Matthew Garrett PharmD candidate 2015, Mercer University College of Pharmacy
Evolocumab is a human monoclonal antibody that is still in clinical trials. Previous clinical trials have shown that evolocumab along with diet and statins lowers patient’s LDL levels. Evolocumab is a proprotein convertase subtilisin/kexin type 9 inhibitor, which leads to more low-density lipoprotein (LDL) receptors on the liver to uptake circulating LDL.1 Proprotein convertase subtilisin/kexin type 9 gene codes for proteins to regulate the amount of cholesterol in the bloodstream by controlling the amount of LDL receptors on a cell’s surface.2
Primary Outcome Measure: The primary end point was the efficacy and incidence of adverse events.
|Title: Efficacy and Safety of Evolocumab in Reducing Lipids and Cardiovascular Events3|
|Design||An open-label randomized controlled study
|Objective||To determine the efficacy and safety of evolvcumab|
|Study groups||Evolocumab plus standard therapy
Standard therapy alone
|Methods||Patients were randomly assigned in a 2:1 ratio. Evolocumab was administered subcutaneously at a dose of 420 mg once a month and, on the basis of patient choice, at a dose of either 140 mg every 2 weeks or 420 mg once a month.|
|Baseline Characteristics||Male 50%
North America 47%
Asia or South Africa 12.4%
|Results||The rate of cardiovascular events at 1 year was reduced from 2.18% in the standard-therapy group to 0.95% in the evolocumab group (P=0.003). As compared with standard therapy alone, evolocumab reduced the level of LDL cholesterol by 61%, from a median of 120 mg per deciliter to 48 mg per deciliter (P<0.001). Serious adverse events occurred in 222 patients (7.5%) in the evolocumab group and in 111 patients (7.5%) in the standard-therapy group.|
|Adverse Events||Common Adverse Events: Arthralgia 4.6%, headache 3.6%, limb pain 3.3%|
|Serious Adverse Events: Alanine or aspartate aminotransferase elevation 1%, creatinine kinase elevation 0.6%|
|Percentage that Discontinued due to Adverse Evens: 2.4%|
|Study Author Conclusions||The use of evolocumab plus standard therapy, as compared with standard therapy alone, significantly reduced LDL cholesterol levels and reduced the incidence of cardiovascular events in a prespecified but
exploratory analysis. The rate of adverse events were reported more frequently in the evolocumab group than in the standard therapy group.
This clinical trial has shown that standard therapy along with evolocumab is effective in lowering LDL levels and reducing cardiovascular events. This drug has not been approved by the Food and Drug Administration yet, but with more clinical trials showing its effectiveness evolocumab could be used to help reduce LDL levels. The incidence of adverse events was higher in the evolocumab group than the standard therapy group.
1. Blom D, Hala T, Bolognese M. A 52-Week Placebo-Controlled Trial of Evolocumab in Hyperlipidemia. New England Journal of Medicine. 2014;370(19):1809-1819. doi:10.1056/nejmoa1316222.
2. Genetics Home Reference. PCSK9 gene. 2015. Available at: http://ghr.nlm.nih.gov/gene/PCSK9. Accessed March 18, 2015.
3. Sabatine M, Giugliano R, Wiviott S. Efficacy and Safety of Evolocumab in Reducing Lipids and Cardiovascular Events. New England Journal of Medicine. 2015:150315080057008. doi:10.1056/nejmoa1500858.