<h3>Lead Author's Financial Disclosures</h3> Nothing to disclose. <h3>Study Funding</h3> None. <h3>Background/Synopsis</h3> Bempedoic acid is a first-in-class citrate lyase inhibitor that reduces atherogenic lipoproteins. There is limited data on the incidence of muscle-related adverse effects in statin-intolerant patients treated with bempedoic acid. <h3>Objective/Purpose</h3> To determine the effect of bempedoic acid on atherogenic lipoproteins in patients not on statins and whether statin-intolerant patients experience muscle-related adverse effects. <h3>Methods</h3> We performed a systematic review and meta-analysis of all published studies reporting the outcomes of bempedoic acid versus placebo in patients with hypercholesterolemia who were not on statins. All studies were included in the analysis of the lipoprotein effects (n=6), whereas only studies of statin-intolerant patients were included in the analysis of muscle-related adverse effects (n=4). <h3>Results</h3> The meta-analysis included 1,084 patients not on statins: 792 on bempedoic acid, and 292 on placebo. Four studies included only statin-intolerant patients (n=847): 629 on bempedoic acid and 218 on placebo. During a median follow-up of 12 weeks (range 4-24 weeks), bempedoic acid produced significant reductions in LDL-C (mean difference (MD) -25.7%, p<0.001), non-HDL cholesterol (MD -21.2%, p<0.001), and total cholesterol (MD -16.7%, p<0.001), compared to placebo with a similar risk of muscle-related adverse events (odds ratio (OR) 0.82, p=0.37), including myalgia (OR 0.71, p=0.32), muscle spasm (OR 1.08, p=0.84), weakness (OR 0.47, p=0.21), and muscle pain (OR 1.10, p=0.81). <h3>Conclusions</h3> Bempedoic acid decreases atherogenic lipoproteins in patients not taking statins and does not increase the incidence of muscle-related adverse events in statin-intolerant patients.