News|Articles|June 24, 2026
The Risk of Waiting: The Case for Lower LDL-C – Earlier in the Atherosclerotic Disease Continuum
Author(s)Sponsored by Amgen
New data suggest that intensive LDL-C lowering may reduce CV risk in multiple high-risk patient profiles
For decades, intensive low-density lipoprotein cholesterol (LDL-C)‑lowering strategies have largely focused on patients with established cardiovascular disease (CVD)1 — but recent evidence demonstrates the benefits of meaningfully reducing LDL-C before a CV event takes place.
Worrisome Trends in Cardiovascular Disease
In the U.S., a heart attack occurs approximately every 40 seconds, and nearly 75% of these are first-time events.2 Despite advances in CVD care, overall event rates remain unacceptably high, with little improvement over the past decade.3 For many patients, this first heart attack is not spontaneous, but rather reflects years of cumulative, silent risk4,5 – representing missed opportunities for identification and intervention earlier in the atherosclerotic disease process.
New Clinical Data Demonstrate Impact of LDL-C Lowering in High-Risk Patients
In routine practice, many clinicians have historically waited until atherosclerosis develops or a CV event occurs before intensifying lipid-lowering therapy, even though LDL-C is one of the most modifiable risk factors to help reduce the risk of a heart attack.6 Outcomes data from the Phase 3 VESALIUS-CV trial of
INDICATION
Repatha® is indicated:
- To reduce the risk of major adverse cardiovascular (CV) events (CV death, myocardial infarction, stroke, unstable angina requiring hospitalization, or coronary revascularization) in adults at increased risk for these events.
IMPORTANT SAFETY INFORMATION
- Contraindication: Repatha® is contraindicated in patients with a history of a serious hypersensitivity reaction to evolocumab or any of the excipients in Repatha®. Serious hypersensitivity reactions including angioedema have occurred in patients treated with Repatha®.
Please see additional Important Safety Information later in this article.
The VESALIUS-CV trial evaluated more than 12,000 patients at high CV risk without prior history of heart attack or stroke.7 Results published in the New England Journal of Medicine showed that Repatha significantly reduced the risk of the dual primary composite endpoints: time to first occurrence of myocardial infarction (MI), ischemic stroke, and coronary heart disease (CHD) death (3-Point major adverse cardiovascular event [MACE]) by 25%; and time to first occurrence of 3-Point MACE plus any ischemia-driven arterial revascularization (4-Point MACE) by 19%.7 Repatha also significantly reduced the risk of a first heart attack by 36%.7 In a lipid sub-study, adding Repatha to a maximally tolerated dose of statin and/or ezetimibe resulted in substantially lower LDL-C levels among observed patients, with a median level of 45 mg/dL compared to 109 mg/dL in the placebo group.7
Now, building on the primary trial results, new data from prespecified exploratory subanalyses suggest positive outcomes in specific high-risk populations.
At the 2026 American College of Cardiology (ACC) Scientific Sessions,
Across both prespecified exploratory subanalyses, the median LDL-C achieved with Repatha added to optimized LDL-C-lowering therapy was ~45 mg/dL.8,9
“Patients shouldn’t have to experience a heart attack, stroke, or advanced atherosclerosis before we act,” said Sirisha Vadali, MD, board-certified non-invasive cardiologist and advanced lipidologist with Honor Health. “The data is clear: More intensive LDL-C lowering reduces the risk of major CV events. Prolonged exposure to high LDL-C increases that risk over time. It’s up to us as clinicians to act with greater urgency, to help high-risk primary prevention patients lower their LDL-C sooner - before a first MI or stroke.”
Patients with elevated LDL-C who previously had a heart attack or stroke have long been treated with Repatha to dramatically lower LDL-C and reduce the risk of another event.10,11 These subgroup analyses provide important insight into the benefits of LDL-C reduction earlier in the disease continuum.
Evolving Clinical Guidelines Support Earlier Intervention
The latest
For the first time in eight years, the Guideline re-introduces LDL-C goals and recognizes the importance of earlier, more intensive LDL-C lowering to reduce CV risk. For adults aged 40-75 with diabetes and multiple atherosclerotic CVD risk factors, LDL-C should be <70 mg/dL.12,13 In an accompanying
The Guideline also removes ezetimibe as a prerequisite to PCSK9 inhibitor use in many treatment pathways, enabling earlier use of monoclonal antibodies in select patient populations.13 Repatha is the only PCSK9 inhibitor proven to significantly reduce the risk of CV events in both high-risk primary and secondary prevention patients.7,10
The updated Guideline reflects broad clinical evidence showing that cumulative exposure to elevated LDL-C drives greater CV risk, underscoring that clinicians should not wait to act on this key driver of risk.
Primary care physicians (PCPs) are uniquely positioned to take decisive action, including for their patients with high LDL-C who are at risk for CVD. If PCPs initiate lipid-lowering therapy earlier in the atherosclerosis timeline, the impact could be significant, reducing the risk of experiencing a first CV event.
“When caring for a patient who has experienced a heart attack, I often think of what could have been done differently before the event,” said Vadali. “Collectively, the medical community is recognizing the power of earlier and more intensive intervention: treating at-risk patients sooner and getting their LDL-C below guideline-recommended levels. Physicians across the healthcare system, PCPs and cardiologists alike, must work together to ensure our patients receive the treatment they need, before their disease progresses.”
Translating Data to Clinical Impact with Repatha
Turning this data and the updated Dyslipidemia Guideline into impact only happens if patients are able to access and adhere to the medicines clinicians recommend. Since its approval over 10 years ago, Repatha has been prescribed to more than 9 million people worldwide,* and can be taken at home, at work, or on the go.15,16,17,† In a trial where patients were taught how to self-inject by a healthcare provider, 94% of patients successfully self-administered at home with the Repatha SureClick® device (prefilled single-dose [autoinjector]).18
Access for Repatha also continues to broaden, and it is now the most covered PCSK9 inhibitor monoclonal antibody in the U.S.,‡ with 96%§ of patients covered across insurance types, and most patients paying less than $50/month.19,20,** Repatha is also available through AmgenNow™, a program that makes certain Amgen medicines available directly to patients at a discounted monthly price. This program may benefit patients who are uninsured, have a high-deductible health plan, or prefer to pay out of pocket.
To learn more about Repatha data, visit
About the VESALIUS-CV Trial
VESALIUS-CV is a Phase 3, double-blind, randomized, placebo-controlled, global clinical trial designed to evaluate the impact of LDL-C lowering with Repatha (evolocumab) on MACE in adults at high CV risk with known ASCVD or high-risk diabetes without prior heart attack or stroke.7
VESALIUS-CV enrolled more than 12,000 patients with known ASCVD (CAD, atherosclerotic cerebrovascular disease, PAD) and/or high-risk diabetes (defined as diabetes that is long-standing [≥10 years], complicated by microvascular disease, or daily insulin use), who had no history of heart attack or stroke.7 All patients had at least 1 additional high-risk criterion; an LDL-C ≥ 90 mg/dL, or non-high-density lipoprotein cholesterol (non-HDL-C) ≥ 120 mg/dL, or apolipoprotein B ≥ 80 mg/dL; and treated with highest tolerated dose of statin and/or ezetimibe.7 The median baseline LDL-C was 122 mg/dL (IQR, 104-149 mg/dL) on local lab testing.7 Participants were randomized to receive Repatha or placebo in addition to optimized lipid-lowering therapy and were followed for a median of approximately 4.6 years.7
In the trial, Repatha significantly reduced the risk of major adverse cardiovascular events (MACE), including time to first occurrence of myocardial infarction (MI), ischemic stroke, and coronary heart disease (CHD) death by 25% (95% CI, 0.65-0.86; ARR 1.8%) and by 19% in a broader composite that also included any ischemia-driven arterial revascularization (95% CI, 0.73-0.89; ARR 2.8%).7 Repatha also significantly reduced the risk of a first MI by 36% (95% CI 0.52-0.79).7 In a lipid sub-study where all patients were on a background maximally tolerated dose of statin and/or ezetimibe, treatment with Repatha resulted in a median LDL-C level of 45 mg/dL compared to 109 mg/dL in the placebo group at week 48 (baseline LDL-C in the sub-study was 115 mg/dL).7
Prespecified Exploratory Subanalysis Presented at ACC
Data from a prespecified exploratory subanalysis of 3,655 adults without known significant atherosclerosis and with diabetes showed that adding Repatha to statins or other LDL-C-lowering therapy reduced the risk of MACE, including time to first occurrence of MI, ischemic stroke, or CHD death (3-point MACE) by 31% (95% CI, 0.52-0.91; ARR 2.1%) and 4-point MACE including 3-point MACE components + any ischemia-driven arterial revascularization by 31% (95% CI, 0.55-0.86; ARR 2.9%).8
Prespecified Exploratory Subanalysis Presented at ADA
Data from a prespecified exploratory subanalysis of 6,002 patients with high-risk diabetes (microvascular disease, insulin use or diabetic duration ≥10 years) and elevated LDL-C without prior heart attack or stroke showed that adding Repatha to statins or other LDL-C-lowering therapy reduced the risk of time to first occurrence of CHD death, MI or ischemic stroke by 29% (95% CI 0.59-0.86) and reduced the risk of a second composite endpoint that also included ischemia-driven revascularization, by 21% (95% CI 0.69-0.91).9
These subanalyses are considered exploratory, and no statistical conclusions can be drawn.
Footnotes
*Cumulative post-market exposure estimates from July 2015 through February 2026, on patients that have received at least 1 dose (estimates assume administration) of the product, which was estimated using prescription claims data (IQVIA) for the U.S. and units distributed (Amgen Finance Electronic Data Warehouse) with average drug utilization patterns (MarketScan claims data) for all other regions. Utilization assumptions were applied to calculate the unique number of patients.
†Make room in the refrigerator (36°F to 46°F) to store Repatha®. Storing Repatha® in its original carton protects the medicine from light. Before injecting Repatha®, you’ll need to take the device out of the refrigerator and let it sit to warm up to room temperature (30 minutes for Sureclick® Autoinjector and Prefilled Syringe). Repatha® can also be stored at room temperature at 68°F to 77°F (20°C to 25°C) for up to 30 days.
‡Includes commercial, health exchange, Medicaid, and Medicare lives, as of 2/2/2026, based on MMIT data. Inclusion on formulary does not imply superior clinical efficacy or safety. This information is subject to change without notice.
§Includes commercial, health exchange, Medicaid, and Medicare lives, as of February 2026, based on MMIT data. Inclusion on formulary does not imply superior clinical efficacy or safety. This information is subject to change without notice. For the most up-to-date and complete information regarding coverage of Repatha, please contact the relevant payer directly. Individual insurance requirements may vary.
**Based on IQVIA claims data from 1/1/2025 to 12/31/2025 using Commercial, Medicare, and Medicaid data. Patient out of pocket costs and insurance requirements may vary.
INDICATIONS
Repatha® is indicated:
• To reduce the risk of major adverse cardiovascular (CV) events (CV death, myocardial infarction, stroke, unstable angina requiring hospitalization, orcoronary revascularization) in adults at increased risk for these events.
• As an adjunct to diet and exercise to reduce low-density lipoprotein cholesterol (LDL-C) in adults with hypercholesterolemia and in adults with heterozygous familial hypercholesterolemia (HeFH)
IMPORTANT SAFETY INFORMATION
• Contraindication: Repatha® is contraindicated in patients with a history of a serious hypersensitivity reaction to evolocumab or any of the excipients in Repatha®. Serious hypersensitivity reactions including angioedema have occurred in patients treated with Repatha®.
• Hypersensitivity Reactions: Hypersensitivity reactions, including angioedema, have been reported in patients treated with Repatha®. If signs or symptoms of serious hypersensitivity reactions occur, discontinue treatment with Repatha®, treat according to the standard of care, and monitor until signs and symptoms resolve.
• Adverse Reactions in Primary Hypercholesterolemia: The most common adverse reactions (>5% of patients treated with Repatha® and more frequently than placebo) were: nasopharyngitis, upper respiratory tract infection, influenza, back pain, and injection site reactions.
From a pool of the 52-week trial and seven 12-week trials: Local injection site reactions occurred in 3.2% and 3.0% of Repatha®-treated and placebo-treated patients, respectively. The most common injection site reactions were erythema, pain, and bruising. Hypersensitivity reactions occurred in 5.1% and 4.7% of Repatha®-treated and placebo-treated patients, respectively. The most common hypersensitivity reactions were rash (1.0% versus 0.5% for Repatha® and placebo, respectively), eczema (0.4% versus 0.2%), erythema (0.4% versus 0.2%), and urticaria (0.4% versus 0.1%).
• Adverse Reactions in the FOURIER Cardiovascular Outcomes Trial: The most common adverse reactions (>5% of patients treated with Repatha® and more frequently than placebo) were: diabetes mellitus (8.8% Repatha®, 8.2% placebo), nasopharyngitis (7.8% Repatha®, 7.4% placebo), and upper respiratory tract infection (5.1% Repatha®, 4.8% placebo).
Among the 16,676 patients without diabetes mellitus at baseline, the incidence of new-onset diabetes mellitus during the trial was 8.1% in patients treated with Repatha® compared with 7.7% in patients that received placebo.
• Immunogenicity: Repatha® is a human monoclonal antibody. As with all therapeutic proteins, there is potential for immunogenicity with Repatha®.
Please
References
1 Cholesterol Treatment Trialists’ (CTT) Collaboration. (2010). Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170 000 participants in 26 randomised trials. The Lancet, 376(9753), 1670–1681. https://doi.org/10.1016/S0140-6736(10)61350-5
2 Martin, S. S., Blaha, M. J., Blankstein, R., Agatston, A., Rivera, J. J., Virani, S. S., Ouyang, P., Jones, S. R., Blumenthal, R. S., Budoff, M. J., & Nasir, K. (2014). Dyslipidemia, coronary artery calcium, and incident atherosclerotic cardiovascular disease: Implications for statin therapy from the Multi-Ethnic Study of Atherosclerosis. Circulation, 129(1), 77–86. https://doi.org/10.1161/CIRCULATIONAHA.113.003625
3 Woodruff, R. C., Tong, X., Khan, S. S., et al. (2023). Trends in cardiovascular disease mortality rates and excess deaths, 2010–2022. American Journal of Preventive Medicine, 66(4), 582–589.
4 Domanski, M. J., Tian, X., Wu, C. O., Reis, J. P., Dey, A. K., Gu, Y., Zhao, L., Bae, S., Liu, K., Hasan, A. A., Zimrin, D., Farkouh, M. E., Hong, C. C., Lloyd-Jones, D. M., & Fuster, V. (2020). Time course of LDL cholesterol exposure and cardiovascular disease event risk. Journal of the American College of Cardiology, 76(13), 1507–1516.
5 British Heart Foundation. (2026, January 16). High cholesterol: Symptoms, causes and levels. British Heart Foundation.
6 Yusuf, S., Hawken, S., Ôunpuu, S., Dans, T., Avezum, A., Lanas, F., McQueen, M., Budaj, A., Pais, P., Varigos, J., & Lisheng, L. (2004). Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): Case-control study. The Lancet, 364(9438), 937–952.
7 Bohula, E. A., Marston, N. A., Bhatia, A. K., De Ferrari, G. M., Leiter, L. A., Nicolau, J. C., Park, J.-G., Kuder, J. F., Murphy, S. A., Walsh, E., Wang, H., Blaha, V., Budaj, A., Cornel, J. H., Goudev, A., Kiss, R. G., Lorenzatti, A. J., Parkhomenko, A., Cyrille, M., … Sabatine, M. S. (2025). Evolocumab in patients without a previous myocardial infarction or stroke. The New England Journal of Medicine.
8 Marston, N. A., Bohula, E. A., Bhatia, A. K., et al. (2026). Evolocumab to reduce first major cardiovascular events in patients without known significant atherosclerosis and with diabetes: Results from the VESALIUS‑CV trial. JAMA.
9 Leiter, L. A., Giugliano, R. P., Marston, N. A., De Ferrari, G., Nicolau, J. C., Bhatia, A. K., et al. (2026). Evolocumab in patients with high-risk diabetes: Results from the VESALIUS-CV trial. Diabetes Care.
10 Repatha® (evolocumab) Prescribing Information, Amgen.
11 Sabatine, M. S., Giugliano, R. P., Keech, A. C., Honarpour, N., Wiviott, S. D., Murphy, S. A., Kuder, J. F., Wang, H., Liu, T., Wasserman, S. M., Sever, P. S., & Pedersen, T. R. (2017). Evolocumab and clinical outcomes in patients with cardiovascular disease. The New England Journal of Medicine, 376(18), 1713–1722.
12 Blumenthal, R. S., Morris, P. B., Gaudino, M., et al. (2026). 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. Circulation. https://doi.org/10.1161/CIR.0000000000001423
13 Blumenthal, R. S., Morris, P. B., Gaudino, M., et al. (2026). 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. Circulation.
14 Data on File. Amgen. 2025.
15 Data on File. Amgen. 2025.
16 Dent, R., Joshi, R., Djedjos, C. S., Legg, J., Elliott, M., Geller, M., Meyer, D., Somaratne, R., Recknor, C., & Weiss, R. (2016). Evolocumab lowers LDL-C safely and effectively when self-administered in the at-home setting. SpringerPlus, 5, 300.
17 Data on File. Amgen. 2026.
18 Data on File. Amgen. 2026.
19 Data on File. Amgen. 2026.
20 Data on File. Amgen. 2026.
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