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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 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 ReductionPrimary 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. 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 NotesElevated 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 🔹 Key Supplements 🔹 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 ThoughtsBempedoic 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
Nissen SE, et al. Bempedoic Acid and Cardiovascular Outcomes in Statin-Intolerant Patients. NEJM. 2023.
Ray KK, et al. Safety and Efficacy of Bempedoic Acid to Reduce LDL Cholesterol. NEJM. 2019.
Tardif JC, et al. Effects of Bempedoic Acid on Major Adverse Cardiovascular Events. JAMA Cardiology. 2023.
Nicholls SJ, et al. Role of Inflammation in Atherosclerosis. Nature Reviews Cardiology.
Ballantyne CM, et al. Lipid Management in High-Risk Patients. American Heart Journal. (责任编辑：) |