Bempedoic Acid Versus Statins in Primary-Prevention Patients With Suboptimal Statin Adherence: Effects on LDL-C Reduction and Tolerability

NCT07239414 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: RAIC PESSI/ESTT/2025/506
• Study Type: interventional
• Target: 690
• Locations: 0 countries
• Sites: N/A

Brief Summary

Bempedoic acid is an oral, non-statin LDL-cholesterol (LDL-C) lowering agent that inhibits ATP citrate lyase (ACL), upstream of HMG-CoA reductase (the enzyme inhibited by statins). MDPI +1 In patients with hypercholesterolemia who are unable to tolerate statins, or have sub-optimal statin adherence/tolerance, bempedoic acid has been shown to reduce LDL-C by \~20-30% (monotherapy) and more when added to other therapies (e.g., ezetimibe) (≈30-40%). PubMed

• 2 medicinejournal.in
• 2 In the large primary-prevention subgroup of the trial CLEAR Outcomes (statin-intolerant patients without prior cardiovascular event), bempedoic acid (180 mg daily) lowered LDL-C by \~21.3% and hs-CRP by \~21.5%. It also was associated with a significant reduction in major adverse cardiovascular events (MACE): hazard ratio 0.70 (95% CI 0.55-0.89) versus placebo over \~40 months. PubMed +1 Regarding tolerability: muscle-related adverse events appear lower compared to statins (because bempedoic acid is activated only in the liver, not in skeletal muscle) and it appears generally well tolerated, but there are signals of increased uric acid/gout, elevated hepatic enzymes, and creatinine/renal effects. MDPI +1 Comparative cardiovascular benefit (when normalized per unit LDL-C reduction) suggests that bempedoic acid may yield similar relative risk reductions as statins, though absolute LDL-C lowering is less.

Conditions

Cardiovascular

Keywords

bempodoic acid

Outcome Measures

Primary Outcomes (2)

• Percentage change in LDL-C

  Percentage change in LDL-C from baseline LDL-C

  6 months

• Composite adherence/tolerability endpoint:

  treatment discontinuation, muscle-related symptoms, or laboratory abnormalities (ALT/AST \>3× ULN, uric acid \>9 mg/dL).

  6 months

Secondary Outcomes (3)

• Absolute change in LDL-C

  6 months

• Proportion achieving LDL-C <100 mg/dL (or <70 mg/dL for diabetics).

  6 months

• Change in hs-CRP

  6 months

Study Arms (2)

Arm A (Bempedoic acid)

ACTIVE COMPARATOR

BA 180 mg once daily + placebo statin.

Drug: Bempedoic Acid 180 MG Oral Tablet; Drug: Placebo

Arm B (Statin)

PLACEBO COMPARATOR

Rosuvastatin 5 mg once daily + placebo BA.

Drug: Rosuvastatin 5 mg; Drug: Placebo

Interventions

Bempedoic Acid 180 MG Oral Tablet DRUG

BA 180mg OD

Arm A (Bempedoic acid)

Rosuvastatin 5 mg DRUG

rosuvastatin 5mg HS

Arm B (Statin)

Placebo DRUG

Placebo given OD

Arm A (Bempedoic acid); Arm B (Statin)

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults aged ≥40 years with no established ASCVD (no prior myocardial infarction, stroke, or acute coronary syndrome).
• Indicated for lipid-lowering therapy (LDL-C ≥130 mg/dL or 10-year ASCVD risk
• ≥7.5%).
• Documented history of poor statin adherence, defined as:
• Self-reported adherence \<80% in the past 3 months, or
• Prior statin discontinuation for adverse effects documented in the medical record.

You may not qualify if:

• Established ASCVD (secondary prevention).
• Severe hepatic impairment (ALT or AST \>3× upper limit of normal).
• Severe renal impairment (eGFR \<30 mL/min/1.73 m²).
• Pregnancy, breastfeeding, or women of childbearing potential not using contraception.
• Current or planned treatment with PCSK9 inhibitors, fibrates, or niacin.
• Known hypersensitivity to study drugs or excipients.

Sponsors & Collaborators

• Sohaib Ashraf: lead

MeSH Terms

Interventions

8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid; Tablets; Rosuvastatin Calcium

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations; Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Central Study Contacts

Sohaib Ashraf Consultant Cardiologist, MD Cardiology

CONTACT

+923334474523; sohaib-ashraf@outlook.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Consultant Cardiologist

Study Record Dates

• First Submitted: November 16, 2025
• First Posted: November 20, 2025
• Study Start: November 10, 2025
• Primary Completion (Estimated): November 10, 2026
• Study Completion (Estimated): February 21, 2027
• Last Updated: November 20, 2025

Record last verified: 2025-11