Bempedoic Acid Versus Statins in Primary-Prevention Patients With Suboptimal Statin Adherence: Effects on LDL-C Reduction and Tolerability
Trial Snapshot
- Phase
- Phase 3
- Status
- Not yet recruiting
- Sponsor
- Sohaib Ashraf
- Enrollment
- 690
- Primary Endpoint
- Percentage change in LDL-C
Study Overview
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.
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
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 40 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Arm A (Bempedoic acid)
BA 180 mg once daily + placebo statin.
Intervention: Bempedoic Acid 180 MG Oral Tablet (Drug)
Arm A (Bempedoic acid)
BA 180 mg once daily + placebo statin.
Intervention: Placebo (Drug)
Arm B (Statin)
Rosuvastatin 5 mg once daily + placebo BA.
Intervention: Placebo (Drug)
Arm B (Statin)
Rosuvastatin 5 mg once daily + placebo BA.
Intervention: Rosuvastatin 5 mg (Drug)
Outcomes
Primary Outcomes
Percentage change in LDL-C
Time Frame: 6 months
Percentage change in LDL-C from baseline LDL-C
Composite adherence/tolerability endpoint:
Time Frame: 6 months
treatment discontinuation, muscle-related symptoms, or laboratory abnormalities (ALT/AST \>3× ULN, uric acid \>9 mg/dL).
Secondary Outcomes
- 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)
Investigators
Sohaib Ashraf
Consultant Cardiologist
Sheikh Zayed Federal Postgraduate Medical Institute