Thank you, Dr. Paul, and Dr. Lateef and Dr. Paul have set the stage nicely for me to talk about some of the other agents that were already mentioned, but I'll provide a little bit more granular detail. So intliserine is essentially a PCSK9 inhibitor. It's not an antibody. It's a small interfering RNA, which reduces the hepatic synthesis of PCSK9. Again, like PCSK9 inhibitor antibodies, it's add-on therapy typically for patients on maximally tolerated doses of statin, and typically with or without ezetimi. Very robust reduction in LDL levels, similar to PCSK9 antibodies, and really no significant side effects except for injection site adverse events. It was approved about two years ago, and the dose is 284 mg sub-Q injection day one, day 90, and then every six months. So that's an advantage to the antibodies because the injections are less frequent. I think the key part, key message from this webinar is how do we work together with our patients, our referring physicians, to optimize secondary prevention and reduce cardiovascular events, and our panelists will discuss it in more detail. But I think a key way to do this is to empower our patients, and having a checklist for your patients, giving it to them as your healthcare provider, talk to you about lifestyle changes, which are key. Exercise, cardiac rehab in appropriate patients after an MI or after revascularization, diet. Are they treating your risk factors? Hypertension, diabetes, obesity, other conditions. Has somebody mentioned to the patient their personalized risk using a risk calculator, a CVD risk calculator, reducing risk through diet, exercise, if they're smoking, quitting smoking? Whether cholesterol levels are adequately controlled, and Dr. Lateef mentioned the optimal LDL level today is 55, not necessarily 70 for high-risk, very high-risk patients. The need for medications, and if applicable, how therapy is given in addition to statin, how much they cost, the potential drug interaction. Need for lipid panel, and only about a third of our patients get repeat lipid panel. Do they have a hereditary risk of hypercholesterolemia or either homozygous or heterozygous? Certainly homozygous statins are not going to work, and you need PCSK9 inhibitors. And for that very difficult patient where you have tried everything, including statin, azitomy, PCSK9 inhibitor, their lipids are still suboptimal, maybe the referral to a lipid specialist. On the right side of the slide, we have the agents that have been mentioned, and I'm not going to go in detail over everything. So basically, we have five agents right now, statins, azitomy, the PCSK9 inhibitor antibodies, inglycerin, which is a PCSK9 inhibitor, but a small interfering RNA, and bemphidoic acid. Statins are very effective. Dr. Lateef showed certainly high-intensity statin, 40-50% reduction in LDL. They're not very expensive today, particularly the generic forms. They can cause some side effects, muscle pains, liver problems, rarely difficulty speaking, sleeping, increased blood sugar. And as I said, they are less expensive than the other agents. Azitomy, relatively more expensive. It's oral. It reduces cholesterol absorption, and it is once a day. It's not as effective as statins or some of the other agents, 10-15% reduction, mostly GI side effects, diarrhea and GI dyspepsia, abdominal pain, sometimes muscle pains. PCSK9 inhibitors, Dr. Paul went over some of the data, very effective, 50-60% reduction. They're actually fairly effective in reducing lipoprotein A also. And in some of the PAD studies, lipoprotein A lowering was a more important predictor. Injections are every two to four weeks and can be done by the patient. They are expensive and will go over. They do need preauthorization to be paid by the insurance companies. Inglycerin is a PCSK9 inhibitor, also expensive. The injections are less frequent. The side effects are more local, muscular pain at the site of injection, sometimes trouble breathing. Bempedic acid is the newest kid on the block. Dr. Paul did go over it. It's, again, for statin intolerant patients and also for individuals whose LDL is still suboptimal despite being on statin and zetimibe. It's also an expensive agent and side effects are muscle spasms, diarrhea. So in the patient journey, secondary prevention, patients come to us as an interventional cardiologist with a coronary event, typically a heart attack or chest pain or chronic coronary artery disease, and their initial treatment could be most of the time it's PCI today, stenting with a drug-eluting stent or sometimes bypass surgery. But very importantly, we need to work with our patients, our referring physicians, and we'll hopefully discuss this in a little more detail, how do we work with a referral cardiologist if we are not prescribing ourselves this medication, how to involve the patient, but making sure the cardiologist discusses the risk with the patient, comprehensive risk factor modification, medications to reduce LDL-C, and potential use of a zetimibe, PCSK9 inhibitors, or bampydoic acid. It is key, as Dr. Lateef said, to monitor LDL to make sure for two things, that we are controlling LDL appropriately in the 50s. Also, there is compliance. Discuss any side effects, adjustment of medications to get to the target LDL, and monitor risk factor modification. PCSK9 inhibitors are expensive. They do need prior authorization and denial appeal. Prior authorization require that healthcare practitioners provide and document the following data for medication approval. We need insurance companies will ask for their most recent lipid panel. You have to document that they are not at goal. LDL, despite maximally tolerated statin with plus minus a zetimibe, and I want to clarify, maximally tolerated statin therapy sometimes can be zero statin. Some patients, we all have patients that do not tolerate any statin, even in the lowest dose, but I want to emphasize, if they're not tolerating high intensity statin, even low dosage of moderate intensity statin is better than no statin, but there are occasional patients who don't tolerate anything, and certainly very reasonable to go to PCSK9 inhibitors in those patients, and history of statin intolerance if they are not on maximally tolerated statin therapy. I'll share with you a template form that was published in clinical cardiology on how to get pre-authorization. If authorization is denied, the appeals process enables clinicians to petition, change in insurance provider's decision, and I'll share with you also an appeals letter template. So this is a typical prior authorization template from clinical cardiology. You have to document that the patient is taking maximally tolerated statin, or if they are not on any statin, then you document that they're intolerant, you document their diagnosis of ASCVD, and either heterozygous or homozygous familiar hypercholesterolemia, and that the patient does have clinical ASCVD. Not going to go over the entire template, but you document what kind of ASCVD they have to justify the insurance company paying for PCSK9 for secondary prevention. In case your petition gets denied, you'd appeal that denial. You again document that they have homozygous, heterozygous familial hypercholesterolemia, they are on maximally tolerated statin, they have clinical ASCVD, they require additional LDL lowering based on the guidelines that we need to get them to 55 or lower and you send it back to the insurance company. So we have to satisfy the indications for use, and we have to document all clinically relevant information for peer requirements, use a PCSK9 inhibitor prior auth form in your practice, you can use the template, modify it. If you have samples in your practice, start the patient. If denied, appeal. Act on the decision of the peer-to-peer. If you're denied, ask for a peer-to-peer so that you can talk to a physician to convince it. Engage the patient. They can call their insurance company, and if you have samples, keep the patient on samples. The patient is the most important individual here. If appeal is denied, request a peer-to-peer. Keep fighting for your patient. Deploy social media. Ask the patient to post comments on Twitter, Facebook, pushing the insurance company about the denial. And don't give up. Encourage the patient. Continue to work with the insurance company. These agents not only robustly lower LDL, but they reduce cardiovascular events significantly. There are some patient resources programs. Work with your clinic manager or your allied health practitioners. These are Repatha Ready, MyPraluent, LegvioCare program to see if your patient qualifies and may get the medication either free or subsidized so that we take care of the patient. And finally, I do want to mention fenofibrate. It is a triglyceride-lowering agent and added for the treatment of hypertriglyceridemia if other measures fail, including lifestyle modification, management of secondary factors like diabetes, chronic liver disease, if they have failed, omega-3 fatty acids. And between the two agents available for lowering triglycerides, fenofibrate is preferred over gemfibrozil when combined with the statin, given the lower risk of severe myopathy. And the clinical trials have not shown that fenofibrate reduces cardiovascular mortality, but they have a modest effect on cardiovascular events reduction in patients receiving statin.

agents

secondary prevention

PCSK9 inhibitors

insurance coverage

fenofibrate