Efficacy and safety of mipomersen in treatment of dyslipidemia: A meta-analysis of randomized controlled trials

BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) is the primary target of lipid-lowering therapy in people at risk for cardiovascular diseases. Mipomersen inhibits apolipoprotein B-100 (apoB) synthesis and causes reduction in LDL-C by reducing apoB. OBJECTIVE: We aimed to perform a meta-analysis of all published randomized controlled trials comparing safety and efficacy of mipomersen with placebo in adults with dyslipidemia. METHODS: We searched PUBMED, CENTRAL, and EMBASE from inception through March 2014 and used random-effects model to compute the effect size. RESULTS: We identified 8 randomized controlled trials (n = 462). Mipomersen compared with placebo significantly reduced LDL-C by 32.37% (95% confidence interval, 25.55-39.18; P < .00001), total cholesterol by 24.18% (18.54-29.83; P < .00001), very low density lipoprotein cholesterol by 21.59% (9.16-34.02; P = .0007), non high-density lipoprotein cholesterol (HDL-C) by 30.83% (23.92-37.74; P < .00001), and triglycerides by 36.26% (22-50.54; P < .00001). It also significantly reduced apoB, lipoprotein(a), and apolipoprotein Al. However, mipomersen did not significantly change HDL-C levels. In safety analysis, mipomersen compared with placebo increased the risks of injection-site reaction (risk ratio, 2.05; 95% confidence interval, 1.39-3.04; P = .0003), flu-like symptoms (1.63; 1.22-2.17; P = .0008), alanine aminotransferase >= 3X upper limit of normal (4.44; 1.67-11.86; P = .003), and hepatic steatosis (3.85, 1.39-10.67; P = .01). The risks of alanine aminotransferase tranferase >= 10X upper limit of normal did not reach statistical significance (1.57; 0.32-7.6, P = .58). CONCLUSION: Mipomersen resulted in a significant improvement in lipid parameters except for 1--ML-C and increased the risks of injection-site reactions, flu-like symptoms, and hepatic steatosis compared with placebo. (C) 2015 National Lipid Association. All rights reserved.