Managing LDL-C Levels and Adherence to Lipid-Lowering Therapies After a Recent Coronary Event: Putting Data Into Practice

Transcript

ReachMD Announcer:
Welcome to ReachMD. This medical industry feature is titled Managing LDL-C Levels and Adherence to Lipid-Lowering Therapies After a Recent Coronary Event: Putting Data Into Practice.

Dr Drzymalski:
Hello, and welcome to today’s podcast. This program is sponsored by Novartis Pharmaceuticals Corporation and is intended for US health care professionals. We’ve been compensated by Novartis Pharmaceuticals Corporation for our time. I’m Dr Krzysztof Drzymalski, and I’m an interventional cardiologist at Capital Cardiology Associates in Albany, New York. I chose interventional cardiology as my profession because I love to be hands-on and fix a problem at its source. And what’s more important than the heart? It’s the body’s engine. I’m excited to be here today to discuss the importance of LDL-C management after a recent coronary event.

A coronary event is defined as an acute coronary syndrome, which includes unstable angina, ST-elevation myocardial infarction, non–ST elevation myocardial infarction, and/or coronary revascularization.¹

I am here today joined by Dr Iluyomade.

Dr Iluyomade:
Thank you, Dr Drzymalski! I’m Dr Adedapo Iluyomade, but most of my patients and colleagues call me Dr Dapo. I’m a preventive cardiologist at Miami Cardiac & Vascular Institute in Florida. I was first drawn to cardiology for its data-driven nature, but my interest in cardiology became personal after my father’s stroke. For me, this event solidified the importance of learning more about cardiovascular disease prevention and ensuring aggressive LDL-C management. This led me to the evolving field of preventive cardiology, which focuses on managing risk factors. Dr Drzymalski, as you mentioned, a discussion on LDL-C management is crucial because only a small number of patients who are considered high risk actually achieve target LDL-C levels after a coronary event, despite strong evidence and guidelines supporting the need for LDL-C reduction.^2,3

Dr Drzymalski:
Yes, I agree LDL-C management is such an important point to emphasize. In today’s podcast, we will share our clinical experiences and perspectives regarding the importance of LDL-C management in patients who have had a recent coronary event. We will also highlight key data that demonstrate how LEQVIO^® (inclisiran) may be an option for managing elevated LDL-C levels in patients who still remain above goal while on statin therapy. Before we begin, let’s go over the indication for LEQVIO.

INDICATION
LEQVIO^® (inclisiran) injection is indicated as an adjunct to diet and statin therapy for the treatment of adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia, or HeFH, to reduce low-density lipoprotein cholesterol, or LDL-C.⁵

So, let’s get started. Dr Dapo, can you tell us why it’s important to focus on LDL-C management, especially for patients after a coronary event?

Dr Iluyomade:
Absolutely! Multiple studies have shown that LDL-C is one of the most modifiable risk factors for atherosclerotic cardiovascular disease, or ASCVD, and therefore, immediate action is needed to reduce LDL-C levels in patients after a recent coronary event.^5-8 However, in an analysis of data from the Family Heart Database, patients who achieve their target LDL-C levels are only able to maintain those levels for less than 6 months on average.² Nonadherence to lipid-lowering therapies may be preventing patients from getting to and maintaining their LDL-C target. After a coronary event, I believe patients need to make adherence to a lipid-lowering therapy a priority.^9,10

With that said, how do you prioritize LDL-C management in your patients who have had a recent coronary event?

Dr Drzymalski:
In my experience, for many patients who’ve had a recent coronary event, they can expect to begin on some type of intervention—presumably, diet and initiation of a high-intensity statin. Yet over time, some of these patients stop taking their medications, and as clinicians, we notice this when they come back for their follow-up appointments.

I find that many patients have not had their LDL-C levels checked at the time of their coronary event. In my practice, we prioritize LDL-C management by ensuring all patients have their lipid panel checked at the time of the event. When patients are prescribed LEQVIO, we have an automatic system to obtain regular lipid panels to trend at future appointments.

Dr Iluyomade:
I really like that approach, Dr Drzymalski. How do you communicate the importance of prioriizing LDL-C management to your peers?

Dr Drzymalski:
I have conversations with the cardiologists in my pracice to ensure the patient’s LDL-C level remains a top priority. Published data indicate that up to 80% of patients with ASCVD do not reach the guideline-recommended LDL-C target of less than 70 mg/dL.¹¹

And from my experience, this doesn’t surprise me. But I believe it’s important for us to overcome this clinical inertia and take further action for our patients by prescribing additional lipid-lowering therapies beyond statins, when appropriate.^8,12 I remind my colleagues that each patient may have a different level of risk for a coronary event based on muliple factors, such as family history and comorbidities, but the goal should always be to lower their LDL-C levels.¹ I like to think of LDL-C management as being on a highway. It is recommended to drive within the speed limit. LDL-C management is similar. It’s best to get your level within the recommended guidelines.^3,7 Please note that the effect of LEQVIO on cardiovascular morbidity and mortality has not been determined.

So, Dr Dapo, if I were to refer my patient with a post-coronary event to you, what would the conversation look like from your perspective when transitioning the patient's care? What would be your next step in ensuring that patients continue to stay on lipid-lowering treatments?

Dr Iluyomade:
Well, the conversation that I have with interventional cardiologists is usually brief but essential—covering key details about the type of event, any related complicaions, any prior medications that the patient may have been taking, including any lipid-lowering treatments. I then take lead on tracking follow-up care. I tell the patient that staying on lipid-lowering treatment is essential—when we stop treatment, the LDL-C level will rise again.⁷ In my clinical experience, many patients find it tough to stick with their lipid-lowering medicaions. Sometimes, they are just overwhelmed by multiple medications. There are also concerns about side effects.^9,10 Some worry that their cholesterol might be “too low,” leading them to adjust the dose on their own, but it’s important to clarify that when it comes to LDL-C levels, lower is better.⁷

Dr Drzymalski:
Without a doubt, Dr Dapo, emphasizing the importance of adherence to lipid-lowering therapies is a key priority for me when managing LDL-C in post-event patients. Despite a therapy’s proven effectiveness, its success depends on whether it’s actually being taken as prescribed. With that in mind, I often consider LEQVIO for my patients after a coronary event if their statin is not getting their LDL-C where I want it to be. Clinical trial results for LEQVIO demonstrate proven efficacy and a well-tolerated safety profile.⁴

Due to the clinical profile, I consider LEQVIO as a treatment option that may help patients achieve their LDL-C target.⁴ In fact, in 2025, the ACC/AHA Joint Commiree published updated clinical practice guidelines for the management of patients with acute coronary syndromes.³ The guideline states that the addition of non-statin lipid-lowering agent is recommended for patients already on maximally tolerated statin who have an LDL-C greater than or equal to 70 mg/dL.³ This is categorized as a class 1 strong recommendaion and emphasizes the need to include a non-statin lipid-lowering therapy, which includes LEQVIO, along with maximally tolerated statins for LDL-C management.^3,13

The guideline also states that the addition of a non-statin lipid-lowering agent is reasonable for patients with a lower LDL-C, between 55 and 69mg/dL, already on a maximally tolerated statin.³ This is categorized as a class 2a recommendation and suggests a more aggressive approach in this patient population.^3,13 I’m excited to see the inclusion of non-statin lipid-lowering therapies, including LEQVIO, in the guidelines.³ This additional step is exactly what we should be doing for our patients after a coronary event when appropriate. Dr Dapo, what are your thoughts on these 2025 guidelines?

Dr Iluyomade:
From my experience, in most cases, a non-statin lipid-lowering therapy is needed in addition to statins to get patients who have experienced a recent coronary event below LDL-C levels of 70 mg/dL. I think the 2025 guidelines will give cardiologists more confidence to add a non-statin lipid-lowering therapy, which includes LEQVIO, for their patients when necessary.

The guideline also provides recommendations, including reassessment of lipid levels post discharge.³ A fasing lipid panel is recommended 4 to 8 weeks after initiating or adjusing the dose of lipid-lowering therapy to assess response or adherence to therapy.³ I’ve noticed many patients do not have a lipid panel drawn within a year after their coronary event, so these guidelines may encourage cardiologists to run these tests earlier and more frequently.

Dr Drzymalski::
So, Dr Dapo, when talking to your colleagues, how would you communicate the key attributes of LEQVIO?

Dr Iluyomade:
Well, I begin by explaining how LEQVIO is a first-in-class, small interfering RNA therapy that targets the liver by using the body’s natural RNA interference process.^4,14

Dr Drzymalski, can you walk us through some of the key clinical data for LEQVIO?

Dr Drzymalski:
Certainly. LEQVIO was studied in two Phase 3, multicenter, double-blind, randomized, placebo-controlled, 18-month trials, ORION-10 and ORION-11.^4,15 ORION-10 enrolled patients who had ASCVD. ORION-11 also enrolled patients with ASCVD and included patients with increased risk of ASCVD.⁴ Factors that increased risk of ASCVD included heterozygous familial hypercholesterolemia or FH, type 2 diabetes mellitus, or 10-year risk scores of greater than or equal to 20%.¹⁵ All patients were receiving maximally tolerated statin therapy with or without ezetimibe and required additional LDL-C lowering.^4,15

In the ORION-10 study, LEQVIO demonstrated powerful and consistent LDL-C reduction throughout each 6-month dosing interval, with a 52% LDL-C reduction difference from placebo at Month 17.⁴ Also, 84% of patients treated with LEQVIO achieved guideline-recommended LDL-C targets of lower than 70 mg/dL at Month 17, compared with 18% of placebo-treated patients.¹⁶ These results were similar in the ORION-11 study.¹⁵

The 2022 ACC Expert Consensus Decision Pathway recommends an LDL-C goal of less than 55 mg/dL for patients with ASCVD at very high risk, and suggests adding a non-statin therapy if LDL-C remains greater than or equal to 55 mg/dL.¹⁷ Given this, let’s review how many patients from the LEQVIO pivotal trials reached this target. In ORION-10, 75% of patients receiving LEQVIO achieved an LDL-C less than 55 mg/dL compared with 4% of patients on placebo at Month 17.¹⁸ Results were similar in patients with ASCVD in the ORION-11 trial.¹⁹
Additionally, these results from the pivotal trials for LEQVIO are, in fact, consistent with what I see in my clinic. Dr Dapo, besides discussing the efficacy of LEQVIO, what other aspects do you consider important to emphasize?

Dr Iluyomade:
That’s a great question. When I meet a patient following their coronary event, I focus on the fact that LEQVIO offers proven efficacy with a well-tolerated safety profile.⁴ While discussing the safety profile of LEQVIO, I tell my patients that side effects with LEQVIO have been well-tolerated, and they find that reassuring.⁴ I explain to them that, based on Phase 3 clinical trials over 18 months, the most common adverse reactions occurring in greater than or equal to 3% of patients treated with LEQVIO, and more frequently than placebo, were injection site reaction, arthralgia, and bronchitis.^4,15

And adverse reactions leading to discontinuaion occurred in 2.5% of patients treated with LEQVIO versus 1.9% of patients receiving placebo.⁴ It’s important to note that injection site reactions were the most common causes for treatment discontinuaion observed in 0.2% of patients taking LEQVIO versus 0% taking placebo.⁴ And the majority of adverse events were mild to moderate.²⁰

Dr Drzymalski:
Thank you for that recap of the LEQVIO safety data. Can you share what this discussion looks like for patients who are prescribed LEQVIO, based on the real-world evidence on adherence?

Dr Iluyomade:
Of course. In our practice, keeping patients on track with their LDL-C–lowering therapy is a top priority. We support our patients every step of the way—through face-to-face discussions and printed educational materials. We have a nurse navigator who helps patients keep up with appointments, medications, and necessary lab work, including lipid panels. That’s where LEQVIO makes a real difference. Only LEQVIO is HCP-administered, so once it’s given, you know that the patient received their dose. One dose of LEQVIO is administered initially, again at 3 months, and then every 6 months.^4,21-24 Once administered, there’s no chance of a missed dose for 6 months.⁴ Just 2 injections a year after the 2 initial doses instead of frequent injections.⁴ That's something many of my patients prefer. And we now have adherence data to show that patients are staying on LEQVIO.

Real-world data are available from a retrospective, observational, real-world study evaluating 12-month adherence and persistence for newly initiated patients on LEQVIO, evolocumab, and alirocumab using data from an administraive claims database.²⁵ The LEQVIO, evolocumab, and alirocumab groups included over 800, 27,000, and 8000 patients, respecively.²⁵ 79% of patients receiving LEQVIO were fully adherent at 12 months versus 56% for either evolocumab or alirocumab, where adherence was defined as the proportion of days covered, or PDC.²⁵ Fully adherent patients were defined as having a PDC of greater than or equal to 0.825.

In addition, 80% of patients were persistent on LEQVIO for 12 months versus approximately 57% on either evolocumab or alirocumab.²⁵ Persistence was defined as patients on therapy for 12 months after the index date, with less than or equal to 90 days’ gap for LEQVIO, and less than or equal to 60 days’ gap for evolocumab and alirocumab between the last day of days’ supply and start of the next prescription.²⁵ However, note that the comparison pertains only to differences in adherence or persistence as defined by this analysis and should not be considered a comparison of efficacy or safety.

Given that this is an observational real-world study, there are some limitations.²⁵ This study was conducted using administrative claims data, meaning it was collected for nonresearch purposes, with limited details on clinical variables and susceptibility to missing data and coding-related errors.²⁵ I’ll also note that since LEQVIO is HCP-administered, the claims ensure patients received the injection, whereas evolocumab and alirocumab claims do not confirm self-administration, thus PDC for PCSK9 monoclonal antibodies may be overestimated.^4,25 Dr Drzymalski, what does the real-world evidence on adherence to LEQVIO mean for you and your patients? How do you ensure that adherence and persistence stay top of mind in your practice?

Dr Drzymalski:
I think adherence is underappreciated since we only see our patients twice a year. You can’t be certain if a patient is compliant with their therapy unless you are regularly monitoring their lipid levels. To me, a patient receiving a LEQVIO injection on the same day as their cardiology visit makes the most sense as it ensures the patient is getting their dose.

That brings us to the close of today’s program. Dr Dapo, thank you for the discussion today.

Dr Iluyomade:
And thanks for listening. For more information about LEQVIO, please visit LEQVIOHCP.com/expert-perspectives.

Important Safety Information. LEQVIO is contraindicated in patients with a prior serious hypersensitivity reaction to inclisiran or any of the excipients in LEQVIO. Serious hypersensitivity reactions have included angioedema. Adverse reactions in clinical trials, greater than or equal to 3% of patients treated with LEQVIO and more frequently than placebo, were injection site reaction, arthralgia, and bronchitis. Please see full LEQVIO Prescribing Information on this site or at LEQVIOHCP.com. Important Safety Information for LEQVIO is available underneath the player of this audio presentation.

ReachMD Announcer:
This program was sponsored by Novartis Pharmaceuticals Corporation. If you missed any part of this discussion, visit ReachMD.com/IndustryFeature. This is ReachMD. Be Part of the Knowledge.

References:

1. Singh A, Museedi AS, Grossman SA. Acute Coronary Syndrome. In: StatPearls. Treasure Island (FL): StatPearls Publishing; July 10, 2023.
2. Prioritizing LDL-cholesterol control. Family Heart Foundation. Published October 26, 2023. Accessed May 15, 2025. https://familyheart.org/wpcontent/uploads/2023/10/FamilyHeartFoundation_LDLPolicyStatement_Pages_20231026.pdf
3. Prioritizing LDL-cholesterol control. Family Heart Foundation. Published October 26, 2023. Accessed July 9, 2024. https://familyheart.org/prioritizing-ldl-cholesterol-control
4. Rao SV, O'Donoghue ML, Ruel M, et al. 2025 ACC/AHA/ACEP/NAEMSP/SCAI guideline for the management of patients with acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines [erratum published in Circulation. 2025;151(13):e865. doi:10.1161/CIR.0000000000001328]. Circulation. 2025;151(13):e771-e862. doi:10.1161/CIR.0000000000001309
5. Leqvio. Prescribing information. Novartis Pharmaceuticals Corp.
6. Fox KM, Tai M-H, Kostev K, et al. Treatment patterns and low-density lipoprotein cholesterol (LDL-C) goal attainment among patients receiving high- or moderate-intensity statins. Clin Res Cardiol. 2018;107(5):380-388.
7. Underberg J, Toth PP, Rodriguez F. LDL-C target attainment in secondary prevention of ASCVD in the United States: barriers, consequences of nonachievement, and strategies to reach goals. Postgrad Med. 2022;134(8):752-762.
8. Ference BA, Ginsberg HN, Graham I, et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J. 2017;38(32):2459-2472.
9. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;139(25):e1082-e1143.
10. Ingersgaard MV, Helms Andersen T, Norgaard O, Grabowski D, Olesen K. Reasons for nonadherence to statins – a systematic review of reviews. Patient Prefer Adherence. 2020;14:675-691.
11. Bradley CK, Shrader P, Sanchez RJ, Peterson ED, Navar AM. The patient journey with proprotein convertase subtilisin/kexin type 9 inhibitors in community practice. J Clin Lipidol. 2019;13(5):725-734.
12. Navar AM, Kolkailah AA, Gupta A, et al. Gaps in guideline-based lipid-lowering therapy for secondary prevention in the United States: a retrospective cohort study of 322 153 patients. Circ Cardiovasc Qual Outcomes. 2023;16(8)(suppl):533-543.
13. Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020;41(1):111-188. 
14. Kumbhani DJ, Cibotti-Sun M, Moore MM. 2025 acute coronary syndromes guideline-at-aglance. J Am Coll Cardiol. Published online February 27, 2025. doi:10.1016/j.jacc.2025.01.018
15. Khvorova A. Oligonucleotide therapeutics — a new class of cholesterol-lowering drugs. N Engl J Med. 2017;376(1):4-7.
16. Ray KK, Wright RS, Kallend D, et al. Two phase 3 trials of inclisiran in patients with elevated LDL cholesterol. N Engl J Med. 2020;382(16):1507-1519.
17. Ray KK, Wright RS, Kallend D, et al. Two phase 3 trials of inclisiran in patients with elevated LDL cholesterol. N Engl J Med. 2020;382(16)(suppl):1507-1519.
18. Writing Committee; Lloyd-Jones DM, Morris PB, Ballantyne CM, et al. 2022 ACC expert consensus decision pathway on the role of nonstatin therapies for LDL-cholesterol lowering in the management of atherosclerotic cardiovascular disease risk: a report of the American College of Cardiology Solution Set Oversight Committee [erratum published in J Am Coll Cardiol. 2023;81(1):104. doi:10.1016/j.jacc.2022.11.016]. J Am Coll Cardiol. 2022;80(14):1366-1418.
19. Data on file. ORION-10. Novartis Pharmaceuticals Corp; 2025.
20. Data on file. ORION-11. Novartis Pharmaceuticals Corp; 2025.
21. Wright RS, Ray KK, Raal FJ, et al. Pooled patient-level analysis of inclisiran trials in patients with familial hypercholesterolemia or atherosclerosis. J Am Coll Cardiol. 2021;77(9):1182-1193.
22. Repatha. Prescribing information. Amgen Inc.
23. Praluent. Prescribing information. Regeneron Pharmaceuticals, Inc.
24. Nexlizet. Prescribing information. Esperion Therapeutics, Inc.
25. Nexletol. Prescribing information. Esperion Therapeutics, Inc.
26. Niu X, Popadic L, Ma X, et al. Treatment patterns among early inclisiran vs anti-PCSK9 mAbs users: a retrospective analysis of US claims databases. Poster presented at National Lipid Association Scientific Sessions 2024; May 30-June 2, 2024; Las Vegas, NV. Poster 158.

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