Abstract 4372102: Bempedoic Acid Lowers LDL-C and Reduces Risk of Major Cardiovascular Events in Hypercholesterolemia: Meta-Analysis of 13 Randomized Controlled Trials

Abstract

Introduction: Hypercholesterolemia drives atherosclerotic cardiovascular disease. Bempedoic acid (BA) lowers low-density-lipoprotein cholesterol (LDL-C) by inhibiting ATP-citrate-lyase, providing a non-statin option for patients who need additional lipid control. Hypothesis: We expected BA to improve atherogenic lipids and major adverse cardiovascular events (MACE) without raising cardiovascular (CV) mortality and with an acceptable safety profile. Aims: To measure the pooled effect of BA on (1) LDL-C, (2) non-HDL-C, (3) high-sensitivity C-reactive protein (hsCRP) and to compare clinical outcomes for (4) MACE, (5) CV mortality, and (6) hyperuricemia versus placebo. Methods: A systematic search of PubMed, Embase, MEDLINE, Google Scholar and ClinicalTrials.gov through 1 April 2025 identified randomized controlled trials (RCTs) of BA versus placebo in adults with hypercholesterolemia. Data were extracted into a spreadsheet, and analyses were performed with RevMan 5.4. Results: 13 RCT's with 22345 patients met the inclusion criteria. BA produced robust lipid and inflammatory improvements. LDL-C fell by 24.3 % (95 % CI −27.8 to −20.9), non-HDL-C by 19.8 % (95 % CI −25.0 to −14.6), and hsCRP by 26.7 % (95 % CI −39.6 to −13.7). These changes translated into a 19 % relative reduction in MACE (RR 0.81, 95 % CI 0.68–0.96), while CV mortality was unchanged (RR 0.87, 95 % CI 0.53–1.43). As anticipated, hyperuricemia risk almost doubled with BA (RR 1.93, 95 % CI 1.75–2.14). Conclusion: BA consistently lowers LDL-C, non-HDL-C and systemic inflammation and reduces MACE without affecting CV mortality. The main safety concern is higher hyperuricemia, which appears manageable with monitoring. These findings support BA as an effective add-on therapy for patients who are statin-intolerant or need further lipid reduction, while highlighting the need for longer trials to assess mortality benefits and long-term safety.