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

- Mipomersen results in reduction in low-density lipoprotein cholesterol (LDL-C) by reducing apolipoprotein B-100.
- Randomized trials showed mipomersen reduces LDL-C in patients with dyslipidemia.
- This meta-analysis showed mipomersen improved all the lipid parameters but high-density lipoprotein cholesterol.
- Mipomersen increased risk of hepatic steatosis and elevation in alanine aminotransferase.

BackgroundLow-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.ObjectiveWe aimed to perform a meta-analysis of all published randomized controlled trials comparing safety and efficacy of mipomersen with placebo in adults with dyslipidemia.MethodsWe searched PUBMED, CENTRAL, and EMBASE from inception through March 2014 and used random-effects model to compute the effect size.ResultsWe 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 A1. 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 ≥10X upper limit of normal did not reach statistical significance (1.57; 0.32-7.6, P = .58).ConclusionMipomersen resulted in a significant improvement in lipid parameters except for HDL-C and increased the risks of injection-site reactions, flu-like symptoms, and hepatic steatosis compared with placebo.