Drug Evolocumab Significantly Reduces Risk of Heart Attack

Cardiovascular diseases are the leading cause of death globally, representing around 32% of all deaths. Of these deaths, 85% were due to heart attacks and strokes (World Health Organization, 2025). Although Evolocumab was discovered in the late 2000s and was approved by the FDA in August 2015, use of it previously required the patient to have a history of diagnosed heart attacks and stroke, and the Evolocumab dose was designed to reduce the risk of further cardiovascular events. In August 2025, the US Food and Drug Administration (FDA) expanded the Evolocumab label for adults with increased Major Adverse Cardiovascular Events (MACE) risk from uncontrolled LDL cholesterol (Hayden, 2025). 

Low-density lipoprotein cholesterol, otherwise known as LDL cholesterol, is a type of lipoprotein, or particle for carrying fats to cells across the body. Excess LDL contributes to plaque buildup in arteries, known as atherosclerosis, which increases the risk of a stroke or heart attack (Cleveland Clinic, 2022). Statins, a class of medicine that reduces the body’s buildup of fatty plaques, are a more traditional way of lowering cholesterol. Including atorvastatin, fluvastatin, lovastatin, the medicine has recently been linked to muscle pain, mental fuzziness, and even liver damage in certain patients. These are common side effects of statin that can be mitigated with more effective therapies, such as evolocumab (Mayo Clinic, 2025).

Proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors are used to lower LDL cholesterol with hypercholesterolemia (high blood cholesterol). They are a highly effective class of injectable drugs that reduce LDL “bad” cholesterol by 50%-60%. (Pokhrel & Levine, 2019) The drug also reduces the risk of heart attacks and strokes. The number of doses each day are dependent on the patient’s age and medical condition. The possible side effects of evolocumab are comparatively more minor than those of statins; including sore throats, headaches, and soreness (Mayo Clinic, n.d.).

Evolocumab, a type of PCSK9, increases the number of the low-density lipoprotein receptor (LDL-R), a cell-surface protein that is found primarily on liver cells called hepatocytes. Hepatocytes express LDL-R, which bind to the LDL-Cholesterol (LDL-C) and remove it from the bloodstream. PCSK9 is a protein that controls the expression of LDL-R, and as a result affects LDL-C rates. The functional PCSK9 will attach to LDL-R cells on the surface of hepatocytes, preventing it from binding to and eliminating the LDL-C. To prevent PCSK9 slowing down the LDL-C elimination process, a monoclonal antibody is used here. Monoclonal antibodies like evolocumab are lab-made proteins that mimic the immune system’s ability to target specific cells. The protein is directed against PCSK9 and restrains it from binding to LDL-R cells. As a result, more available receptor cells will achieve a higher LDL elimination rate, and thus decrease the overall amount of LDL-C in bloodstreams (Kasichayanula et al., 2018).

The recent approval from the FDA was backed by a study across 5 years that closely monitored patients who have never had a heart attack or stroke. Out of 12,257 patients, half received Evolocumab while the other half received placebo, an inactive substance that appears genuine to the patient. Researchers (Bohula, et al.) tested patients without previous myocardial infarctions (heart attack) or strokes, since evolocumab reduces MACE among patients with previous diseases. Researchers followed up around 5 years with the patients. There were 747 (around 13.4%) MACE in the evolocumab group, fewer compared to 907 (16.2%) in the placebo group. The findings suggest that evolocumab reduces the risk of first cardiovascular events for people without previous Myocardial Infarctions (MIs) or strokes (Bohula et al., 2025).

The Treatment Satisfaction Questionnaire for Medication (TSQM) high levels of satisfaction among both patients and physicians using Evolocumab to treat high levels of LDL-C. Unlike traditional therapies, Evolocumab provides a targeted, safe, and non-statin option for patients with much fewer side effects — either to reduce risk of further MACEs, or prevent them altogether. (Sidelnikov et al., 2025). With the increasing prevalence of Evolocumab, the drug might play an increasingly important role in reducing risk of cardiovascular diseases and transforming the medical field. 

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References

Cleveland Clinic. (2022, October 27). LDL cholesterol: What it is & how to lower it. Cleveland Clinic. https://my.clevelandclinic.org/health/articles/24391-ldl-cholesterol

Mayo Clinic. (2025, March 11). Statin side effects: Weigh the benefits and risks. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/high-blood-cholesterol/in-depth/statin-side-effects/art-20046013

Pokhrel, B., & Levine, S. N. (2019, April 11). PCSK9 Inhibitors. Nih.gov; StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK448100/

Bohula, E. A., Marston, N. A., Bhatia, A. K., Gaetano, Leiter, L. A., Nicolau, J. C., Park, J.-G., Kuder, J. F., Murphy, S. A., Walsh, E., Wang, H., Blaha, V., Andrzej Budaj, Cornel, J. H., Assen Goudev, Kiss, R. G., Lorenzatti, A. J., Parkhomenko, A., Cyrille, M., & Paiva, G. (2025). Evolocumab in Patients without a Previous Myocardial Infarction or Stroke. New England Journal of Medicine. https://doi.org/10.1056/nejmoa2514428

Hayden E. K. (2025). FDA Expands Evolocumab Label for Adults With Increased MACE Risk From Uncontrolled LDL-C. The American Journal of Managed Care. https://www.ajmc.com/view/fda-expands-evolocumab-label-for-adults-with-increased-mace-risk-from-uncontrolled-ldl-c

Kasichayanula, S., Grover, A., Emery, M. G., Gibbs, M. A., Somaratne, R., Wasserman, S. M., & Gibbs, J. P. (2018). Clinical Pharmacokinetics and Pharmacodynamics of Evolocumab, a PCSK9 Inhibitor. Clinical Pharmacokinetics, 57(7), 769–779. https://doi.org/10.1007/s40262-017-0620-7

Sidelnikov, E., Jones, L. K., Debrosse, A., Okorozo, P., & Kalich, B. (2025). Insights from Patients and Physicians About Use of Evolocumab for LDL-C Management. Advances in Therapy, 42(10), 5088–5103. https://doi.org/10.1007/s12325-025-03322-4

Evolocumab (Subcutaneous Route) Description and Brand Names - Mayo Clinic. (n.d.). Www.mayoclinic.org. https://www.mayoclinic.org/drugs-supplements/evolocumab-subcutaneous-route/description/drg-20152627