Efficacy and outcomes of bempedoic acid versus placebo in patients with hypercholesterolemia: an updated systematic review and meta-analysis of randomized controlled trials

Abstract

Introduction: Bempedoic acid (BA) has shown varied efficacy in managing hyperlipidemia. We conducted the most extensive up-to-date meta-analysis, the first to include recent studies by Nissen et al., which boast the largest sample size.

Methods: Literature search was done on Medline, EMBASE, and Cochrane Library. The primary endpoint was a change in low-density lipoprotein-cholesterol (LDL-C) levels, while secondary endpoints encompassed changes in lipid parameters, clinical endpoints, and safety endpoints. The least-square mean (LSM) percent change was utilized for lipid changes, with statistical significance set at P < 0.05.

Results: This analysis included 12 randomized control trials with 22,249 participants. BA exhibited a substantial reduction in LDL-C levels [LSM % change, -24.34; 95% confidence interval (CI), -27.80 to -20.88; P < 0.0001], total cholesterol levels (LSM % change, -16.62; 95% CI, -21.70 to -11.54; P < 0.00001) and high-density lipoprotein-cholesterol (HDL-C) levels (LSM % change, -4.22; 95% CI, -5.51 to -2.92; P < 0.00001) compared to the placebo.

Conclusions: BA significantly lowers LDL-C, total cholesterol, HDL-C, non-HDL-C, high sensitivity C reactive protein, and apolipoprotein levels.

Keywords: bempedoic acid; cardiovascular outcomes; coronary artery disease; hyperlipidemia; meta-analysis; prevention.

Fig. 1

Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) flow diagram for identification of studies included in the meta-analysis.

Fig. 2

Individual and pooled analysis for lipid parameters illustrating the efficacy of BA compared to placebo therapy in terms of lipid parameters. The mean difference and risk ratio (RR) with their 95% confidence interval (CI) are displayed using a logarithmic scale, with the box size scaling in accordance with the sample size. The diamond symbolizes the combined or overall effect. (a) LDL mean percent change (ungrouped). (b) LDL mean percent change (subgroup analysis). (c) TC (ungrouped). (d) TC (subgrouped). (e) Non-HDL-C (ungrouped). (f) Non-HDL-C (subgrouped). (g) hsCRP (ungrouped). (h) hsCRP (subgrouped). (i) HDL-C. (j) ApoB (ungrouped). (k) ApoB (subgrouped). (l) Triglycerides. Apo B, abetalipoprotein B; BA, bempedoic acid; HDL-C, high-density lipoprotein- cholesterol; hsCRP, high-sensitivity C-reactive protein; LDL, low-density lipoprotein; TC, total cholesterol.

Fig. 3

Individual and pooled analysis illustrating the clinical efficacy of BA compared to placebo therapy in terms of the clinical endpoints. The mean difference and risk ratio (RR) with their 95% confidence interval (CI) are displayed using a logarithmic scale, with the box size scaling in accordance with the sample size. The diamond symbolizes the combined or overall effect. (a) Coronary revascularization. (b) Noncoronary revascularization. (c) MI. (d) Hospitalization for unstable angina. (e) MACE. (f) ACM. (g) Cardiovascular-related mortality. (h) Hospitalization for heart failure. (i) Stroke. ACM, all-cause mortality; BA, bempedoic acid; MACE, major adverse cardiovascular events; MI, myocardial infarction.

Fig. 4

Individual and pooled analysis illustrating the efficacy of BA compared to placebo therapy in terms of the safety endpoints. The mean difference and risk ratio (RR) with their 95% confidence interval (CI) are displayed using a logarithmic scale, with the box size scaling in accordance with the sample size. The diamond symbolizes the combined or overall effect. (a) Myalgias. (b) Worsening diabetes/new-onset diabetes. (c) Gout. (d) Hyperuricemia. (e) Neurocognitive disorders. (f) Nasopharyngitis. (g) Urinary tract infection. (h) Upper respiratory infection. (i) Muscular disorders. (j) GFR decrease. BA, bempedoic acid; GFR, glomerular filtration rate.

Fig. 5

Risk of bias assessment of included studies using the Cochrane’s risk of bias tool 2.0.

Fig. 6

Funnel plots for visual assessment of publication bias. (a) LDL (ungrouped). (b) LDL (subgrouped). (c) TC (ungrouped). (d) TC (subgrouped). (e) Non-HDL (ungrouped). (f) Non-HDL (subgrouped). (g) HDL. (h) ApoB (ungrouped). (i) ApoB (subgrouped). (j) Triglycerides. (k) hsCRP (ungrouped). (l) hsCRP (subgrouped). (m) ACM. (n) MI. (o) Gout. (p) Hyperuricemia. (q) Muscular disorders. (r) Myalgias. (s) Coronary revascularization. (t) Noncoronary revascularization. (u) Hospitalization for heart failure. (v) Neurocognitive disorders. (w) Nasopharyngitis. (x) UTI. (y) URI. (z) Hospitalization for unstable angina. (aa) Stroke. (ab) Decrease in GFR. (ac) Worsening diabetes/hyperglycemia. (ad) Worsening diabetes/new onset diabetes. (ae) Cardiovascular-related mortality. (af) MACE. Apo B, abetalipoprotein B; ACM, all-cause mortality; BA, bempedoic acid; GFR, glomerular filtration rate; HDL-C, high-density lipoprotein- cholesterol; hsCRP, high-sensitivity C-reactive protein; LDL, low-density lipoprotein; MACE, major adverse cardiovascular events; MI, myocardial infarction; TC, total cholesterol; URI, upper respiratory tract infection; UTI, urinary tract infection.