Hello, and welcome to another episode of The Tell-Tale Heart, Pharmacy Times' cardiovascular digest for pharmacists. I'm your host, Craig Beavers. As always, before we get into the guests and conversation, if you like our content, like, subscribe, and give us feedback. We're always trying to add, change, modify, and get new guests, so please let us know.

I have an exciting episode today. As you may see from the studio, we are here at the National Lipid Association (NLA) meeting in Orlando, Florida, for their update meeting. We're partnering today with the Lipid Insights podcast, the NLA podcast, and I'm very excited to have our guest with us today. I've worked with him a lot; he's a great colleague and peer, and I'm excited to get his perspective as a lipidologist and an expert to bring to you, the pharmacy audience. So, I'm going to allow him to introduce himself. Dr Michael Wilkinson, would you like to introduce yourself, where you're at, and what you do?

Sure. Well, thanks again for the invitation. Great to be with you. I'm Michael Wilkinson. I'm a cardiologist and an associate professor of medicine at UC San Diego, and I run our lipid clinic there, our Advanced Lipid Disorders Treatment Program.

Very good. Since we're here, and it's been such an exciting year for lipid management, I think the obvious topic of change, or at least update, to provide a foundation for our conversation is the new set of guidelines that came out within the last year. Briefly, thinking about it as a lipidologist, what are the highlighted changes you would like to share from your perspective that a pharmacist would be interested in, whether they've looked at them or not? What are the big things that have changed for practice, and how do you contextualize those?

I think 2 of the biggest things to come out of the updated guidelines are the way that we approach risk stratification, and then the way that we choose treatment targets and how to get to those targets. From risk stratification, that's the introduction of the PREVENT equations into our dyslipidemia guidelines, the PREVENT atherosclerotic cardiovascular disease (ASCVD) equations. Then, according to our assessment of risk with those equations, with other risk-enhancing factors, and with use of imaging like calcium scoring, we choose treatment targets for LDL cholesterol (LDL-C), non-HDL cholesterol (non-HDL-C), and in many cases apolipoprotein B (ApoB) as well.

Very good. Just to give some context, when the guidelines came out, we did an episode with Dave Dixon and Joe Saseen, who were on the guideline writing committee, and walked through the nitty-gritty of this. But as a refresher, when you think about PREVENT, I always like to remind people there are a couple of different versions of PREVENT. You've got to make sure you're using the ASCVD risk score version. What do you see as the benefits as you have that conversation with your patients about using PREVENT now vs when we used the ASCVD risk score?

I have shared with patients and with colleagues since the guidelines came out that these are revised risk estimates derived from a larger number of patients and from different sources. So it's really an expanded tool that I think is even more representative of the population we care for. It also sets new thresholds for how to think about risk. So it's important to understand how the 10-year risk estimates and associated recommendations for treatment have shifted. Those borderline, intermediate, and high-risk zones are a little bit different now in terms of the percent estimates for 10-year risk. But overall, it incorporates more information about the patient. There are more variables, and there are the optional variables that add even further refinement to that 10-year risk. So I think those are some of the advantages.

PREVENT obviously has a lower age threshold. How are you approaching that younger population now that you have a lower age threshold?

That's a great question. I think that for those younger patients, the 10-year risk estimates from PREVENT are still useful, but they're often low. Much like we had with the pooled cohort equations, a lot of the weight of that risk estimate comes from age, so we're still getting relatively low 10-year risk estimates for younger patients. But I think the 30-year risk is very helpful, and being able to apply that to younger patients is also helpful—

—to provide that conversation. It's interesting; tomorrow I'm doing a talk here at NLA around shared decision-making, and this is obviously a key part of that. Having that type of conversation is what your shared decision-making with your PREVENT score is, and I assume that's how you're incorporating it into your day and flow.

Yes, and I think the way to frame it for younger people is often with that longer horizon in mind. A 10-year risk estimate may only mean so much to somebody in their late 30s, so setting the conversation around your 30-year risk or lifetime risk—that's really what we should be talking about when we're counseling patients on the importance of lipid lowering over time. We know that the benefits come from lowering LDL and other pathogenic lipoproteins and keeping them at those lower levels over time. So we're talking about lifetime risk reduction, and framing it that way, I think, is really important for everybody.

Absolutely. I think it's gaining steam, and we all need to think more about that long-term exposure, and not just that this is a point in time and a fixed process, especially as we recognize more and more that there is this longer-term exposure and there's risk established. It's interesting; you probably saw the study at the European Society of Cardiology (ESC) Congress where they did CT scanning among all the patients and correlated it with various risk scores. The risk scores do a decent job, but there's still evidence of disease well before what we see in some of the risk scores, even in that younger population, and that carries risk to some extent, right?

Yes, I agree. I think overall we need to do a better job of how we frame that conversation for patients. In a lot of cases, it's not the best approach to wait until somebody's age is high enough to push their 10-year risk into a treatment threshold. If there are other risk factors, risk-enhancing factors, or imaging evidence that suggests somebody's at a higher risk of disease over that 30-year horizon or lifetime estimation of their risk, we should be intervening earlier.

Sure. I want to get to thresholds in a little bit, but one of the risk-enhancing features that came up in the guidelines, and really made a dominant splash, was the conversation around lipoprotein(a) [Lp(a)]. If you don't mind, briefly talk about what the suggestion was. Then, obviously, in the last several weeks we've seen preliminary data come out from Novartis' trial suggesting that it did lower Lp(a), but with no benefit. So, a twofold question: Tell us about Lp(a), what the risk is, and what it is. And then, in light of the data we have, how are you having that conversation with your patients now in terms of Lp(a)? Then I'll have a secondary question. Let's start there.

Sure. I think it's important to separate these into 2 Lp(a)-related topics. We'll talk about Lp(a) and its importance as a predictor of cardiovascular risk and its incorporation into the updated guidelines, and then we can talk about the development of Lp(a)-lowering targeted therapies.

Absolutely.

For the guideline update, what you're alluding to is the recommendation for universal screening for Lp(a) for adults. That was in the 2026 dyslipidemia guideline update. The NLA had a recommendation for universal testing in 2024, but this is the first American College of Cardiology/American Heart Association (ACC/AHA) multisociety recommendation that every adult should have their Lp(a) level tested once. This stems from the really large body of evidence that we have to support the role of Lp(a) in promoting atherosclerotic cardiovascular disease and calcific aortic valve disease, and it is a highly prevalent, primarily inherited risk factor. So for most patients, all it takes is to get your Lp(a) measured one time. It's genetically determined, so if it's elevated, it will have been that way essentially since you were born.

Can you remind people what an elevated number would be?

The guidelines specifically call out 2 thresholds for really beginning to worry about Lp(a)-related risk, and that's at levels at or above 50 mg/dL, or 125 nmol/L. Elevated Lp(a) is defined as above 30 mg/dL, or 75 nmol/L, but it's that higher threshold where we really begin to see more of a clear association between high Lp(a) and future risk. If we're just talking about that higher-risk range above 125 nmol/L, we estimate that affects about 1 in 5 people worldwide—20% of the population with a high Lp(a). But in the US, for example, we test less than 1% of the population for Lp(a). So what the guidelines are saying is that we have this highly prevalent, inherited risk factor for cardiovascular disease that we're not testing very often, and we need to change that. We need to make that a standard part of our risk assessment for our patients.

Okay. We'll allude to this in both domains as we carry through the conversation, and we can talk about the treatment targets in a minute. But how have you and your team begun to implement this process? To your point that we're only testing about 1%, what are some strategies to do that? And to lump this in, have you adopted the PREVENT score? Have you seen success with people taking up and using PREVENT at this stage, and how is that going? So, a little bit about how you're implementing these tools.

We're starting to use PREVENT. I'm seeing it more and more in my daily practice. It's become available as a dot phrase in our electronic health record (EHR), so I'm starting to see primary care and my other colleagues at UC San Diego use the PREVENT score and put it in their progress note when they see a patient. So we're seeing uptake of PREVENT.

For Lp(a), how do we bridge that gap between less than 1% of people tested and 1 in 5 people affected? I think we need a multipronged strategy to get there. Having a guideline recommendation suggesting that every adult be tested goes a long way. It's a good start. The messaging is very clear now: everybody should be tested for Lp(a). But I think there are some barriers that remain to implementing that recommendation, and those include things like access to tests and interpretation of the results, so people being comfortable with how to interpret results and incorporate those results into an assessment of a patient's risk. Confusion surrounding different units of measurement for Lp(a) is another thing the field has struggled with because, as I just said, there's mg/dL and nmol/L. Everything we're reporting out is in both of those units, so if you have different health systems and different clinics using different labs and different units of measurement, patients are getting information back that can sometimes be confusing. The same is true for clinicians, who may get Lp(a) back in mg/dL from one lab and nmol/L from another lab.

I also think that there's been some concern that even if you know your Lp(a), what can you do about it? Without a targeted therapy to lower Lp(a), is it actionable? I think it is very actionable, and I think the guidelines speak to that. The guidelines say very clearly now that if you have elevated Lp(a) above those higher-risk thresholds I mentioned, the first step is to identify and treat all other modifiable risk factors for heart disease. I don't think there's any arguing that Lp(a) is clearly a predictor of higher risk for atherosclerotic cardiovascular disease and, as I mentioned, calcific aortic valve disease. If you have high Lp(a), your risk for those things is higher. We're not sure yet if we can completely offset Lp(a)-related risk, but the way to start getting at that overall risk for a patient is to treat those other modifiable risk factors. So if you know Lp(a) is high and you know a patient is at higher risk, that does change your management. It's actionable because you'll begin to take an even more intensive treatment approach to things like LDL cholesterol, blood pressure, glucose control, and other cardiometabolic risk factors. That's the way I think about how to incorporate it now. And I think that messaging is something we really need to get out to more people, more clinicians, and more patients, because the message that this is something worth knowing now—that's actionable now—is a big part of overcoming that gap between the recommendation for universal testing and currently low testing rates.

Absolutely. To your point, I think we see this a lot. You end up testing someone with Lp(a), and, to your point, adjusting or modifying the other things we can do. There are a lot of people who, even before you think about Lp(a), haven't had their other things optimized or managed, like their other lipids—getting their LDL to the appropriate goal. We'll talk about goals shortly. We've got to do the basics first, right? So I agree with you.

Yes, and there's evidence that the basics do help in patients with high Lp(a). We have some nice studies, for example, looking at the impact of achieving Life's Simple 7. If you have a healthier diet and lifestyle, even if you have high Lp(a), we do see some meaningful reduction in risk.

Yes.

It still matters to do these things to lower your risk of cardiovascular disease when your Lp(a) is high. It goes a long way toward reducing your overall risk, and we see that with lowering of LDL cholesterol and other ApoB-containing lipoproteins. Clearly, doing that lowers cardiovascular risk in all of our patients at risk, including those with high Lp(a).

Correct. So the messaging there, and I'm glad you reiterated it, is yes: always lifestyle—recommending lifestyle activities to our patients, continuing to promote those, and helping them achieve that—and then, of course, starting with LDL, making sure we're achieving those targets and applying those therapies appropriately. As we were alluding to, the second part of the question is, what about therapies that modulate Lp(a)? What is your feeling, plan, or trajectory at this particular juncture?

Before diving into the HORIZON trial, I just want to point out that for Lp(a) therapies, there is 1 currently available FDA-approved therapy for Lp(a), and that's lipoprotein apheresis, which has an indication in select patients. It's important to point out that for individuals with Lp(a) of 60 mg/dL or above who also have established cardiovascular disease and familial hypercholesterolemia (FH), there is an FDA-approved indication to use apheresis to treat Lp(a).

The other thing in the guidelines that I think is worth emphasizing is the potential role of using PCSK9 inhibitor monoclonal antibodies in patients with high Lp(a) and established ASCVD who are not already at their LDL-C and non-HDL-C treatment targets with statins. Now, whether you consider a PCSK9 inhibitor an Lp(a)-lowering therapy is something we could discuss. It does have up to about a 20% to 25% reduction in Lp(a), but really, where those guideline recommendations come from are post hoc analyses of the PCSK9 inhibitor monoclonal antibody outcomes trials, so FOURIER with evolocumab (Repatha) and the ODYSSEY OUTCOMES trial with alirocumab (Praluent). In post hoc analyses looking at those participants with the highest Lp(a) levels, those individuals did significantly benefit from the use of PCSK9 inhibitors. They experienced significant risk reduction for recurrent events, as was the takeaway from those trials, and there was a signal that maybe some part of the risk reduction was attributable to changes in Lp(a). At the end of the day, the take-home from those trials, and I think it's why it's in the guidelines, is that those drugs worked for those patients. If you have a patient with ASCVD who is on a statin, is not yet at their LDL-C or non-HDL-C goal, and has high Lp(a), we can point to data saying that those patients will benefit from PCSK9 inhibitor monoclonal antibodies as an add-on.

Right.

That's what we have to work with today for Lp(a), in addition to, as I mentioned, generally managing cardiovascular risk factors. But the field of Lp(a)-targeted therapies includes pelacarsen in the HORIZON trial, and it includes many others, primarily RNA-targeted therapies. Pelacarsen, for example, is an antisense oligonucleotide. That's one form of an mRNA-targeting therapy. It targets and leads to the degradation of the LPA mRNA, the mRNA that codes for the apo(a) that's required for assembling the particle. Other drugs in phase 3 cardiovascular outcomes trials that are also RNA-targeted therapies for Lp(a) are olpasiran and lepodisiran. Zerlasiran completed a phase 2 trial but isn't in phase 3 like olpasiran and lepodisiran. Those are small interfering RNAs (siRNAs), and we can talk a little bit about how those are different from an antisense oligonucleotide, but the key differences are things like the frequency of dosing and the efficacy of Lp(a) lowering. There's also an oral therapy, muvalaplin, which is in a phase 3 outcomes trial. This is a drug that disrupts the binding between apo(a) and the rest of the Lp(a) particle, so it prevents that final step, the assembly of the particle. That drug has been shown to lower Lp(a) levels by about 80% or so, maybe a little bit higher, and it's in a phase 3 outcomes trial, as I mentioned. So that's the current landscape of Lp(a)-targeted therapies in late-stage trials.

In interpreting the results of the HORIZON trial, to preface, we don't have—

—all the results yet.

Thank you. We have the topline result, and what we know is that the trial failed to meet its primary endpoint. That is specifically what we know about the topline result of HORIZON. I'm happy to go into—

No, I think the big thing, to your point—you set up a very good stage. We have lots of therapies under investigation. This one particularly failed to meet its topline result. We know it changed levels; we did get informed of that. But we don't know what the complete data set looks like, and right now it's all a little conjecture because we don't have that data. Did we maybe pick the wrong population? Is it something else? Of course, we can't fully say until the data come out, but I think it's going to be an interesting conversation. Maybe my better question for you, and you've already answered it, is that people shouldn't be scared away from Lp(a) at this juncture just because of this topline result, right?

Right. I think that's 1 very important takeaway: everything we've been discussing about the robust evidence behind Lp(a) as a contributor to risk of cardiovascular disease, its heritability, the importance of knowing your Lp(a) measure and using that information to make treatment decisions, and just globally lowering your cardiovascular risk—all that holds. I think we are still in the stage of figuring out whether going after Lp(a) with a targeted therapy adds to the risk reduction we can achieve with the other interventions we use to lower somebody's cardiovascular risk.

What I do think is important for listeners to appreciate are some of the distinctions between HORIZON and the other outcomes trials I mentioned. It's important to understand that not only are the drugs different in terms of their mechanism of action—the antisense oligonucleotide vs the siRNAs vs the oral inhibitor—but, like you alluded to, there are differences in trial population. Whether that will lend itself to further interpretation of HORIZON when we have the full data, we'll see. But at least for now, we can say that HORIZON was a trial of patients who'd had a cardiovascular event—either a coronary event in the past, ischemic stroke, or peripheral artery disease (PAD)—and the primary endpoint for HORIZON was the composite of 4-point major adverse cardiovascular events (MACE), looking at death from cardiovascular causes, coronary events, ischemic stroke, and PAD events. And as you mentioned already, we know that the drug effectively lowered Lp(a) by about 80%. So what can we take away from a trial that didn't meet its primary endpoint? With that information, we know that in this population of patients with established cardiovascular disease, a drug that lowered Lp(a) by 80% didn't reduce the risk of 4-point MACE.

More to come, right?

If you look at the other trials—

Yes.

—they include slightly different, and I think importantly different, patient populations. I mentioned olpasiran in a phase 3 outcomes trial, OCEAN(a)-Outcomes. It's essentially a coronary trial. For inclusion, participants need to have a history of coronary artery disease, but it doesn't include stroke or PAD as part of the entry criteria, and the primary endpoint is a composite endpoint for coronary events. The Lp(a) for inclusion is a little bit higher, and olpasiran is a different drug, dosed every 3 months as opposed to once a month, with overall greater Lp(a)-lowering efficacy. Finally, both lepodisiran and olpasiran are being studied in high-risk primary prevention, which would be brand new.

Right. That may be the key, right? We don't know.

We don't know, but I'm glad that we're going to be looking at not only the HORIZON population, the high-risk secondary prevention population, but also primary prevention.

I think that's great, to continue to move the needle back toward our lifetime exposure risk—really thinking more about lifetime exposure and how we look at that and mitigate it. It's so refreshing to be looking at it in that domain. I get that as people are researching and developing, picking a very high-risk population mitigates a little bit of the risk in development, because you can definitely get the events you're looking for, along with all the logistics of doing a research study. But it's refreshing for us to look at this from a primary prevention lens.

Let me pivot to a little different question. I want to hear how you approach this. I think this is an interesting construct that you always work with: disease states that are inflammatory. We can talk about inflammation as a whole if you want to put that lens on it. But if you have a patient who has a history of HIV, rheumatoid arthritis, or something to that effect, we obviously know that enhances their risk for events. How are you contextualizing that, especially with the scoring system or other things? How do you put those inflammatory diseases in context, either when you're having a conversation with a patient or if you're going to treat them?

That's an important question. It's part of what we should be thinking about when we're seeing a patient and really trying to understand everything that can put them at risk for cardiovascular events. Those conditions fall outside of something like the PREVENT ASCVD equations and are included in the guidelines as risk-enhancing factors. So it's up to us as clinicians to find a way to incorporate that inflammatory risk into our overall assessment of that patient's risk and tailor our treatment recommendations accordingly. I think that overall, we should be intensifying treatment and setting more intensive treatment goals for individuals with some of the inflammatory diseases you mentioned—autoimmune or other inflammatory diseases where we know there's an increase in cardiovascular risk—and there's evidence to suggest that we can reduce that risk through more intensive lipid lowering. Lowering LDL cholesterol or other ApoB-containing lipoproteins may not be getting directly at the inflammatory risk as far as underlying mechanisms are concerned, but we know we can offset overall cardiovascular risk with more intensive lipid-lowering therapies in those patients with inflammatory risk.

Outside of the setting of a known systemic inflammatory disease or something characterized by chronic inflammation, we do use high-sensitivity C-reactive protein (hsCRP) for risk stratification. That's in the updated guideline recommendation. So using an hsCRP measurement and finding that it's over 2 mg/L on more than 1 measurement, you can use that as another flag of a patient at higher overall risk. You have now identified some chronic, low-grade inflammation that may be contributing to overall risk. As for what to do with that from a pharmacologic perspective, I don't have a straightforward approach currently, but I think it tells us more about an individual's risk. I think it's often tied in with other cardiometabolic risks—things like overweight, obesity, metabolic syndrome, diabetes, and inflammation. So it's helping us to have a more comprehensive picture of that patient and their risk.

I appreciate you saying that. That's really what I wanted to get toward. Talking about treating inflammation is a separate can of worms that we won't kick open today, because there are other trials and other things involved; that's for another day. What I really wanted to get to, and you did this beautifully, is how you contextualize that with the patient. I'll give you a generic case example. You have a patient with an intermediate-risk PREVENT score, maybe they have an elevated Lp(a) like we were just talking about, and they also have a history of controlled HIV. Where are you now? Are you going to recommend they get a coronary artery calcium (CAC) score? Are you going to go ahead and push them toward treatment? How do you approach that patient who's intermediate for everything and maybe hesitant? What is going to help you do the shared decision-making process to lead them that way?

It's such a critical question. That is our everyday. That's the moment for us to have that conversation—that shared decision-making with the patient—where there is some uncertainty, or where we need to meet the patient where they are in thinking about their risk or their readiness to do something like start a statin or other lipid-lowering therapy. So I think it really does depend on how that conversation goes. We can use things like estimates of 10-year risk for ASCVD; is that helpful in the conversation with the patient? Is describing their risk more generally, in terms of the fact that we know inflammation is a risk-enhancing factor, enough to make that decision together? Often it is. If you say, "These are the guideline recommendations. I think you'll benefit from this. It will lower your 10-year risk and your lifetime risk of having a heart attack or stroke," I think that's often enough for that conversation.

But I also think there's an important role for things like coronary artery calcium scoring as a tool for further risk stratification and often for further individualizing that risk assessment. I think it is very helpful for that. It's always important to interpret coronary calcium scoring results with the individual patient in mind, though. Some patients are not as well represented in some of the studies that have been used to determine how we incorporate calcium scores into an estimate of risk. For example, in these cases of patients with systemic forms of inflammation, we know less about how a calcium score may perform than in the general population of patients more broadly represented in the cohorts used to understand how calcium scoring helps modify that assessment of risk. That said, I think a calcium score is one of the most useful tools we have today for cutting through some of the uncertainty that often comes with risk calculators and with our ability to, oftentimes qualitatively, incorporate risk-enhancing factors. If you have a calcium score of 0, that means something. If you have a nonzero score, that means something too, and how high that nonzero calcium score is means something, even if the estimates lack precision for an individual patient's situation. It still gives us, I think, a very useful tool to move that patient into different levels of risk.

Very good. Let's transition briefly. We won't go into every new threshold; we talked about that very heavily in the previous episode, and I refer people back to my conversation with Dave and Joe when the guidelines came out regarding the new thresholds. But more generally, at a high level, what is exciting, or maybe rejoicing, for you about going back to threshold-based targets? And going back to my implementation question, how do we get people back into that mindset and working in that direction?

I think it's a great thing for the field. I think it's going to lead to more of our patients being treated, and treated to lower targets—lower levels of LDL cholesterol than you might otherwise achieve if your goal was to start a certain intensity of statin therapy. We now have a lot of tools that can help us get patients to lower levels of LDL cholesterol and related lipoprotein targets, and I think it's now in line with the totality of the evidence we have around the benefits of lowering LDL cholesterol and these related measures for preventing heart disease.

Right.

So I'm very grateful for the reintroduction of these targets, and I think from an implementation standpoint, it's going to be helpful. I think everybody—clinicians and patients—benefits from having a target, something we're reaching for.

Have you already adopted or made your own quality metrics around this? I know at some point we will probably have value-based metrics or something that ties back to this, but being proactive, have you already implemented some quality-based metrics around achieving these targets?

Yes, I've seen that come through at UC San Diego just within the past couple of months. At least our own internal measurements are being reported along with other quality measures. There's an LDL in secondary prevention measure that we're measuring.

Very good. I have 2 more questions, and then we'll near the wrap-up. Obviously, one of the other big things this year is the first oral PCSK9 inhibitor that has come out. How are you thinking about when and where you're choosing an oral agent vs an injectable? I have my own perceptions and commentary, but when you're in clinic now, what is your approach or conversation about this, and how are you deciding which avenue to go down?

It's a great question, and something that comes up every day. We have a lot of tools to work with, which is amazing. It's a great time to be in this field and be able to respond to an updated guideline recommendation that we need to get patients to goal targets, because we have really effective tools to get there. We need to use them.

With PCSK9 inhibitors, the way I usually frame it for patients is based on things like their treatment target and how far away we are from it, given that there are some differences in the expected efficacy of the different PCSK9 inhibitors. A patient's preference for an injectable vs an oral therapy is important, plus the frequency of injections; all of those come into play. The adverse effect profiles are things we talk about as well, and then, frankly, access is a big one. We talk about the differences between these drugs, the data behind them, and their efficacy and safety, but at the end of the day, what can you actually access? What will your insurance approve? What will they help pay for?

I think the oral PCSK9 inhibitor is definitely a welcome addition to our toolkit. There certainly are patients who have been hesitant to use PCSK9 inhibitors as injectable therapies, especially as self-administered subcutaneous injections. Enlicitide (Lipfendra) is what we're talking about as the first FDA-approved oral PCSK9 inhibitor, and I think it has an efficacy profile similar to other PCSK9 inhibitors and a favorable safety profile, so I go over those things with patients. We also talk about the fact that there are still trials ongoing with some of our PCSK9 inhibitors. Evolocumab and alirocumab have been around longer and have cardiovascular outcomes trials, and that includes recent data from VESALIUS-CV for evolocumab. Inclisiran (Leqvio) is in outcomes trials, and enlicitide is in outcomes trials. But at the end of the day, it again comes down to personalized decision-making. By the time you get toward the end of that conversation with the patient, you're getting a pretty clear sense of what's acceptable to them and what their preferences are, and you're putting all those things together and thinking through where this fits into their other treatment, their other medications, and their treatment target. What's it going to take to get there?

Sure. It's funny; one of the themes we've touched on here is personalization. Lipid management has become way more personal—not that it wasn't before, but given the breadth of things we have to choose from, the goals, how we're able to further risk stratify people, and then the different treatment options we can talk to patients about, even given their own regimen. I was having this conversation the other day with someone. I think there was also an article in The New York Times about people overcoming their fear of injections to take GLP-1 receptor agonists, for example. But then you think about PCSK9 inhibitors, and it feels like more and more injectable therapies are coming out. Are people going to be willing to accept 8 different types of injections? What is that going to look like if we're now so injection-heavy as a treatment for different disease states? Because there are other cardiovascular agents coming down the line that are injectables. So yes, you don't have to inject them every day—it's weekly or so—but it's still a lot of injectables.

I was going to say, actually, in patients who are already on a GLP-1 receptor agonist injection, one of the things about prescribing a monoclonal antibody is that it's only every other week instead of every week. Some patients I've seen are like, "Oh, okay, not every week, just every other week."

Right. But it's a little trade-off, right?

Yes, but I agree with you completely. We've always had to think through polypharmacy or multiple medications, especially ones that patients have to get insurance approval for that would otherwise have high out-of-pocket costs. I think we need to be really thoughtful in the way we recommend these medications, so patients are really getting the most benefit out of the ones we recommend.

Absolutely, and this actually brings us to the last clinical question. Of course, I'm biased because I'm a pharmacist. How are you using pharmacists in your clinic? Do you have pharmacists in your clinic, or are you working with pharmacists? How do you employ or engage with the pharmacy team?

We have pharmacists integrated into our cardiovascular clinic at UC San Diego, and they play a number of roles. They provide support to the entire clinic for things like medication refills and authorizations, and there are some groups within cardiology where pharmacists are even more integrated and are seeing patients, in our heart failure subspecialty group, for example. But I think that having pharmacists more and more integrated into our everyday care of patients is something we need to strive for. I would love to have even more support than we do. I think pharmacists can really help us optimize care delivery for patients. They can help us in these nuanced conversations about risks and benefits, monitoring adverse effects, making dose adjustments, and following up on efficacy with things like repeat lipid panels, so that we can stay within guideline recommendations for when to repeat labs and titrate medications. It's a huge contribution. And like you've said, in this era of an expanding toolkit in lipidology, having pharmacists involved in helping us get these new medicines to the right patients is a huge role that pharmacists can play.

Absolutely. Well, I appreciate that. The last question we have is a nonclinical one: Are there any good books, TV shows, or podcasts you've enjoyed in the last several months that you would recommend?

Oh, that's a good question. I read a book just recently, The Mysterious Case of Rudolf Diesel.

Okay.

Diesel is the inventor of the diesel engine.

Oh, yes.

His story is really interesting. It's all about his invention and trying to figure out how it was going to work its way into the fabric of society and do something good for humanity. Through things like World War I, and its adoption into machines used for war, the diesel engine didn't really work out the way he had hoped in terms of inventing something for the good of all humanity. It's an interesting story about—

—the narrative of what the hopes are vs how it is used.

How we invent things. When we invent things, how do we get them into society in the right way, and how are—

—they used. Yes, exactly. Interesting. Very good. Dr Michael Wilkinson, thank you so much for being here. This was outstanding. It's always good to hear the lens of our physicians and team leads who are doing this and how we work through it. I appreciate you being here, and I appreciate the NLA for letting us do this joint effort. And you're the incoming president—are you the president now of the NLA?

I'm on the executive council of the NLA.

Thank you. Very good. As always, like and subscribe if you like this content, and please let us know. We'll continue to produce and do different things. More to come on lipids. If I'm not mistaken, I think HORIZON is going to be presented at AHA.

I think that's what we're expecting, yes.

We will definitely have a follow-up to that. All right, thank you all. Please enjoy, and come back and hear us in a few weeks with a new episode. Thank you.