Impact of Bempedoic Acid on Lipoprotein(a)
Bempedoic acid has minimal to no significant effect on lipoprotein(a) [Lp(a)] levels, despite its established efficacy in lowering LDL cholesterol and reducing inflammatory markers. 1
Mechanism and Primary Effects of Bempedoic Acid
Bempedoic acid is a novel LDL cholesterol-lowering agent that works by inhibiting ATP-citrate lyase (ACL), an enzyme upstream of HMG-CoA reductase in the cholesterol biosynthesis pathway. This mechanism:
- Results in decreased hepatic cholesterol synthesis and upregulation of LDL receptors 2
- Is liver-selective due to the activating enzyme ACSVL1 being expressed primarily in the liver 2
- Avoids muscle-related side effects common with statins 2, 3
Effects on Lipid Parameters
Bempedoic acid has well-documented effects on several lipid parameters:
- Reduces LDL cholesterol by approximately 15-25% when added to maximally tolerated statin therapy 4, 2
- Provides up to 38% additional LDL-C reduction when combined with ezetimibe 4, 2
- Significantly lowers non-HDL cholesterol, total cholesterol, and apolipoprotein B 1, 5
- Reduces high-sensitivity C-reactive protein (hs-CRP) by approximately 24.3% 1, 6
Effect on Lipoprotein(a)
Despite its beneficial effects on other lipid parameters and inflammatory markers:
- Bempedoic acid has minimal effect on lipoprotein(a) levels 1
- Current guidelines and research do not indicate that bempedoic acid significantly impacts Lp(a) 4, 2
- The 2024 research specifically notes that while bempedoic acid reduces LDL-C, hs-CRP, and other inflammatory markers, it has minimal effect on Lp(a) levels 1
Clinical Implications
For patients with elevated Lp(a) levels:
- Bempedoic acid should not be considered as a primary therapy for Lp(a) reduction
- Other therapeutic approaches may be needed for patients with elevated Lp(a) as a cardiovascular risk factor
- Bempedoic acid remains valuable for its LDL-C lowering effects, particularly in statin-intolerant patients 3, 6
Cardiovascular Outcomes
The CLEAR Outcomes trial demonstrated that bempedoic acid:
- Reduced the composite outcome of four-point major adverse cardiovascular events by 13% compared with placebo 4
- Showed greater benefit in primary prevention (30% reduction) compared to secondary prevention 4
- Provided a 17% reduction in major adverse cardiovascular events in patients with diabetes 4
Important Considerations
When prescribing bempedoic acid, clinicians should be aware that:
- It is indicated as an adjunct to diet and maximally tolerated statin therapy for adults with heterozygous familial hypercholesterolemia or established ASCVD requiring additional LDL-C lowering 4, 2
- It may be particularly valuable for statin-intolerant patients 3, 6
- Monitoring for potential side effects including elevated uric acid levels and tendon disorders is recommended 2
In summary, while bempedoic acid is an effective agent for LDL-C reduction and cardiovascular risk reduction, current evidence indicates it has minimal impact on lipoprotein(a) levels.