Evaluation of the Potential Role of Alirocumab in the Management of Hypercholesterolemia in Patients with High-Risk Cardiovascular Disease.

Abstract

A high level of low-density lipoprotein cholesterol (LDL-C) has proved to have a positive correlation with mortality from cardiovascular disease, and it is the key modifiable risk factor for cardiovascular disease. Lowering levels of LDL-C with statins reduces both vascular morbidity and mortality; however, myalgias occur in 10% to 15% of patients, and many patients managed with statins achieve suboptimal levels of LDL-C. The injectable drug alirocumab-the first of a new class of drugs called proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors-is a monoclonal antibody to the PCSK9 gene, which regulates LDL receptor expression and circulating levels of LDL-C. In this review, we evaluated the efficacy and safety of alirocumab and its potential role in the management of patients with high-risk cardiovascular disease. Data were gathered from articles indexed in the PubMed database (2006-April 2015). All English-language, prospective, randomized, double-blinded trials evaluating the efficacy of alirocumab, as a monotherapy or in combination with statins, for treatment of hypercholesterolemia were identified. Five clinical trials were evaluated, and the results from these studies revealed that the use of alirocumab, both as monotherapy or in combination with statins, significantly reduced LDL-C levels. Patients treated with alirocumab, with or without statins, were more likely to achieve LDL-C goals of less than 100 or 70mg/dl compared with placebo. Despite its ability to lower LDL-C level, one study did not show any antiinflammatory activity (i.e., reduced C-reactive protein level) among patients who received alirocumab; however, more clinical trials will be needed to further assess this effect. Alirocumab also appears to cause regression of plaque. The most commonly reported adverse effect was mild injection-site reaction. With increased odds of statin discontinuation among patients taking high-intensity statins, alirocumab will contribute to atherosclerotic cardiovascular disease risk reduction. However, morbidity and mortality data, as well as long-term safety data, are pending. Therefore, we propose that alirocumab will better serve as an adjuvant therapy for the management of hypercholesterolemia in patients at high risk for cardiovascular events. As with all new promising injectable drugs, cost will also be a key consideration.