Pharmacists' Guide to Evolocumab for Lowering LDL-C

Evolocumab (Repatha; Amgen) is part of a family of drugs called proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors. This medication is indicated to reduce the risk of myocardial infarction, risk of coronary revascularization, and risk of stroke in adult patients with cardiovascular disease. In addition, it is indicated for treatment of primary hyperlipidemia; reduction of lipoprotein cholesterol levels as an adjunct to healthy diet; and treatment of homozygous familiar hypercholesterolemia, in combination with the use of other low-density lipoprotein cholesterol (LDL-C)–lowering drugs and in conjunction with a healthy diet.¹

AI-generated image of cholesterol and heart disease | Image credit: charnsitr | stock.adobe.com

Evolocumab binds to the PCSK9 and inhibits it from binding to the LDL receptors, which prevents PCKS9-medicated LDL-receptor degradation and recycles them back to the liver cell surface. This recycling causes absorption of more LDL particles from the body. The maximum effects are seen with 4 hours of administration.¹

Evolocumab is administered as a subcutaneous injection, available as a 140 mg/ml autoinjector, 140 mg/ml prefilled syringe, and 420 mg/3.5ml solution for an on-body infuser. The dose, depending on the indication, may start from 140 mg every 2 weeks or 420 mg once monthly. The injection is recommended to be administered in the abdomen, thighs, or upper arms and patients should be counseled that the medication needs to be refrigerated. Before use, it should be allowed to warm up to room temperature for at least 30 to 45 minutes, depending on whether the patient is using the syringe or the infusor. If not kept refrigerated, it must be used within 30 days.¹

Adverse events may include back pain, injection site reactions, nasopharyngitis, and upper respiratory tract infections. Because it is a monoclonal antibody, renal function is not expected to be affected by this medication. Patients should be educated to report any flu-like symptoms or major bruising to their provider, particularly if these symptoms do not resolve after a while.¹

According to study results published in The New England Journal of Medicine and involving 27,564 participants, evolocumab was able to reduce median LDL-C to 30 mg/dL and reduce cardiovascular risk. Patients either received evolocumab 140 mg every 2 weeks or 420 mg monthly. The study’s primary and secondary end points were focused on cardiovascular event reduction, death as a result of cardiovascular disease, stroke, and myocardial infarction.²

At 48 weeks, the study found that the least-squares mean percentage reduction in LDL-C with evolocumab was 59%, from a median baseline of 92 mg/dL to 30 mg/dL. The results were consistent across key subgroups, including patients in the lowest quartile for baseline LDL-C levels.²

Pharmacists can play a crucial role in educating patients on the proper storage and administration of evolocumab. Patients should also be educated about warnings, precautions, and what to watch for, including adverse effects, and how to report them.

It is important for patients with high LDL-C to be treated properly. If statins do not work as effectively as needed, options such as evolocumab can be added to the treatment regimen. In clinical trials, about 84% of patients lowered their LDL-C with evolocumab in addition to a statin over the course of a month. The majority of these patients were able to reduce their LDL to below 55 mg/dl. Such reduction is proven to reduce the chance of heart attack by 27%. Those impacted by familial hypercholesterolemia may not have much benefit from statin use and may be dependent on evolocumab.³

Evolocumab represents yet another option for patients at high risk of cardiovascular events. By reducing of LDL-C levels, patients should be able to reduce their chances of cardiovascular death.

REFERENCES

1. Repatha. Prescribing Information. Updated September 2021. Accessed August 27, 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/125522s043lbl.pdf

2. Sabatine MS, Giugliano RP, Keech AC, et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017;376:1713-1722. doi:10.1056/NEJMoa1615664

3. What is Repatha? Repatha website. Accessed August 27, 2024. https://www.repatha.com/what-is-repatha