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June 12, 2025

Bempedoic Acid: The Statin Alternative for Lowering Cholesterol

Bempedoic acid is a cholesterol-lowering medication proven to reduce cardiovascular risk without common statin side effects. Here’s everything you need to know.

Bempedoic Acid: The Statin Alternative for Lowering Cholesterol

Bempedoic Acid: A New Era in Cholesterol-Lowering Therapy

Introduction

For decades, statins have dominated the cholesterol-lowering landscape. While effective, they’re not always well-tolerated—particularly among patients with muscle pain or liver enzyme concerns. Enter bempedoic acid, a new class of LDL-lowering medication that offers potent effects without activating in skeletal muscle, minimizing the risk of muscle-related side effects.

Approved by the FDA in 2020 and highlighted in the groundbreaking CLEAR Outcomes trial, bempedoic acid offers a promising alternative for individuals who can’t tolerate statins or who need additional LDL-C lowering despite existing therapy.

In this article, we’ll explore:

  • What bempedoic acid is and how it works

  • Who should consider using it

  • Key findings from the CLEAR Outcomes trial

  • Benefits and side effects

  • How it compares to statins and other therapies

  • Functional and integrative considerations

  • Scientific references to guide deeper learning

What Is Bempedoic Acid?

Bempedoic acid is an oral medication that lowers low-density lipoprotein cholesterol (LDL-C) by inhibiting cholesterol synthesis in the liver.

Mechanism of Action

  • Bempedoic acid inhibits ATP citrate lyase (ACL), an enzyme upstream of HMG-CoA reductase (which statins target).

  • This reduces cholesterol synthesis and upregulates LDL receptors, promoting LDL clearance from the bloodstream.

  • Uniquely, it is a prodrug activated only in the liver, not in skeletal muscle, making it ideal for patients with statin-associated muscle symptoms (SAMS).

Why Is Bempedoic Acid Important?

Cardiovascular disease (CVD) remains the leading cause of death worldwide. Lowering LDL-C is one of the most effective strategies to reduce risk.

Key Benefits of Bempedoic Acid:

  • Lowers LDL-C by 17–28% as monotherapy

  • No muscle activation → reduced myopathy risk

  • Well-tolerated alternative to statins

  • Oral formulation (vs. injectable PCSK9 inhibitors)

  • Now proven to reduce cardiovascular events in high-risk patients

Who Should Consider Bempedoic Acid?

1. Statin-Intolerant Patients

  • Especially those with muscle pain, cramps, or weakness not explained by other causes

  • Liver enzyme abnormalities due to statins

2. Patients Needing Additional LDL Lowering

  • Already on maximally tolerated statins but still above target

  • May be combined with ezetimibe, PCSK9 inhibitors, or lifestyle therapy

3. Individuals with ASCVD or High Cardiovascular Risk

  • Patients with prior heart attack, stroke, or stenting

  • Patients with diabetes, high Lp(a), or metabolic syndrome

Key Clinical Trials: The CLEAR Outcomes Study

📊 Trial Snapshot

  • Full Name: Cholesterol Lowering via Bempedoic Acid, an ACL-Inhibiting Regimen

  • Published: 2023 in New England Journal of Medicine

  • Design: Randomized, double-blind, placebo-controlled

  • Participants: 13,970 statin-intolerant patients with ASCVD or at high CV risk

  • Intervention: 180 mg/day bempedoic acid vs. placebo

  • Duration: Median follow-up of 40.6 months

🧠 Primary Endpoints:

Composite of:

  • Cardiovascular death

  • Nonfatal myocardial infarction (MI)

  • Nonfatal stroke

  • Coronary revascularization

🔍 Results

Outcome Placebo Bempedoic Acid Relative Risk Reduction
Primary endpoint 13.3% 11.7% 13%
Nonfatal MI 4.0% 3.2% 23%
Coronary revascularization 8.1% 6.7% 19%
Stroke No significant difference
CV death No significant difference

LDL-C was reduced by ~21% from baseline.
These results are remarkable, considering the patients were not using statins—yet still achieved meaningful event reduction.

Bempedoic Acid vs. Other Cholesterol-Lowering Therapies

Medication LDL-C Reduction Muscle Side Effects Route Use Case
Statins 30–50% Common (esp. in SAMS) Oral First-line therapy
Ezetimibe 13–20% Rare Oral Add-on or statin alternative
PCSK9 inhibitors 50–60% Rare Injectable High-risk, statin-intolerant
Bempedoic acid 17–28% Very rare Oral Ideal for statin intolerance
Omega-3 (EPA) 20–30% (TG), modest LDL effect Rare Oral Adjunct for inflammation and triglycerides

Side Effects of Bempedoic Acid

Bempedoic acid is generally well-tolerated but may have a few side effects to monitor:

Side Effect Frequency Notes
Elevated uric acid Mild increase Caution in gout patients
Muscle pain Rare Lower than with statins
Liver enzymes Occasional mild rise Monitor in liver disease
Tendon rupture Very rare Higher risk in >60, corticosteroid users
Upper respiratory symptoms Similar to placebo Self-limited

Functional and Integrative Considerations

While medications play an important role, addressing the root causes of dyslipidemia and vascular inflammation remains essential.

Combine Bempedoic Acid With:

🔹 Anti-inflammatory nutrition

  • Mediterranean or low-inflammatory diets

  • Reduce omega-6 seed oils

  • Eliminate processed sugars

🔹 Key Supplements

  • Omega 1300: EPA-rich omega-3 to lower inflammation and triglycerides

  • Curcumin Complex: Inhibits NF-κB and vascular inflammation

  • CoQ10 Omega: Supports mitochondrial health and endothelial function

  • AllerFx: Stabilizes mast cells, helpful in metabolic and vascular inflammation

  • B12 & Folate: Supports methylation and homocysteine regulation

🔹 Lifestyle Interventions

How to Use Bempedoic Acid

  • Standard Dose: 180 mg once daily

  • Can be taken with or without food

  • May be combined with ezetimibe (in a fixed-dose combo tablet) for added effect

  • May be used alongside PCSK9 inhibitors or omega-3s in high-risk patients

Limitations and Considerations

  • Not yet proven to reduce CV mortality (CV death reduction was not statistically significant)

  • Slower onset of LDL-lowering compared to PCSK9s

  • Not a substitute for lifestyle optimization—use in combination with anti-inflammatory strategies

  • Insurance coverage may vary but improving with guidelines

Clinical Case Example

Patient Profile:

  • 58-year-old female

  • Prior MI, cannot tolerate statins due to muscle pain

  • LDL-C: 148 mg/dL on ezetimibe

  • CRP: 4.2 mg/L

  • No access to PCSK9 therapy

Intervention:

Result at 3 Months:

  • LDL-C dropped to 102 mg/dL

  • CRP reduced to 2.1 mg/L

  • Patient tolerating therapy without myalgia

  • Better energy and reduced anxiety around statin side effects

Final Thoughts

Bempedoic acid represents a major advance in lipid-lowering therapy, especially for the millions of patients who struggle with statin intolerance or require additional LDL reduction.

It fills a critical gap:

  • Oral, once-daily dosing

  • No muscle activation

  • Effective in reducing major cardiovascular events (CLEAR Outcomes trial)

  • Ideal for real-world clinical use

Omega 1300 complements bempedoic acid by targeting vascular inflammation and improving lipid profiles—together offering a science-backed, integrative approach to cardiovascular risk reduction.

References

  1. Nissen SE, et al. Bempedoic Acid and Cardiovascular Outcomes in Statin-Intolerant Patients. NEJM. 2023.

  2. Ray KK, et al. Safety and Efficacy of Bempedoic Acid to Reduce LDL Cholesterol. NEJM. 2019.

  3. Tardif JC, et al. Effects of Bempedoic Acid on Major Adverse Cardiovascular Events. JAMA Cardiology. 2023.

  4. Nicholls SJ, et al. Role of Inflammation in Atherosclerosis. Nature Reviews Cardiology.

  5. Ballantyne CM, et al. Lipid Management in High-Risk Patients. American Heart Journal.