ConsensusLab

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Metabolic & Cardiometabolic

bempedoic acid decreases LDL cholesterol (~20-25%)

In plain terms: Does bempedoic acid lower LDL cholesterol, and by how much?

Strong support Metabolic & Cardiometabolic

Part of: 💊 bempedoic acid

RefutedContestedStrong support
consensus score 1.00

Yes — consistently ~15-25% LDL-C reduction (≈17-18% on a statin background, ~21-28% as monotherapy/statin-intolerant; ~38% with ezetimibe), proven across the CLEAR phase 3 program and multiple meta-analyses.

📅 Last reviewed: 2026-07-15 ⓘ

Evidence ladder

How far up the ladder this claim has climbed. A high consensus on a low rung means "consistent so far," not "proven in people."

Top evidence so far: All trials, pooled (Meta-analysis)

MechanismIn-vitroAnimalObservationalRCTMeta-analysis

How the studies fall

15 support 0 contradict 0 tested null 0 mixed · 15 sources, 15 independent groups · 4 superseded — pooled inside a review, counted once

The evidence (19)

SourceGradeStanceQualityFinding
Giammanco A et al
2026 · Giornale italiano di cardiologia		 observational supports high European prospective observational study (MILOS), Italian cohort n=855 with 8-week follow-up LDL-C data; mean LDL-C reduction 22.6% (median 25.4%) with bempedoic acid alone or + ezetimibe FDC.
Zhao
2020 · BMC Pharmacol Toxicol		 meta-analysis supports moderate Meta-analysis (mono and combination): bempedoic acid significantly lowered LDL-C alone and additively with statins/ezetimibe.
Yamashita
2025 · Circ J		 RCT supports moderate CLEAR-J (Japanese phase 3): bempedoic acid significantly lowered LDL-C vs placebo, replicating Western trials in a distinct population.
Ray
2019 · N Engl J Med		 RCT supports high CLEAR Harmony (n=2230, on max-tolerated statin): LDL-C -16.5% from baseline, placebo-corrected -18.1 percentage points at wk 12.
↩ SUPERSEDED — pooled in the review above, counted once
Laufs
2019 · J Am Heart Assoc		 RCT supports high CLEAR Serenity (n=345 statin-intolerant): LDL-C placebo-corrected -21.4% at wk 12; well tolerated, myalgia not increased vs placebo.
↩ SUPERSEDED — pooled in the review above, counted once
Ballantyne
2018 · Atherosclerosis		 RCT supports moderate CLEAR Tranquility (n=269 statin-intolerant, on ezetimibe): bempedoic acid added to ezetimibe lowered LDL-C ~-23.5% placebo-corrected (combo ~38% total).
↩ SUPERSEDED — pooled in the review above, counted once
Heikal M et al
2026 · study_type: animal		 animal supports low Pharmaceutical formulation study developing a bempedoic acid-ezetimibe fixed-dose tablet; in vivo animal model showed the optimized formulation significantly reduced serum LDL (alongside TC and TG) versus reference product.
Nissen
2023 · N Engl J Med		 RCT supports high CLEAR Outcomes (n=13,970 statin-intolerant): bempedoic acid cut LDL-C ~21% vs placebo at 6 mo (baseline 139 mg/dL), durable over trial.
Ballantyne
2022 · Am J Cardiol		 RCT supports moderate CLEAR Harmony open-label extension: LDL-C and hsCRP reductions sustained through up to 2.5 years of continuous treatment.
Hsieh IC et al
2026 · study_type: observational		 observational supports moderate Pragmatic phase 4 trial (CLEAR Taiwan), n=180 hypercholesterolemia patients on bempedoic acid add-on for 12 weeks; median LDL-C change -19% (117.5 to 92 mg/dL, p<0.01), 31.3% reached LDL-C targets.
Ridker
2023 · J Clin Lipidol		 RCT supports high CLEAR Harmony biomarker substudy (n=817): LDL-C -21.1% placebo-corrected; pattern of lipid+inflammation lowering near-identical to statins.
Khattak S et al
2025 · study_type: observational		 observational supports moderate Observational study (n=256, including small bempedoic acid subgroup) comparing novel lipid-lowering therapies; bempedoic acid associated with 36% LDL-C reduction at 12 months, less than PCSK9i/inclisiran.
Nelson J et al
2026 · study_type: observational		 observational supports high Real-world EHR cohort (Veradigm), n=900 bempedoic acid alone / n=615 + ezetimibe; by 3 months median LDL-C reduction 21% (BA alone) and 33% (BA+EZE), sustained to 12 months.
Masuda D et al
2026 · study_type: RCT		 observational supports moderate Phase 3 long-term single-arm study (CLEAR-J LONG), n=130 Japanese patients, bempedoic acid 180mg/day for 52 weeks; LDL-C decreased 21.6% overall (25.3% in newly enrolled subgroup), well tolerated.
Venkatraman
2023 · Eur J Clin Pharmacol		 meta-analysis supports moderate Systematic review/meta-analysis: bempedoic acid consistently and significantly reduced LDL-C across lipid-lowering indications.
Uddin
2023 · Curr Probl Cardiol		 meta-analysis supports high 7 RCTs (n=17,816): LDL-C mean difference -22.4% (95% CI -25.9 to -18.8) vs placebo; total cholesterol -13.9%.
De Filippo
2023 · Cardiovasc Diabetol		 meta-analysis supports high Meta-analysis of RCTs: bempedoic acid significantly reduced LDL-C and other atherogenic lipids vs placebo across populations.
Goldberg
2019 · JAMA		 RCT supports high CLEAR Wisdom (n=779, on max-tolerated statin): LDL-C placebo-corrected -17.4% at wk 12; also lowered non-HDL-C, ApoB, hsCRP.
↩ SUPERSEDED — pooled in the review above, counted once
Feingold KR.
2000 · MDText.com, Inc., South Dartmouth (MA)		 observational supports low Endotext narrative review states bempedoic acid lowers LDL-C by 15-25% via hepatic ATP citrate lyase inhibition and LDL receptor upregulation; mono or add-on not specified beyond general mechanism.

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