Abstract 4371829: Efficacy of Bempedoic Acid Versus Placebo for Additional Lipid Lowering in Patients Receiving Background Statin Therapy: A Meta-Analysis of Randomized Controlled Trials

Introduction: Bempedoic acid, an oral ATP-citrate lyase inhibitor, is indicated as an adjunct to maximally tolerated statin therapy for patients with atherosclerotic cardiovascular disease (ASCVD) or heterozygous familial hypercholesterolemia (HeFH) who require additional LDL-C lowering. The American College of Cardiology/American Heart Association (ACC/AHA) guidelines recommend bempedoic acid as a nonstatin option for further LDL-C reduction in these populations, particularly when statin therapy alone is insufficient or not tolerated. Methodology: A systematic search of databases including PubMed, Google Scholar, ScienceDirect, Cochrane Library, and clinicaltrials.gov was conducted through May 2025. We included randomized trials comparing bempedoic acid plus maximally tolerated statin therapy with placebo plus background statin, reporting three key outcomes, including changes in non–HDL cholesterol, total cholesterol, or apolipoprotein B at 12 weeks, in patients with established atherosclerotic cardiovascular disease (ASCVD) and heterozygous familial hypercholesterolemia (HeFH). A meta-analysis was performed in RevMan 5.4.1 using a random-effects model to assess heterogeneity. Results: Three randomized controlled trials with a total of 3034 patients were included, comprising 2014 cases (mean age: 65.3 ± 9.1, male: 69.9%) and 1020 controls (mean age: 66.2 ± 8.8, male: 69.3%). A pooled analysis showed a significant non-HDL-C reduction in the Bempedoic acid group compared to the placebo [Mean difference (MD): -15.50 mg/dL; 95% CI, -18.95 to -12.04; p<0.0001]. Similarly, a significant reduction in total cholesterol levels (MD: -14.64 mg/dL; 95% CI, -21.42 to -7.85; p<0.00001) and apolipoprotein B levels (MD: -13.51 mg/dL; 95% CI, -15.72 to -11.29; p<0.00001) was noted. Conclusion: The addition of bempedoic acid compared with placebo resulted in a significant lowering of various cholesterol subfraction levels over 12 weeks. Our meta-analysis reiterates the efficacy of bempedoic acid as lipid-lowering therapy in patients with established ASCVD&HeFH. The ES-BempedACS trial is an ongoing trial that further compares the outcomes of bempedoic acid use in combination with statins in a large sample size. There is a need for large-scale RCTs to establish the inclusion of Bempedoic acid in guideline-directed lipid-lowering therapy.