1 research outputs found
Efficacy and safety of bempedoic acid for the treatment of hypercholesterolemia: A systematic review and meta-analysis
Background: Bempedoic acid is a first-in-class lipid-lowering drug recommended by guidelines for the treatment of hypercholesterolemia. Our objective was to estimate its average effect on plasma lipids in humans and its safety profile.
Methods and findings: We carried out a systematic review and meta-analysis of phase II and III randomized controlled trials on bempedoic acid (PROSPERO: CRD42019129687). PubMed (Medline), Scopus, Google Scholar, and Web of Science databases were searched, with no language restriction, from inception to 5 August 2019. We included 10 RCTs (n = 3,788) comprising 26 arms (active arm [n = 2,460]; control arm [n = 1,328]). Effect sizes for changes in lipids and high-sensitivity C-reactive protein (hsCRP) serum concentration were expressed as mean differences (MDs) and 95% confidence intervals (CIs). For safety analyses, odds ratios (ORs) and 95% CIs were calculated using the MantelβHaenszel method. Bempedoic acid significantly reduced total cholesterol (MD β14.94%; 95% CI β17.31%, β12.57%; p < 0.001), non-high-density lipoprotein cholesterol (MD β18.17%; 95% CI β21.14%, β15.19%; p < 0.001), low-density lipoprotein cholesterol (MD β22.94%; 95% CI β26.63%, β19.25%; p < 0.001), low-density lipoprotein particle number (MD β20.67%; 95% CI β23.84%, β17.48%; p < 0.001), apolipoprotein B (MD β15.18%; 95% CI β17.41%, β12.95%; p < 0.001), high-density lipoprotein cholesterol (MD β5.83%; 95% CI β6.14%, β5.52%; p < 0.001), high-density lipoprotein particle number (MD β3.21%; 95% CI β6.40%, β0.02%; p = 0.049), and hsCRP (MD β27.03%; 95% CI β31.42%, β22.64%; p < 0.001). Bempedoic acid did not significantly modify triglyceride level (MD β1.51%; 95% CI β3.75%, 0.74%; p = 0.189), very-low-density lipoprotein particle number (MD 3.79%; 95% CI β9.81%, 17.39%; p = 0.585), and apolipoprotein A-1 (MD β1.83%; 95% CI β5.23%, 1.56%; p = 0.290). Treatment with bempedoic acid was positively associated with an increased risk of discontinuation of treatment (OR 1.37; 95% CI 1.06, 1.76; p = 0.015), elevated serum uric acid (OR 3.55; 95% CI 1.03, 12.27; p = 0.045), elevated liver enzymes (OR 4.28; 95% CI 1.34, 13.71; p = 0.014), and elevated creatine kinase (OR 3.79; 95% CI 1.06, 13.51; p = 0.04), though it was strongly associated with a decreased risk of new onset or worsening diabetes (OR 0.59; 95% CI 0.39, 0.90; p = 0.01). The main limitation of this meta-analysis is related to the relatively small number of individuals involved in the studies, which were often short or middle term in length.
Conclusions: Our results show that bempedoic acid has favorable effects on lipid profile and hsCRP levels and an acceptable safety profile. Further well-designed studies are needed to explore its longer-term safety