The first large-scale real-world study to assess lipid management and the impact of evolocumab (Repatha), a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, on cardiovascular (CV) outcomes in clinical practice is set to be initiated by Amgen in collaboration with the Duke Clinical Research Institute (DCRI).

The study, known as the Cardiovascular Multi-dimensional Observational Investigation of the Use of PCSK9 inhibitors (cvMOBIUS), will examine the effectiveness of evolocumab on 5-year CV outcomes in real-world practice.

cvMOBIUS will be conducted across the United States and Canada and will begin patient enrollment this month. A prospective observational registry of 8500 adults eligible for treatment with evolocumab will be followed for 5 years. Additionally, an electronic health record-based registry will follow a broader population of adults hospitalized with atherosclerotic cardiovascular disease (ASCVD) at participating sites.

"Cardiovascular disease is one of the most significant public health issues facing our country today. Gathering robust, large-scale data from diverse patients will better inform lipid management and help decrease the burden of cardiovascular disease in these high-risk patients," Ann Marie Navar, MD, PhD, assistant professor of medicine at the Duke University School of Medicine and member of the DCRI, said in a statement. "The clinical evidence supporting the efficacy and safety of PCSK9 inhibitors in patients with cardiovascular disease is well established, but we still have a lot to learn about the benefits of these medicines in the real world."

Patients who have experienced a recent ASCVD event are at higher risk of experiencing another CV event, especially within the first year. According to Amgen, lipid lowering is 1 of the key approaches for reducing a patient’s risk for secondary events. Based on large randomized trials, major professional cardiology societies acknowledge that lower is better when it comes to low-density lipoprotein cholesterol (LDL-C) management in patients who have experienced myocardial infarction and other ASCVD events.

Evolocumab is a human monoclonal antibody that inhibits PCSK9 by binding to the proprotein and inhibiting circulating PCSK9 from binding to the LDL receptor (LDLR), preventing PCSK9-mediated LDLR degradation, and permitting LDLR to recycle back to the liver cell surface. By inhibiting the binding of PCSK9 to LDLR, evolocumab increases the number of LDLRs available to clear LDL from the blood, thereby lowering LDL-C levels.

LDL-C is one of the most important modifiable risk factors for CV disease, so lipid management is an essential element in reducing future CV events and improving clinical outcomes for high-risk patients, according to study authors. The study registry will examine how care is being delivered in clinical practice to patients.

Two large randomized outcome trials, including the evolocumab cardiovascular outcomes (FOURIER) study, have previously demonstrated that innovative therapies like PCSK9 inhibitors lower LDL-C levels and can reduce the risk of heart attacks in high-risk patients with established CV disease. Additionally, the VESALIUS-CV trial, which began in March 2019, is an ongoing randomized outcomes trial designed to evaluate the long-term effects of evolocumab for a minimum of 4 years in patients without a prior heart attack or stroke.

The study will generate real-world evidence to help researchers demonstrate that PCSK9 inhibitors can be beneficial to very high-risk patients and can help prevent recurrent CV events.

Reference
  1. Amgen And The Duke Clinical Research Institute Announce Initiation Of First Large-Scale Registry To Evaluate Real-World Lipid Management And The Effectiveness Of PCSK9 Inhibitors [press release]. Thousand Oaks, CA. Amgen website. Published November 15, 2019. https://www.amgen.com/media/news-releases/2019/11/amgen-and-the-duke-clinical-research-institute-announce-initiation-of-first-large-scale-registry-to-evaluate-real-world-lipid-management-and-the-effectiveness-of-pcsk9-inhibitors/. Accessed November 18, 2019.