<p>The range of options available for lipid-lowering therapy provides the potential to improve the gap between guideline recommendations and real-world management, and it helps personalize treatment choices. Opportunities for individualized approaches to low-density lipoprotein cholesterol (LDL-C) management were presented at the <strong>American Heart Association (AHA) Scientific Sessions 2025</strong>.</p> <p><br></p> <p><em>Following these presentations, featured expert Seth Martin, MD, MHS, was interviewed by </em>Conference Reporter<em> Associate Editor-in-Chief Mona Shah, PharmD. Clinical perspectives from Dr Martin on these findings are presented here.</em></p>

We have a lot of opportunities to personalize hypercholesterolemia treatment because patients have different risk factor profiles in the primary and secondary prevention settings. We take these profiles into account, including patients’ LDL-C and lipoprotein(a) levels, coronary artery calcium scores, responses to prior therapies, and preferences for treatment.

<br>

With the breadth of available treatment options for hypercholesterolemia, including statins, ezetimibe, PCSK9 inhibitors, bempedoic acid, evinacumab, lomitapide, and even apheresis, there is a lot of opportunity to find the right management plan for individual patients. I view it very much as a partnership between the clinician and the patient to figure out what works best and fits their goals and preferences. We have come a long way in the last decade, and the more choices we have, the greater the need to develop a personalized approach.

<br>

In the primary prevention setting, for a patient with hypercholesterolemia who has never had a cardiovascular (CV) event, following the guidelines we can start to develop a treatment strategy based on existing clinical situations, such as familial hypercholesterolemia or severe hypercholesterolemia (ie, an LDL-C of ≥190 mg/dL), diabetes, or calculated 10-year risk of atherosclerotic CV disease (ASCVD). Many patients fall into the group in whom we should personalize treatment based on their 10-year ASCVD risk calculation, and we use this in the context of a patient-clinician discussion to decide if there could be value in additional testing to guide the treatment intensity and to establish personalized LDL-C goals. Currently, the guideline recommendations are based on the Pooled Cohort Equations, but the new AHA Predicting Risk of CVD EVENTs (PREVENT) equations have been published and are anticipated to be incorporated into the upcoming guidelines.

<br>

As Roger S. Blumenthal, MD, highlighted during his presentation at the recent AHA Scientific Sessions 2025, these PREVENT equations for calculating 10- and 30-year risk have gained a lot of attention as we have become familiar with their performance in advance of their adoption in AHA dyslipidemia treatment guidelines. Dr Blumenthal discussed important lines of evidence indicating the anticipated benefits from starting lipid-lowering treatment earlier in life, which is an important consideration because the data are clear: ASCVD risk is tied to the cumulative exposure to LDL-C. If treatment is started earlier in life, one gets many more years to reduce cumulative LDL-C exposure vs a later reactionary approach using a higher-intensity therapy for a shorter amount of time. Therefore, for a younger patient whose LDL-C level remains elevated despite lifestyle changes, we may need to consider lowering our threshold for the institution of drug therapy.

<br>

Another notable presentation from the AHA meeting was on the VESALIUS-CV trial by Erin A. Bohula May, MD, DPhil, and colleagues, an exciting study of the monoclonal antibody (mAb) evolocumab conducted in individuals without a history of myocardial infarction or stroke but with a high ASCVD risk. There were many patients in VESALIUS-CV with advanced atherosclerosis by imaging, and there was also a large population of patients with high-risk diabetes. The authors reported impressive results, with a significant 25% relative risk reduction in the triple primary end point of major adverse CV events, including coronary heart disease death, myocardial infarction, or ischemic stroke. Additionally, reductions in the risk of all-cause and cardiovascular mortality favored the evolocumab group. These are important results because of the population studied and because of the duration of the trial. Prior trials of mAbs were shorter in duration, while this trial was more than 4 years in duration, and I believe that this longer duration enabled a greater risk reduction. VESALIUS-CV was a very well-received trial, with applause in the audience when the primary results were presented in New Orleans. The trial opens up interesting questions about the spectrum of ASCVD risk (blurring the lines between primary and secondary prevention), the importance of intense LDL-C lowering, and the longer-term benefits and safety of PCSK9 inhibitors. This reinforces the need for more proactive approaches to developing a personalized treatment plan with patients that considers the addition of PCSK9 inhibitor therapy. There is a spectrum of ASCVD risk, and we may need to decrease our reliance on the dichotomy of primary and secondary prevention.

<br>

Finally, the results of an implementation-focused program were presented by Luc Djousse, MD, DSc, at the AHA Scientific Sessions 2025 that I want to call attention to because we need more implementation science in cardiology. We have a well-established and growing armamentarium of drugs that show benefit in clinical trials, but when it comes to translating these benefits into routine clinical practice, as a field we often fall short. With that in mind, I thought that the VALOR-QI program conducted by the Department of Veterans Affairs Health System was quite interesting. Its aim was to identify and address barriers to LDL-C management among more than 140,000 veterans with ASCVD. It was found that more than 78,000 veterans had LDL-C levels that were 70 mg/dL or higher at baseline, so these secondary prevention patients were not where they should have been in terms of LDL-C control. The study identified common well-known barriers, including staffing shortages, poor adherence to lipid-lowering therapy, clinical inertia, and insufficient patient and professional education around lipid management. These were addressed through a variety of methods, including a coaching program, multidisciplinary teams, and educational materials about lipid and lifestyle management. The interventions achieved a 15.9-mg/dL improvement in mean LDL-C from baseline, which is a somewhat modest—but nevertheless important—result. Adherence to lipid-lowering therapy also improved, as did the total number of patients who achieved an LDL-C of less than 70 mg/dL.

<br>

This study shows us that, by addressing common barriers to lipid management through collaborative effort, we are able to make progress. In the coming years, I expect that we will see a lot more of these implementation science studies testing new creative strategies that can be shared and scaled up in practice. I think that we are going to learn a lot about how best to implement all the evidence-based lipid-lowering therapies in an individualized manner in clinical practice to better lower ASCVD risk for our patients with hypercholesterolemia.