Alirocumab in the Treatment of Hypercholesterolemia

Abstract

ABSTRACT:The role of low-density lipoprotein cholesterol (LDL-C) in the pathophysiology of atherosclerosis is well recognized, and statin therapy represents the standard of care for LDL-C lowering and reduction of cardiovascular risk. However, many patients fail to achieve LDL-C goals, whereas others are intolerant to statins due to side effects. Unfortunately, until recently, the efficacy of other nonstatin LDL-C-lowering agents was limited, achieving an LDL-C reduction of no more than 20%. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors represent a new class of LDL-lowering agents, producing large reductions in LDL-C. Alirocumab is a PCSK9 inhibitor, which was recently approved by the Food and Drug Administration as an adjunct to diet and maximally tolerated statin therapy for treatment of adults with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease who require additional lowering of LDL-C levels. This review aims to provide the current clinical and scientific data pertaining to the treatment of hypercholesterolemia with alirocumab.

Lipid-lowering interventions targeting proprotein convertase subtilisin/kexin type 9 (PCSK9): an emerging chapter in lipid-lowering therapy

“…Moreover, as compared with placebo, alirocumab reduced levels of apolipoprotein B by 54%, reduced levels of total cholesterol by 37.5%, reduced levels of non-HDL-C by 52.3%, reduced levels of lipoprotein (a) by 25.6% and reduced levels of fasting triglycerides by 17.3%. On the other hand, as compared with placebo, alirocumab, raised levels of HDL-C by 4.6% and raised levels of apolipoprotein A1 by 2.9% [ 24 , 25 ].…”

“…In a post hoc analysis, alirocumab, as compared with placebo, reduced the rate of major adverse cardiovascular events (death from coronary heart disease, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization) by 48% (1.7 vs 3.3%; 95% CI: 0.31–0.90; nominal p =0.02) [ 24 , 25 ].…”

“…In a study, which included patients with statin intolerance at moderate to high cardiovascular risk, treatment with alirocumab caused a mean LDL-C reduction of 45.0%, whereas treatment with ezetimibe decreased mean LDL-C by 14.6% (mean difference 30.4%, p <0.0001). Skeletal muscle-related adverse events were less frequent in the alirocumab group, as compared to a group of patients who were rechallenged with atorvastatin (hazard ratio 0.61, p =0.042) [ 25 , 26 ].…”

“…In one study, treatment with alirocumab led to discontinuation of lipoprotein apheresis in 63.4% of patients with HeFH, who were previously undergoing regular apheresis. Furthermore, the frequency of apheresis was at least halved in 92.7% of patients [ 25 , 27 ].…”

Targeting Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9): A New Promising Approach for the Management of Hypercholesterolemia

“…The human PCSK9 gene is located in the human chromosome 1p32.3 and encodes a 692-amino acid inactive glycoprotein, which undergoes an intramolecular self-catalytic cleavage in the endoplasmic reticulum [3]. trial, alirocumab, administered on top of maximally tolerated dose of statin, alone or in combination with other lipid-lowering agents, caused an additional 61.9% reduction in LDL-C levels, as compared with placebo [18,19]. …”