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

Jan 22, 2024
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Author/Summarized by Author:
Anthony A. Bavry, MD,MPH,FACC
Trial Sponsor:
Esperion Therapeutics Inc.
Date Published:
01/17/2024
Date Updated:
01/22/2024
Original Posted Date:
07/05/2023
References

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.

Description:

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)

Interpretation:

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.

References:

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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