Safety and efficacy of ETC-1002 in hypercholesterolaemic patients: A meta-analysis of randomised controlled trials

Abstract

Background: Due to the myopathic adverse events of statins, safer alternatives are being studied. Bempedoic acid (ETC-1002) is a novel low-density lipoprotein cholesterol (LDL-C)-lowering agent, currently under trial in hypercholesterolaemic patients. Aim: To investigate the tolerability and efficacy of ETC-1002 in hypercholesterolaemic patients through a systematic review of published randomised controlled trials (RCTs). Methods: Five databases were searched for RCTs that investigated the safety and efficacy of ETC-1002 in hypercholesterolaemic patients. The retrieved search results were screened, and then data were extracted and analysed (as mean difference [MD] or odds ratio [OR]) using the RevMan software. Results: Five RCTs (625 hypercholesterolaemic patients) were identified. ETC-1002 was superior to placebo in terms of percentage changes from baseline in serum levels of LDL-C (MD -26.58, 95% confidence interval [CI] -35.50 to -17.66, p < 0.0001), non-high-density lipoprotein cholesterol (MD -21.54, 95% CI -28.48 to -14.6, p < 0.00001), and apolipoprotein-B (MD -15.97, 95% CI -19.36 to -12.57, p < 0.0001). When compared to ezetimibe, ETC-1002 was superior in reducing LDL-C (-30.1 ± 1.3 vs. -21.1 ± 1.3). Regarding safety, ETC-1002 did not increase the risk of all adverse events (OR 0.58, 95% CI 0.37-0.91, p = 0.02) and arthralgia (OR 0.32, 95% CI 0.13-0.81, p = 0.02) compared to placebo. All other adverse events including myalgia, headache, and urinary tract infections were similar between ETC-1002 and placebo groups. The evidence certainty in the assessed outcomes was moderate to high except for lipoprotein(a), free fatty acids, and very low-density lipoprotein particle number (very low certainty). Conclusions: ETC-1002 is a safe and effective lipid-lowering agent and may be a suitable alternative in statin-intolerant patients. Well-designed studies are needed to explore the long-term safety and efficacy of ETC-1002 in these patients.