Lipid and anti-inflammatory effects of bempedoic acid across treatment regimens: A harmonized meta-analysis of randomized trials.

BACKGROUND

Bempedoic acid (BA) lowers low-density lipoprotein cholesterol (LDL-C) and high-sensitivity C-reactive protein (hs-CRP), but prior meta-analyses pooled heterogeneous timepoints and effect metrics, limiting precision and clinical interpretability. We conducted a harmonized meta-analysis using prespecified 12-week windows to generate consistent, clinically applicable estimates of BA's lipid and anti-inflammatory effects.

OBJECTIVE

To quantify the lipid-lowering and anti-inflammatory effects of BA using harmonized placebo-corrected percentage change estimates at prespecified 12-week timepoints and to evaluate whether treatment effects differ according to statin intolerance, background lipid-lowering therapy, or ezetimibe co-administration.

METHODS

PubMed, Scopus, and ClinicalTrials.gov were searched through November 2025 for randomized trials comparing BA monotherapy or fixed-dose BA-ezetimibe versus placebo. The primary endpoint was placebo-corrected percentage (PC%) change in LDL-C at 12 weeks; PC% change in hs-CRP was secondary. Multi-arm trials were pre-combined using inverse-variance weighting. Random-effects models used restricted maximum likelihood with Hartung-Knapp confidence intervals (CI), and prediction intervals (PI) were reported. Prespecified meta-regression evaluated diabetes prevalence, statin intolerance, background lipid-lowering therapy (LLT), ezetimibe co-administration, and timepoint.

RESULTS

Fourteen trials were included. BA monotherapy lowered LDL-C by -20.3 percentage points (pp) (95% CI -23.2 to -17.4), with consistent effects on background statin therapy (-18.3 pp; 95% CI -20.0 to -16.6). Statin-intolerant cohorts showed numerically larger LDL-C reductions (~25 pp), without statistically significant effect modification. Diabetes prevalence was not associated with differential LDL-C response in meta-regression. Fixed-dose BA-ezetimibe achieved a total -39.0 pp LDL-C reduction (95% CI -48.7 to -29.3); the pooled difference between monotherapy and fixed-dose combination estimates suggests an approximate 18 pp incremental reduction associated with ezetimibe co-administration. BA reduced hs-CRP by -23.1% (95% CI -32.7% to -13.6%), without augmentation by ezetimibe.

CONCLUSION

Across randomized trials, BA provides predictable LDL-C lowering that is consistent across LLT backgrounds and diabetes prevalence. Ezetimibe substantially augments LDL-C reduction but does not enhance hs-CRP lowering. These findings are consistent with an intrinsic anti-inflammatory effect of BA, although causality independent of LDL-C reduction cannot be definitively established from study-level data. These results refine BA's role within stepwise lipid-lowering strategies for patients who remain above LDL-C targets despite standard therapy.