Efficacy and safety of bempedoic acid for the treatment of hypercholesterolemia: A systematic review and meta-analysis

Abstract

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 Mantel-Haenszel method. Bempedoic acid significantly reduced total cholesterol (MD −14.94%; 95% CI −17.31%, −12.57%; p < 0.001), non-high-density lipoprotein cholesterol (MD −18.17%; 95% CI −21.14%, −15.19%; p < 0.001), low-density lipoprotein cholesterol (MD −22.94%; 95% CI −26.63%, −19.25%; p < 0.001), low-density lipoprotein particle number (MD −20.67%; 95% CI −23.84%, −17.48%; p < 0.001), apolipoprotein B (MD −15.18%; 95% CI −17.41%, −12.95%; p < 0.001), highdensity lipoprotein cholesterol (MD −5.83%; 95% CI −6.14%, −5.52%; p < 0.001), high-density lipoprotein particle number (MD −3.21%; 95% CI −6.40%, −0.02%; p = 0.049), and hsCRP (MD −27.03%; 95% CI −31.42%, −22.64%; p < 0.001). Bempedoic acid did not

Bempedoic acid safety analysis: Pooled data from four phase 3 clinical trials

“…This analysis reports combined safety data from four phase 3 clinical trials encompassing more than 3600 patients (.3000 from 52-week studies). The pooled nature of the analysis using individual patient data provides insight into the safety of bempedoic acid beyond currently published data and systematic reviews/meta-analyses that use summary information, [18][19][20][21][22] revealing a consistent profile across clinical trials and patient subgroups. Background LLT, which was used by the majority of patients, had no demonstrable effect on the safety or tolerability of bempedoic acid.…”

Novel Therapeutical Approaches to Managing Atherosclerotic Risk

“…The oxidation of LDL-C and subsequent incorporation into the walls of the arteries trigger inflammation of the arterial walls, the weakening of the atherosclerotic plaque and subsequent acute cardiovascular event; one of the main indices of inflammation is high sensitivity-C Reactive Protein (hs-CRP) [ 32 ]. The pivotal studies of bempedoic acid showed a reduction not only in LDL-C but also in hs-CRP [ 31 , 32 , 33 , 34 ]. That is why it might be a very useful and effective tool in statin intolerant patients.…”

“…In the CLEAR Harmony (Evaluation of Long-Term Safety and Tolerability of ETC-1002 in High-Risk Patients with Hyperlipidemia and High Cardiovascular Risk) study, patients who received maximally tolerated statin therapy administered with bempedoic acid had LDL-C levels significantly lower than placebo (mean difference, 18%), without an increase in serious adverse events [ 32 ]. Based on the pooled analysis of phase 3 trials in might reduce LDL-C by even 25% (is much more effective in statin intolerant patients) CRP by even 40% with acceptable safety profile [ 31 , 32 , 33 , 34 ].…”

Influence of Hyperproteinemia on Insect Innate Immune Function of the Circulatory System in Bombyx mori

“…Metabolic disorders of the circulatory system are typically characterized by the presence of abnormally increased or decreased metabolites in the circulating blood, which can cause many clinical diseases (e.g., hyperglycemia [17], hyperlipidemia [18], hypercholesterolemia [19,20], and hyperuricemia [21]). It is particularly interesting that patients with hyperproteinemia generally display metabolic changes (e.g., abnormal blood glucose and blood lipid levels) [4,5], and there is a significant change in the proportion of circulating blood cells [8,22].…”