Safety and efficacy of bempedoic acid: a systematic review and meta-analysis of randomised controlled trials

• Published in: Cardiovascular diabetology 2023-11, Vol.22 (1), p.324-324, Article 324
• Main Authors: De Filippo, Ovidio, D'Ascenzo, Fabrizio, Iannaccone, Mario, Bertaina, Maurizio, Leone, Attilio, Borzillo, Irene, Ravetti, Emanuele, Solano, Andrea, Pagliassotto, Ilaria, Nebiolo, Marco, Bruno, Francesco, Giacobbe, Federico, Muscoli, Saverio, Monticone, Silvia, Brizzi, Maria Felice, Biondi Zoccai, Giuseppe, De Ferrari, Gaetano Maria
• Format: Article
• Language: English
• Subjects: Acids; Angina; Atherosclerosis; Bempedoic acid; Cardiovascular disease; Cardiovascular outcomes; Cholesterol; Cholesterol, LDL; Clinical trials; Collaboration; Diabetes mellitus; Drug dosages; Enzymes; Gout; Gout - chemically induced; Gout - drug therapy; High density lipoprotein; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - adverse effects; Hypercholesterolemia; Hypotheses; Hypothesis testing; Intervention; Lipoproteins; Low density lipoprotein; Meta-analysis; Myocardial infarction; Myocardial Infarction - diagnosis; Myocardial Infarction - drug therapy; Placebos; Randomized Controlled Trials as Topic; Risk factors; Safety; Statins; Systematic review; Treatment Outcome
• ISSN: 1475-2840; 1475-2840
• DOI: 10.1186/s12933-023-02022-z

Bempedoic Acid (BA) is a novel Lipid-Lowering Therapy (LLT). We performed a systematic review and meta-analysis to assess the efficacy and safety of BA in patients with hypercholesterolemia. PubMed, Scopus, and Cochrane library databases were searched for randomised controlled trials evaluating the efficacy and/or safety of BA compared with placebo. Trials investigating dosages other than 180 mg/die were excluded. Major adverse cardiovascular events (MACE) were the primary efficacy endpoint. LDL-cholesterol reduction was the primary laboratory endpoint. Pre-specified safety endpoints included muscle-related adverse events, new-onset diabetes, and gout. The protocol was registered on PROSPERO (temporary ID:399,867). Study search identified 275 deduplicated results. 11 studies, encompassing 18,315 patients (9854 on BA vs 8461 on placebo/no treatment) were included. BA was associated with a reduced risk of MACE (OR 0.86, 95% CI 0.79-0.95), myocardial infarction (OR 0.76, 95% CI 0.64-0.88) and unstable angina (OR 0.69, 95% CI 0.54-0.88) compared to control, over a median follow up of 87 (15-162) weeks. BA was associated with a reduction of LDL-Cholesterol (mean difference [MD]-22.42,95% CI - 24.02% to - 20.82%), total cholesterol (- 16.50%,95% - 19.21% to - 13.79%), Apo-B lipoprotein (- 19.55%, - 22.68% to - 16.42%) and high-sensitivity CRP (- 27.83%, - 31.71% to - 23.96%) at 12 weeks. BA was associated with a higher risk of gout (OR 1.55, 95% CI 1.27-1.90) as compared with placebo. Efficacy on laboratory endpoints was confirmed, with a variable extent, across patients on statin or ezetimibe background therapy. The improved cholesterol control achieved with BA translates into a reduced risk of MACE, including myocardial infarction and coronary revascularisation. The drug has a satisfactory safety profile except for an increased risk of gout.