Cholesterol Lowering via Bempedoic Acid, an ACL-Inhibiting Regimen - CLEAR Outcomes

Contribution To Literature:

Highlighted text has been updated as of January 22, 2024.

The CLEAR Outcomes trial showed that bempedoic acid reduces major adverse cardiovascular events.


The goal of the trial was to evaluate bempedoic acid compared with placebo among statin-intolerant patients.

Study Design

  • Randomized
  • Parallel
  • Placebo

Statin-intolerant patients were randomized to bempedoic acid 180 mg daily (n = 2,100) vs. placebo (n = 2,106).

  • Total number of enrollees: 13,970, including 4,206 primary prevention patients
  • Duration of follow-up: median 40 months
  • Mean patient age: 68 years
  • Percentage female: 59%
  • Percentage with diabetes: 65%

Inclusion criteria:

  • Subjects 18-85 years of age
  • Low-density lipoprotein (LDL) cholesterol ≥100 mg/dL
  • Statin-intolerance
  • High cardiovascular risk (elevated Reynolds or SCORE risk score), coronary artery calcium >400 Agatson units, or diabetes (in men >60 years of age and in women >65 years of age)

Exclusion criteria:

  • Fasting blood triglycerides >500 mg/dL (5.6 mmol/L) at screening
  • Recent (within 90 days of screening) history of major cardiovascular events, transient ischemic attack, or unstable or symptomatic cardiac arrhythmia
  • History of severe heart failure
  • Uncontrolled hypertension or uncontrolled diabetes

Principal Findings:

The primary outcome of cardiovascular death, myocardial infarction, stroke, or coronary revascularization occurred in 5.3% of the bempedoic acid group vs. 7.6% in the placebo group (p = 0.002).

Secondary outcomes:

  • Cardiovascular death, myocardial infarction, or stroke: 4.0% in the bempedoic acid group vs. 6.4% in the placebo group (p < 0.01)
  • Change in LDL cholesterol from baseline to 6 months: -34 mg/dL in the bempedoic acid group vs. -3.8 mg/dL (p < 0.05)
  • Serious adverse events were similar between treatment groups
  • Total number of major adverse cardiovascular events (cardiovascular death, myocardial infarction, stroke, or coronary revascularization): 11.7% with bempedoic acid vs. 13.3% with placebo (p = 0.004)


Among statin-intolerant patients with increased cardiovascular risk, bempedoic acid improves outcomes. Bempedoic acid versus placebo significantly reduced LDL cholesterol and was associated with a reduction in adverse cardiovascular events. Bempedoic acid versus placebo was also associated with a reduction in hard outcomes (cardiovascular death, myocardial infarction, or stroke). A limitation is that this was a secondary analysis of a subpopulation in a larger randomized trial.


Nicholls SJ, Nelson AJ, Lincoff M, et al. Impact of Bempedoic Acid on Total Cardiovascular Events: A Prespecified Analysis of the CLEAR Outcomes Randomized Clinical Trial. JAMA Cardiol 2024;Jan 17:[Epub ahead of print].

Nissen SE, Menon V, Nicholls SJ, et al. Bempedoic Acid for Primary Prevention of Cardiovascular Events in Statin-Intolerant Patients. JAMA 2023;330:131-40.

Editorial: Kazi DS. Bempedoic Acid for High-Risk Primary Prevention of Cardiovascular Disease: Not a Statin Substitute but a Good Plan B. JAMA 2023;330:123-5.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Lipid Metabolism, Nonstatins, Prevention

Keywords: Cholesterol, LDL, Dyslipidemias

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