achieving their target lipid levels. Next slide. So there are many gaps in our overall assessment of cardiovascular risk in patients with established cardiovascular disease. For example, only half of the patients who are undergoing PCI for an acute coronary syndrome have a lipid profile documented during their hospitalization. Only 35% of patients who had a PCI have a repeat lipid panel within six months of intervention, and a lot of evidence has shown that unless we are controlling their lipids quite well, they are at significantly increased risk of repeat events. Many PCI patients do not receive guideline-directed medical therapy. Many of them are not even on appropriate antiplatelets and not on statins. Tailoring therapy based on individual risk factors can improve outcomes of these patients and also reduce hospital readmission and re-hospitalization costs, particularly speaking for minorities and underserved populations have had a higher burden of cardiovascular disease and are even less likely than others to receive guideline-directed secondary prevention medical therapy. Next slide. There are many options for treatment of lipids. First and foremost are statins with a track record of decades now in reduction of cardiovascular events, particularly MI and stroke. ZMI is an important piece of that pharmacological option, armamentarium, PCSK9 inhibitors have been available for a few years now. In glycerin, which is SIRNA directed to PCSK9 inhibitors, PCSK9 receptors, omega-3 fatty acids and icosapent ethyl, which have strong data for mortality now, bempedoic acid, which again has shown improved cardiovascular outcomes in addition to lipid lowering, phenofibrates for triglycerides, and finally LDL apheresis for select patients. Next slide. So lipid goals in atherosclerotic cardiovascular disease have recently changed, and we as interventional cardiologists should be at the forefront of managing lipids in these patients, particularly in patients who are at very high risk of atherosclerotic cardiovascular disease. The target LDL based on the 2022 ACC expert consensus decision pathway is less than 55. It's not less than 70 anymore. It's less than 55. Both LDL reduction by greater than 50% from baseline and LDL goal of less than 55 has been part of European guidelines since 2019. Patients with diabetes and established cardiovascular disease target of an LDL cholesterol reduction of 50% from baseline and LDL less than 55 is also based on the new guideline from American Diabetic Association published in 2023. So all in all, we should be targeting a goal of less than 55 for patients who are at very high risk of atherosclerotic cardiovascular disease. Next slide. So which patients are the major risk patients? So patients who have had recent acute coronary syndrome within the past 12 months, history of MI other than recent ACS event ever, history of ischemic stroke, symptomatic peripheral arterial disease, such as those who have claudication with an ankle brachial index of less than 0.85 or previous revascularization of lower extremities or any extra or carotid arteries, for example, or history of amputation. So a lot of, you'll see that a lot of our patients that we see as interventional cardiologists fit this bill of having or being at risk of major cardiovascular events. High risk conditions also play a role, such as age greater than 65, heterozygous familial hypercholesterolemia, history of prior CABG or PCI outside of a major cardiac event, diabetes, hypertension, chronic kidney disease with a GFR less than 60, current smoking, persistently elevated LDL cholesterol greater than 100, despite maximally tolerated statin therapy and ezetimibe, and history of congestive heart failure, next. So the first line treatment to achieve the target LDL goal is to use a high intensity statin therapy or at least maximally tolerated statin therapy. That's a class one indication based on guidelines. If LDL is greater than 70 while on a statin, as a first line, add ezetimibe to the maximally tolerated statin. That's a class two way indication. And then when to add a PCSK9 inhibitor is the next major question. In very high risk patients, if LDL remains greater than 70 or non-HDL cholesterol is greater than 100 on maximally tolerated statin and ezetimibe, then PCSK9 inhibitors should be added. If LDL is greater than 55 while on statin in very high risk patients, consider adding ezetimibe or PCSK9 inhibitor to the maximally tolerated statin therapy. And then patients with statin intolerance are also good candidates to add PCSK9 inhibitors. Next. So here is a proposed algorithm which is based on the 2022 ACC Expert Consensus Decision Pathway. So I'll walk you through it. Patients who have established cardiovascular disease, that is, these are patients who have already had an event and now we are talking about secondary prevention. We should be checking their LDL level. If they are not on a high-intensity statin, then they should be on a high-intensity statin, which, by the way, includes only two statins, atorvastatin at a dose of 40 to 80 milligram or rosuvastatin at a dose of 20 to 40 milligram. We should be rechecking their LDL levels within six weeks. As I alluded to earlier, only 35% of patients get a repeat lipid profile in six months. And our current guidance says that we should be rechecking LDL levels within six weeks. In patients who are at very high risk, to the right side of the cartoon here, if LDL is now less than 55, great, continue that. If the LDL still is greater than 55 at six weeks, then consider adding PCSK9 antibody or even could consider bampydoic acid or in glycerin as a second-line therapy. In patients who are not at very high risk, if their LDL is less than 70, then you can continue statin and check LDL annually. In patients whose LDL is still above 70, then add ezetimibe. If their LDL gets to below 70, great, you can continue statin and ezetimibe and check their LDL annually. If the LDL is still greater than 70, then consider PCSK9 inhibitor. Now it's important to reassess LDL in six weeks or annually, depending on where they are. Once the patients reach their target, then it is okay to check it once a year, but until they have not made it to their target LDL based on their risk, then their LDL needs to be checked much more frequently. Next slide, please. Statin therapy, it is important to understand that high-intensity statin therapy, that is the high doses of atorvastatin and nusuvastatin that I just mentioned, it lowers the LDL by about 50% or greater. moderate-intensity statin decreases LDL by 30 to 49% and low-intensity statins by less than 30%. And I'll show you how much each statin does here in a moment. Randomized control trials have consistently demonstrated that statin reduces the risk of major events by 21 to 23% for each millimole reduction in LDL during each year after the first that it is taken. You can see a very major decrement in the incidence of cardiovascular events in patients who are on maximally tolerated medical therapy and maximally tolerated statin therapy in reduction of hard cardiovascular outcomes. The benefit of therapy depends on the individual's absolute risk of ischemic events and the absolute reduction in LDL cholesterol. Statin therapy reduces vascular disease risk also during each year of continued therapy with persistent long-term benefits. Next slide. So here is a graph that shows how much we expect the LDL to go down with each statin. So as you can see in green, that nusuvastatin, 20 to 40 milligram, or atorvastatin, 40 to 80 milligram, is what reduces LDL by about 48 to 55%. And the ones in yellow are the moderate intensity statins, which reduce the LDL by about 30 to 45%. And then low intensity statins reduce it less than 30%. And with this, I will hand over to Dr. Paul.

lipid-lowering therapy

statins

PCSK9 inhibitors

LDL levels

atherosclerotic cardiovascular disease