Going Beyond Statins to Help ASCVD Patients Reach Their LDL-C Goals

Sponsored by Novartis Pharmaceuticals Corporation. Jason Liu, MD, was not compensated for his contributions to this article.

As cardiologists, management of LDL-cholesterol remains a common and crucial goal. Elevated LDL-C is one of the most modifiable risk factors for atherosclerotic cardiovascular disease (ASCVD) we can address in our patients.¹

It’s also one of the areas I find most scientifically exciting, given the pace of innovation in recent years. Though unplanned, my postgraduate research in genetics and RNA-interference (RNAi) happily collided with my perception and utilization of some of the emerging therapies in cardiology. In particular, I see tremendous promise in RNAi-based therapies—and my fascination with this technology continues to shape my clinical approach today.

Progress in the development of nonstatin therapies has the ability to transform how we care for patients; the LDL-C goal post continues to shift lower as novel therapies may give us the potential to achieve even lower LDL-C. This is particularly true for our patients who have experienced a cardiovascular event. As is the case in all areas of medicine, the journey to and staying at goal is still complex and requires more than a one-size-fits-all approach. Novel LDL-C–lowering treatments are emerging rapidly in the cardiology field, and incorporating these therapies thoughtfully into my clinical practice has made a big difference in helping many of my patients reach and maintain their LDL-C goals.

Lowering LDL-C After a Cardiovascular Event Is Critical

Getting LDL-C to target levels is critical, yet some evidence suggests only about 20% of ASCVD patients have their statin regimen adjusted despite having an LDL-C level >70 mg/dL.^2,3,4 The 2025 ACC/AHA Joint Committee Clinical Practice Guidelines for the Management of Patients with Acute Coronary Syndromes state that it is reasonable in this population to further intensify lipid-lowering therapy if the LDL-C level is 55 to <70 mg/dL for patients after acute coronary syndromes (ACS).³ This trend to aim for lower LDL-C in certain patients is echoed in the 2026 ACC/AHA/AACVPR/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Dyslipidemia.⁵

While I’ve found that many patients are incredibly motivated to make changes after a CV event, achieving and retaining LDL-C goals can still be a challenge for some. Statins are, of course, foundational to LDL-C lowering, but they may not do the trick for every patient.³ Adherence to statins can be a struggle for some due to side effects, some of which are perceived, health literacy, and many other factors.⁶ As our cardiac patients often struggle with multiple comorbidities, polypharmacy and pill burden is an issue—asking a patient to add on just “one more thing” can be overwhelming. And while we all advocate for lifestyle changes, sticking with them can be inconsistent, and maintaining persistent LDL-C reduction is important. Even when adhering to their statins and making lifestyle changes, some of my patients are just not able to get their LDL-C level to where it needs to be.

From my perspective, it’s less about how we get to LDL-C targets and more about getting there—and staying there. For patients who still struggle to get to LDL-C goal, the recently released 2026 ACC/AHA Multisociety Clinical Practice Guideline on the Management of Dyslipidemia has returned to a rigorous treat-to-target approach, underscoring clear and actionable LDL-C thresholds based on precise risk stratification. The new guideline reinforces the need for earlier identification and more aggressive treatment for longer LDL-C reduction over time, with ongoing LDL-C testing every 6-12 months to assess efficacy and adherence. The guideline also emphasizes personalization of treatment and benefits of sustained effect through patient adherence.⁵

The Potential of Novel Therapies

The proprotein convertase subtilisin/kexin type 9 (PCSK9) class of inhibitors ultimately increases the expression of LDL receptors in the liver such that LDL-C can be more effectively cleared from the bloodstream.⁷ This class of medication has proven itself to be very effective in lowering LDL-C. But for patients who have been relying on oral medications, a twice monthly self-injection of a type of PCSK9 inhibitor that is a monoclonal antibody, sometimes requires a mental leap for those not comfortable with self-injecting at that frequency.

This is where I’ve found LEQVIO® (inclisiran), a PCSK9 inhibitor that is a small interfering RNA therapy, to be helpful for my patients who may need extra help lowering their LDL-C.⁸ LEQVIO is indicated as an adjunct to diet and exercise to reduce LDL-C in adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia (HeFH).⁸ What makes a big difference to my patients is that it is administered by a health care provider just twice a year, after two initial doses, which I’ve found really supports my patients’ ability to manage and remain consistent with a treatment plan.⁸ And in my experience, it’s well tolerated.

The mechanism of action of LEQVIO is fascinating to me, since it targets PCSK9 and engages the body’s natural process of RNA interference.⁸ It is molecularly designed to target the liver and is slowly released into the cytoplasm, which is partly responsible for the long-duration effect and loads the RNA-induced silencing complex (RISC) to sequentially cleave multiple copies of PCSK9 mRNA and prevent PCSK9 protein synthesis.^8,9,10 This results in LDL receptor expression to filter out circulating LDL-C.⁸

I was originally impressed by the pivotal data for LEQVIO (ORION-10 and ORION-11), which showed an LDL-C reduction of up to 52% for adults with hypercholesterolemia and ASCVD or an increased risk of ASCVD, including HeFH, at months 17 compared to placebo.¹¹

Importantly, for many of my patients, evidence from a trial—V-INCEPTION—in a real-world setting has shown that in patients who have had a coronary event, LEQVIO demonstrated a 47% LDL-C reduction difference from usual care alone at Day 330.¹² Additionally, 67% of patients receiving LEQVIO achieved an LDL-C target of <70 mg/dL compared with 28% of patients receiving usual care alone.¹²

One thing I find in the study is worth mentioning because it spotlights how patients may not always be treated according to ACC/AHA recommendations: in the “usual care” arm, which included statin and nonstatin LDL-C–lowering treatment as considered appropriate by the clinician, a majority of patients (68%) remained on statins only.¹³ The fact that a minority of patients received an additional nonstatin therapy to me suggests that HCPs are not using all the strategies available to them as recommended by ACC/AHA. This suggests that more concerted efforts are needed to nudge clinicians toward following the 2026 ACC/AHA Multisociety Clinical Practice Guideline on the Management of Dyslipidemia more closely.

I find these data very persuasive, and they mirror what I’ve seen in my own practice. My patients have been overwhelmingly open to adding LEQVIO to their routine, since they feel that its twice-yearly maintenance dosing, after two initial doses, can work well with their lifestyles and can be incorporated into regular office visits. No additional pills or self-injections. I believe this may have helped with the strong adherence I’ve seen among my patients.¹⁴

Shared Decision-Making Is the Name of the Game

In the era of the internet, and more recently, artificial intelligence, shared decision-making has become an essential part of routine practice. Patients today are more informed than ever: They do their own research, come prepared with questions, and almost always want to understand the decision-making process—as they should. As clinicians, the art of medicine in this modern era is as much about presenting evidence-based data as it is about guiding our patients towards choosing a treatment course that best accommodates their lifestyle and beliefs. A good therapeutic alliance is necessary to drive change.

Nonstatin treatments, like LEQVIO, have become regular additions to my practice, because they provide an additional therapeutic choice. Additionally, these treatments offer a lot of hope for patients with ASCVD who need more than traditional statin therapies can provide to lower LDL-C.

I’m thrilled to be part of this chapter of cardiovascular medicine—one where science, innovation, and patient-centered care converge. With these nonstatin therapies, we are better equipped than ever to help patients reach and maintain their LDL-C goals. I’m optimistic about what’s ahead—and excited to be part of a field that continues to evolve in ways that measurably benefit our patients’ health and well-being.

INDICATION

LEQVIO (inclisiran) injection is indicated as an adjunct to diet and exercise to reduce low-density lipoprotein cholesterol (LDL-C) in adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia (HeFH).

IMPORTANT SAFETY INFORMATION

Contraindication: 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 anaphylaxis and angioedema.

Hypersensitivity Reactions: Hypersensitivity reactions, including anaphylaxis and angioedema, have been reported in patients treated with LEQVIO. Advise patients on the signs and symptoms of hypersensitivity reactions and instruct patients to seek medical attention promptly.

Adverse Reactions: Adverse reactions in clinical trials (≥3% of adult patients treated with LEQVIO and more frequently than placebo) were injection site reaction, arthralgia, and bronchitis.

Please click here for accompanying LEQVIO full Prescribing Information.

References:

1. 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. doi:10.1093/eurheartj/ehx144
2. 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):533-543. doi:10.1161/CIRCOUTCOMES.122.009787
3. 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. Circulation. 2025;151(13):e771-e862. doi:10.1161/CIR.0000000000001309
4. Wong ND, Young D, Zhao Y, et al. Prevalence of the American College of Cardiology/American Heart Association statin eligibility groups, statin use, and low-density lipoprotein cholesterol control in US adults using the National Health and Nutrition Examination Survey 2011-2012. J Clin Lipidol. 2016;10(5):1109-1118. doi:10.1016/j.jacl.2016.06.011
5. Blumenthal RS, Morris PB, Gaudino M, et al. 2026 ACC/AHA/AACVPR/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Dyslipidemia: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. Published online March 13, 2026. doi:10.1016/j.jacc.2025.11.016
6. Turin A, Pandit J, Stone NJ. Statins and nonadherence: should we RELATE better? J Cardiovasc Pharmacol Ther. 2015;20(5):447-456.
7. PCSK9 Inhibitors. Cleveland Clinic. https://my.clevelandclinic.org/health/drugs/22550-pcsk9-inhibitors. Accessed August 4, 2025.
8. Leqvio. Prescribing information. Novartis Pharmaceuticals Corp.
9. Khvorova A. Oligonucleotide therapeutics—a new class of cholesterol-lowering drugs. N Engl J Med. 2017;376(1):4-7. doi:10.1056/NEJMp1614154
10. Fitzgerald K, White S, Borodovsky A, et al. A highly durable RNAi therapeutic inhibitor of PCSK9. N Engl J Med. 2017;3761(1):41-51. doi:10.1056/NEJMoa1609243
11. 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. doi:10.1056/NEJMoa1912387
12. Knowlton KU, Navar AM, Anderson JL, et al. LDL-C management with inclisiran plus usual care vs usual care alone in participants with recent acute coronary syndrome: VICTORION-INCEPTION. Presented at: National Lipid Association’s 2025 Annual Scientific Sessions; May 29-June 1, 2025; Miami, FL.
13. Data on file. Study NCT04873934. V-INCEPTION Core Squad Messaging Document. Novartis Pharmaceuticals Corp; 2025.
14. Niu X, Popadic L, Xinshuo M, 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.

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