What is Evolocumab (Repatha)?

From the Guidelines

Evolocumab should be used as an adjunctive therapy for patients with established cardiovascular disease or familial hypercholesterolemia who are receiving maximally tolerated statin therapy but require additional lowering of LDL cholesterol, as it has been shown to reduce LDL cholesterol by 59% and decrease cardiovascular events in high-risk patients. The medication is administered as a subcutaneous injection, typically 140 mg every two weeks or 420 mg once monthly, and works by blocking the PCSK9 protein, which normally binds to LDL receptors and leads to their degradation; by inhibiting this process, evolocumab increases the number of LDL receptors available on liver cells to remove LDL cholesterol from the bloodstream 1. Some key points to consider when using evolocumab include:

• Common side effects include injection site reactions, nasopharyngitis, and upper respiratory tract infections
• Patients should continue their prescribed statin therapy while using evolocumab unless otherwise directed by their healthcare provider
• The medication requires refrigeration before use but can be kept at room temperature for up to 30 days
• Evolocumab has demonstrated significant LDL cholesterol reductions of 55-75% in clinical trials and has been shown to reduce cardiovascular events in high-risk patients, as seen in the Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk (FOURIER) trial 1. The most recent and highest quality study, the 2022 standards of medical care in diabetes, supports the use of evolocumab as an adjunctive therapy for patients with ASCVD or familial hypercholesterolemia who are receiving maximally tolerated statin therapy but require additional lowering of LDL cholesterol 1.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Evolocumab Overview

• Evolocumab is a fully human monoclonal antibody that targets ProProtein Convertase Subtilisin/Kexin 9 (PCSK9) 2, 3
• PCSK9 is a circulating enzyme secreted by the liver that plays a key role in the LDL-Receptors (LDL-R) turnover 2
• Inhibiting PCSK9 is a new way to markedly reduce LDL-C, and evolocumab has been shown to significantly reduce LDL-C levels in clinical trials 2, 3

Clinical Efficacy and Safety

• The clinical efficacy and safety of evolocumab have been studied in several controlled trials versus placebo or versus active comparator (ezetimibe) during 12 to 76 weeks 2
• Evolocumab has been shown to reduce LDL-C up to 50 to 60% from baseline when added to statin therapy 2
• Evolocumab has also been shown to reduce other lipid parameters, including total cholesterol, non-HDL cholesterol, apolipoproteins A1 and B, lipoprotein(a), and triglycerides 3
• Safety and tolerance of evolocumab have been good, with rates of adverse events similar to those of controls in clinical trials 3

Patient Selection and Follow-up

• Appropriate candidates for evolocumab are individuals at high cardiovascular risk, including those with familial hypercholesterolemia and/or established cardiovascular disease, who are already on statin therapy 4
• Evolocumab monotherapy may be considered for individuals deemed statin-intolerant despite attempting several statins 4
• Patient willingness to self-inject evolocumab and issues concerning third-party coverage should be considered due to the current costs of evolocumab 4

Use in Acute Coronary Syndromes

• Evolocumab has been shown to be effective in reducing LDL-C levels in patients with acute coronary syndromes (ACS) when initiated during the in-hospital phase 5
• The EVOPACS trial demonstrated that evolocumab added to high-intensity statin therapy was well tolerated and resulted in substantial reduction in LDL-C levels, rendering >95% of patients within currently recommended target levels 5