Metabolic & Cardiometabolic
bempedoic acid decreases major adverse cardiovascular events
In plain terms: Does bempedoic acid reduce major adverse cardiovascular events (MACE)?
Strong support Metabolic & Cardiometabolic 🔬 Includes disconfirming
Part of: 💊 bempedoic acid
RefutedContestedStrong support
consensus score 0.91
Yes — CLEAR Outcomes (the sole large CV outcomes RCT) showed a 13% relative reduction in 4-point MACE in statin-intolerant high-risk patients, confirmed by meta-analyses; driven by MI and revascularization, with no reduction in CV or all-cause death.
📅 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
19 support 0 contradict 1 tested null 1 mixed · 21 sources, 18 independent groups
The evidence (21)
| Source | Grade | Stance | Quality | Finding |
|---|---|---|---|---|
| Nissen 2023 · N Engl J Med | RCT | supports | high | CLEAR Outcomes (n=13,970): primary 4-pt MACE HR 0.87 (95% CI 0.79-0.96), 13% relative reduction over median 40.6 mo; MI -23%, coronary revasc -19%. |
| Rhabneh L et al 2026 · study_type: observational | observational | supports | moderate | Retrospective TriNetX cohort, n=6,549 matched pairs with established CAD (secondary prevention); MACE occurred in 5.7% (atorvastatin alone) vs 3.2% (atorvastatin+bempedoic acid), HR 1.606 (95% CI 1.302-1.980, P<0.001) favoring the combinati |
| Zhao X et al 2026 · study_type: meta-analysis | meta-analysis | supports | high | Frequentist network meta-analysis of 18 RCTs (89,717 diabetic participants, 14 lipid-modifying agents); found statins, ezetimibe, PCSK9i and bempedoic acid each reduced MACE risk, with agent-specific profiles (no bempedoic acid-specific poo |
| Bays 2025 · J Am Heart Assoc | RCT | supports | moderate | CLEAR Outcomes obesity subset: MACE reduction consistent across BMI categories. |
| Patel J et al 2026 · study_type: observational | observational | supports | low | Narrative review of novel lipid-lowering approaches stating 'CLEAR Outcomes showed fewer major cardiovascular events in statin-intolerant populations' with bempedoic acid via ACL inhibition, no new HR/CI presented. |
| Myerson M et al 2025 · study_type: observational | observational | supports | low | Narrative review of nonstatin LDL-C-lowering options stating ezetimibe, bempedoic acid, or PCSK9 inhibitors added to statin therapy 'can lead to additional lowering of LDL-C and beneficial reductions in cardiovascular events'; no bempedoic |
| Lincoff 2024 · J Am Coll Cardiol | RCT | supports | high | 13% MACE reduction per ~21% LDL drop is consistent with the per-mmol/L benefit seen with statins (CTT collaboration), supporting LDL-mediated effect. |
| Nissen 2023 · JAMA | RCT | supports | high | CLEAR Outcomes primary-prevention subgroup (n=4206): MACE HR 0.70 (0.55-0.89), benefit extends to patients without prior CV event. |
| Menon 2026 · J Clin Lipidol | RCT | supports | moderate | Post hoc: CV benefit of bempedoic acid persisted regardless of adjunctive lipid-modifying therapy, arguing the effect is drug-attributable. |
| Uddin 2023 · Curr Probl Cardiol | meta-analysis | supports | high | 7 RCTs (n=17,816): MACE RR 0.87 (0.80-0.94); nonfatal MI RR 0.73; unstable-angina hospitalization RR 0.69; revascularization RR 0.82. |
| Abdullah M et al 2025 · study_type: observational | observational | supports | low | Narrative review 'Indications of Bempedoic Acid' stating RCTs show 15-20% LDL-C reductions monotherapy 'alongside cardiovascular event reduction in statin-intolerant patients'; no numeric MACE HR/CI in abstract. |
| Cho 2024 · Circulation | RCT | supports | moderate | CLEAR Outcomes by sex: CV benefit consistent in women and men; treatment effect not modified by sex. |
| Mancini GBJ et al 2026 · study_type: RCT | RCT | supports | moderate | Post hoc analysis of phase 3 studies (max-statins pool n=3009; statin-intolerant/CLEAR Outcomes pool n=13,970) stratified by age; reports LDL-C reductions were consistent across ages and states 'cardiovascular event reduction was statistica |
| Sayed 2023 · Cardiovasc Drugs Ther | meta-analysis | supports | high | Meta-analysis: bempedoic acid reduced MACE and nonfatal MI; no significant effect on CV or all-cause mortality. |
| Yarrarapu 2024 · J Cardiol | observational | mixed | moderate | Review: CLEAR Outcomes established CV benefit, but notes current evidence does NOT show a reduction in cardiovascular deaths. |
| Colivicchi F et al 2025 · study_type: observational | observational | supports | low | Italian-language narrative review of CLEAR Outcomes and its subgroup analyses, confirming LDL-C lowering 'translates into a significant decrease in major adverse cardiovascular events,' consistent in both primary prevention and recurrent-ev |
| Wang 2020 · Cardiovasc Diabetol | meta-analysis | supports | low | Early meta-analysis (pre-outcomes): insufficient evidence to confirm CV event reduction; flagged need for a dedicated outcomes trial. |
| Lin 2022 · BMJ Open | meta-analysis | tested-null | moderate | Pre-CLEAR-Outcomes meta-analysis: trends toward fewer CV events but no statistically significant MACE reduction with then-available data — benefit unproven until the outcomes trial. |
| Nicholls 2024 · JAMA Cardiol | RCT | supports | high | Prespecified total-events analysis: bempedoic acid reduced total (first+recurrent) CV events HR 0.80 (0.72-0.89), reinforcing first-event finding. |
| Katzmann JL et al 2026 · study_type: observational | observational | supports | low | Narrative review on sequencing non-statin therapies stating bempedoic acid (with statins, ezetimibe, PCSK9 antibodies) has 'proven cardiovascular benefit'; no trial-level HR/CI given. |
| Colivicchi F et al 2026 · study_type: observational | observational | supports | low | Viewpoint/narrative discussion (not a systematic review) stating RCTs 'have shown bempedoic acid efficacy in...reducing...major cardiovascular adverse events,' citing this as basis for ESC guideline inclusion. |
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