Therapeutic Potential and Critical Analysis of the PCSK9 Monoclonal Antibodies Evolocumab and Alirocumab

Objective: To review the mechanism of action for PCSK9 monoclonal antibodies and critically evaluate the therapeutic potential of evolocumab and alirocumab in the treatment of hypercholesterolemia. Data Sources: Ovid MEDLINE search from 1980 to August 2015 using the terms PCSK9, evolocumab, and alirocumab with forward and backward citation tracking. Study Selection and Data Extraction: English-language trials and studies assessing the mechanism, efficacy, or safety of PCSK9 monoclonal antibodies were included. Data Synthesis: PCSK9 monoclonal antibodies have a potent ability to reduce low-density lipoprotein (LDL) by almost 50% in controlled trials: −47.49% (95% CI = −69.6% to −25.4%). They have an acceptable safety profile with no significant elevations in Creatine Kinase (CK) (odds ratio [OR] = 0.72; 95% CI = 0.54 to 0.96) or serious adverse events (OR = 1.01; 95% CI = 0.87 to 1.18), and preliminary evidence suggests reductions in myocardial infarction (OR = 0.49; 95% CI = 0.26 to 0.93). Although it is effective in several familial hypercholesterolemia (FH) patient types, it does not work in homozygous patients with dual allele LDL receptor negative polymorphisms or those who are homozygous for autosomal recessive hypercholesterolemia. Conclusions: Although not preferred over statins because of limited clinical trial evidence of cardiovascular event reductions, dosing convenience, and expense, PCSK9 monoclonal antibodies will have a prominent role to play in the treatment of hypercholesterolemia, especially in patients needing large LDL reductions, including patients with many types of FH.