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

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

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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
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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

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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.

Study Overview

• Status: Not yet recruiting
• Conditions: Cardiovascular
• Intervention / Treatment: Drug: Bempedoic Acid 180 MG Oral Tablet; Drug: Placebo; Drug: Rosuvastatin 5 mg

Detailed Description

Mechanism: Bempedoic acid works by inhibiting ACL in the cholesterol-synthesis pathway; since the activating enzyme is present only in the liver (not muscle), the risk of muscle-related side-effects is diminished.

Frontiers

Indication/Use Case: Particularly useful in patients who (a) are at elevated cardiovascular risk (primary prevention or secondary), (b) cannot tolerate statins or have suboptimal adherence, and (c) need further LDL-C reduction beyond statin (or in place of statin) therapy.

Efficacy:

~20-30% LDL-C lowering as monotherapy in statin-intolerant patients. PubMed

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Additional benefit when combined with other therapies (e.g., ~30-40% reduction when combined with ezetimibe).

medicinejournal.in

In primary-prevention high-risk patients intolerant of statins: LDL-C reduction ~21% and hs-CRP ~21% with meaningful reduction in cardiovascular events.

PubMed +1

Tolerability/Safety:

Lower risk of muscle symptoms compared to statins. PubMed

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Known adverse signals: hyperuricemia/gout, elevated liver enzymes, possibly increased creatinine/renal changes.

JAMA Network +1

Comparison with Statins:

Statins typically reduce LDL-C by much larger margins (30-50%+ depending on dose/intensity). Bempedoic acid's LDL-C reduction is more modest in comparison.

However, when looking at the risk reduction per unit LDL-C lowering, bempedoic acid appears to yield similar relative benefits as statins.

American College of Cardiology

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Clinical Implication: In patients with suboptimal statin use (due to intolerance, non-adherence, or contraindication), bempedoic acid offers a viable adjunct or alternative lipid-lowering strategy in the primary prevention setting.

Limitations:

Not a direct head-to-head trial of bempedoic acid versus statins in the scenario of suboptimal statin adherence.

Absolute reduction in LDL-C is lower than high-intensity statins, so expectations must be calibrated accordingly.

Long-term safety in wider populations continues to be monitored.

Cost and accessibility may vary by region; local cost-effectiveness needs evaluation.

• Study Type: Interventional
• Enrollment (Estimated): 690
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Sohaib Ashraf Consultant Cardiologist, MD Cardiology; Phone Number: +923334474523; Email: sohaib-ashraf@outlook.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

• 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.
• Willingness to provide written informed consent. Exclusion Criteria
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm A (Bempedoic acid); BA 180 mg once daily + placebo statin.	Drug: Bempedoic Acid 180 MG Oral Tablet; BA 180mg OD; Drug: Placebo; Placebo given OD
Placebo Comparator: Arm B (Statin); Rosuvastatin 5 mg once daily + placebo BA.	Drug: Placebo; Placebo given OD; Drug: Rosuvastatin 5 mg; rosuvastatin 5mg HS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute change in LDL-C	Absolute change in LDL-C from baseline to 6 months.	6 months
Proportion achieving LDL-C <100 mg/dL (or <70 mg/dL for diabetics).	Proportion achieving LDL-C <100 mg/dL (or <70 mg/dL for diabetics).	6 months
Change in hs-CRP	Change in hs-CRP from baseline.	6 months

Collaborators and Investigators

• Sponsor: Sohaib Ashraf

Study record dates

Study Major Dates

• Study Start (Estimated): November 10, 2025
• Primary Completion (Estimated): November 10, 2026
• Study Completion (Estimated): February 21, 2027

Study Registration Dates

• First Submitted: November 16, 2025
• First Submitted That Met QC Criteria: November 16, 2025
• First Posted (Actual): November 20, 2025

Study Record Updates

• Last Update Posted (Actual): November 20, 2025
• Last Update Submitted That Met QC Criteria: November 16, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: bempodoic acid
• Additional Relevant MeSH Terms: Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pharmaceutical Preparations; Dosage Forms; Hydrocarbons; Amides; Pyrimidines; Hydrocarbons, Halogenated; Sulfonamides; Sulfones; Fluorobenzenes; Hydrocarbons, Fluorinated; Rosuvastatin Calcium; 8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid; Tablets
• Other Study ID Numbers: RAIC PESSI/ESTT/2025/506

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No