When Can a Statin and Bempedoic Acid Be Used Together?

The link between low-density lipoprotein cholesterol (LDL-C) and Atherosclerotic Cardiovascular Disease (ASCVD) is widely recognized as a cornerstone of modern preventive cardiology. While Statins remain the first-line defense, many patients in primary care struggle to reach their target LDL-C levels due to side effects or suboptimal response.

For GP Partners and Practice Managers, managing these “statin-intolerant” or high-risk patients often increases clinical pressure. However, the introduction of Bempedoic acid and the clarity provided by NICE guideline NG238 offers a vital pathway for combining therapies to achieve necessary cholesterol reduction.

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Key Takeaways:

• Targeted Synergy: Combining a statin with Bempedoic acid targets cholesterol synthesis at two points, providing substantial LDL-C reduction for high-risk patients.
• Liver-Specific Activation: Bempedoic acid is activated in the liver rather than muscle tissue, significantly reducing the risk of muscle-related side effects common with statins.
• Strict Dosage Limits: When used in combination, Simvastatin should not exceed 20mg and Pravastatin should not exceed 40mg to ensure patient safety.
• Standardised Monitoring: Ongoing safety requires regular lab tests for uric acid levels and renal profiles to manage the risk of hyperuricemia or gout.
• Specialist Guidance: According to NICE NG238, the initiation of Bempedoic acid should be led by a clinical expert, such as a cardiologist or lipid specialist.

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What is Bempedoic Acid and How does it Work?

Bempedoic acid is a first-in-class ATP-citrate lyase (ACLY) inhibitor. Unlike statins, which block HMG-CoA reductase throughout the body, Bempedoic acid is activated specifically in the liver.

Lipid management therapies continue to evolve as newer drugs become available for patients who do not achieve adequate cholesterol reduction with standard statin treatment alone.  Treatment now frequently incorporates non-statin medications such as ezetimibe and PCSK9 inhibitors to name a few. 

Among these options; Bempedoic Acid has generated a lot of interest, particularly in individuals who are intolerant to statin therapy.  However, there’s often uncertainty regarding the appropriate situations for combining statins with Bempedoic acid. 

Where Bempedoic Acid Fits in Current Lipid Guidelines?

Statins remain the cornerstone of Lipid lowering therapy. A large body of evidence supports their use in both primary and secondary prevention of CVD. Despite their excellent safety profile, statin associated muscle symptoms (SAMS) are a frequent cause of discontinuation in 7% to 10% of patients, leading to suboptimal LDL-C control. Several non statin therapies are used in patients intolerant to statins or patients requiring more substantial LDL-C reductions. 

According to NICE the Bempedoic acid is typically used in combination with other lipid lowering agents such as ezetimibe rather than the first line of treatment. Importantly, Bempedoic acid monotherapy is not currently part of NICE’s standard recommendation for primary prevention.

When LDL cholesterol targets are not achieved, clinicians follow NICE recommendations:

• Start with a statin (often Atorvastatin as the first line).
• If cholesterol targets are not met, add Ezetimibe.
• Additional therapies such as Bempedoic acid are considered in specific cases.

When to Consider the Combination (NICE NG238 Criteria)?

According to NICE guideline NG238, combining these therapies is appropriate in specific clinical scenarios:

• Suboptimal Statin Response: When a patient is on the maximum tolerated dose of a statin but has not achieved a 40% or greater reduction in non-HDL cholesterol.
• Statin Intolerance: For patients who can only tolerate low-intensity statins, Bempedoic acid can be added to “bridge the gap” to their target LDL-C levels.
• Contraindications: If Ezetimibe is not tolerated or is insufficient on its own, Bempedoic acid serves as the next evidence-based step in lipid-lowering therapy.

Critical Safety Measures and Dose Limitations

While the combination is effective, clinicians must manage drug-drug interactions carefully. Bempedoic acid can increase the plasma concentration of certain statins, raising the risk of myopathy. The following cases should be considered:

• Simvastatin: Dosage should not exceed 20mg daily when used with Bempedoic acid.
• Pravastatin: Dosage should not exceed 40mg daily when used in this combination.
• Specialist Initiation: NICE recommends that the decision to start Bempedoic acid be made by a clinical expert, such as a cardiologist or a lipid specialist.

Specialist-Led Decision Making/ Prescribing 

As stated in the NICE GUIDELINES NG238 , the decision to start Bempedoic acid should be taken by a clinical expert. It is not routinely started in primary care, caution and safety measures should be taken and it should only be started by

• A cardiologist
• Lipid specialist
• Clinician with expertise in complex lipid management

Monitoring for Patient Safety

To ensure long-term success, practices should implement a standardized monitoring protocol for patients on this dual therapy:

• Uric Acid Levels: Bempedoic acid can inhibit renal transporters, leading to hyperuricemia and an increased risk of gout.
• Liver & Renal Function: Periodic LFTs and renal profiles are essential, particularly within the first few months of treatment.
• Tendon Health: Though rare, there is a risk of tendon rupture; patients over 60 or those with a history of tendon injury require closer observation.

Conclusion

The combination of a statin and Bempedoic acid represents a significant advancement in managing high-risk ASCVD patients who struggle to reach their LDL-C targets. By adhering to the NICE NG238 criteria and maintaining awareness of essential safety protocols, practices can effectively close the treatment gap for statin-intolerant individuals.

Ultimately, the goal of these therapies is to reduce cardiovascular risk and improve long term patient health outcomes without compromising clinical capacity. Managing these complex prescribing pathways and the necessary safety monitoring can be resource-intensive for any GP practice. The Medicines Management Team (TMMT) offers a readymade, structured solution to integrate specialist pharmacy support into your practice via the NHS ARRS scheme.

Explore how TMMT’s medicines management service can streamline your practice’s clinical workload. Contact us today to learn more.

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