Evaluating the effects of bempedoic acid on lipid profiles and cardiovascular risk: An umbrella review of meta-analyses.

Background: This umbrella review aims to synthesize evidence from previously conducted meta-analyses and review articles to assess the effects of bempedoic acid on lipid profile and cardiovascular events.

Methods: While adhering to the Preferred Reporting Items for Overviews of Reviews guidelines, PubMed, Google Scholar, Web of Science, and Scopus were searched from the database inception to June 2024 to identify relevant articles. The outcomes were total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL cholesterol, triglyceride (TAG), apolipoprotein B (APOB), high-sensitivity CRP (hs-CRP), major cardiovascular events (MACE), cardiovascular mortality, and myocardial infarction (MI). A corrected covered area (CCA) assessment was performed to determine overlap among reviews. Each included review was assessed for its quality and rigor via the AMSTAR-2 tool.

Results: From 18,297 articles identified during the literature search, 18 meta-analyses were included. A significant overlap was noted across studies with a corrected cover area of 44.4%. Bempedoic acid's effects on cardiovascular outcomes and lipid levels have been extensively studied. For cardiovascular mortality, the evidence is mixed: Goyal et al.²¹ reported a risk ratio (RR) of 0.81 (95% CI 0.61-1.08) suggesting a potential benefit, while other studies, such as De Filippo et al.²⁶ and Zhang et al.²⁴, indicate no significant association. In terms of MACE, 11 reviews show a consistent trend toward reduced risk, with RRs between 0.75 and 0.88. Bempedoic acid also appears to significantly reduce the risk of MI, with RRs and odds ratios (ORs) around 0.76. Evidence on unstable angina suggests a lower risk, although some studies do not reach statistical significance. For coronary revascularization, the data show a reduced risk, with RRs ranging from 0.74 to 0.82. Studies on coronary non-revascularization also indicate a significant risk reduction with RRs and ORs of 0.41. Regarding lipid levels, bempedoic acid consistently reduces LDL cholesterol (mean differences [MDs] from -17.5% to -33.91%), total cholesterol (MDs from -12.69% to -34.41%), and non-HDL cholesterol (MDs from -12.3% to -23.27%). The effects on HDL cholesterol are less consistent (MDs from -1.29% to -5.18%), and triglyceride levels show variable results (MDs from -8.35% to +5.23%).

Conclusion: Our findings show that bempedoic acid significantly reduces the risk of MACE, nonfatal MI, coronary and noncoronary revascularization, and hospitalizations for unstable angina. While results on cardiovascular mortality are mixed, suggesting a need for further study, bempedoic acid proves to be an effective treatment for improving lipid profiles and reducing cardiovascular events, especially in patients who cannot tolerate statins. It presents a valuable option for cardiovascular risk management, potentially enhancing patient outcomes and quality of life. Further research is needed to assess its long-term benefits and broader applicability.