OBJECTIVES: The objective of this investigation was toassess the evidence base by performing a systematic review of randomized controlled trials of Mipomersen for treatment of hypercholesteremia. METHODS: Studies published in English language were collated from PubMed and Cochrane databases using validated search strategies. Pre-specified inclusion/exclusion were employed to identify randomized controlled trials (RCTs), including Mipomersen based therapy. Two researchers independently screened the studies and extracted the data. Analysis of comparable outcomes was performed using random-effects model to calculate summary weighted mean difference (WMD) and 95% CI using statistical software R. RESULTS: Nine studies were finally included for data extraction. Overall effect size (WMD(95%CI)) were -0.42 (-0.66,-0.18),-0.24 (-0.37,0.12), -44.18 (-52.74,-35.63), -55.80 (-77.36,-34.24) and 0.16(-0.01,0.33) for Apo B, VLDL, LDL, Non-HDL, and HDL respectively. Mipomersen was associated with a reduction in LDL-C concentrations from baseline at the primary efficacy time point. The mean percentage change from baseline in LDL-C concentration was significantly greater with Mipomersen than with placebo. For the secondary and tertiary outcome measures, percentage changes from baseline were significantly greater with Mipomersen than with placebo for apo B, total cholesterol, non-HDL-C. Mipomersen treatment also resulted in a significant percentage reduction when compared with the placebo group for lipoprotein (a) concentration and LDL-C: HDL-C ratio. The most common adverse events were injection-site reactions, influenza-like symptoms, patients in Mipomersen group, increase in intrahepatic triglyceride content, increased ALT concentrations. CONCLUSIONS: The findings show that evidence supports Mipomersen being safe and effective intervention as an adjunctive drug for lowering LDL-C.