What medications are used to treat elevated Lipoprotein(a) (Lp(a)) levels?

Medications for Elevated Lipoprotein(a) Levels

Niacin is currently the most recommended pharmacological treatment for reducing elevated Lipoprotein(a) levels, with reductions of 30-35% at doses up to 2000 mg/day. 1

Current Treatment Options

First-Line Pharmacological Therapy

• Niacin (nicotinic acid) is the most effective conventional medication for Lp(a) reduction, achieving 30-35% reductions at doses up to 2000 mg/day 1
• Niacin should be considered in high-risk patients with Lp(a) levels ≥50 mg/dL who have residual LDL-C elevations despite maximum statin therapy 2
• Extended-release or immediate-release formulations can be used, typically starting at lower doses (500 mg) and titrating up to minimize flushing side effects 3

Other Available Medications with Modest Effects

• Fibrates can reduce Lp(a) by up to 20%, with gemfibrozil showing the highest effect among this class 1
• PCSK9 inhibitors (evolocumab, alirocumab) reduce Lp(a) levels by 25-30% 4, 5
• Aspirin at low doses may provide modest (10-20%) reductions in Lp(a) levels 1
• L-Carnitine can reduce Lp(a) by 10-20% 1

Medications with Variable or Limited Effects

• Statins have inconsistent effects on Lp(a) and may actually increase levels in some patients 1
• Ezetimibe has shown variable effects on Lp(a) in different studies 3
• Hormone therapies (estrogens, testosterone) can reduce Lp(a) but are not recommended specifically for this purpose 1

Non-Pharmacological Approaches

Lipoprotein Apheresis

• LDL/Lp(a) apheresis is the most effective current treatment, reducing Lp(a) by up to 80% 1
• Should be considered for patients with progressive coronary heart disease despite maximum pharmacological therapy or with very high LDL-C levels (≥160-200 mg/dL) 2
• Has been shown to reduce cardiovascular disease risk in patients with elevated Lp(a) 1, 4

Emerging Therapies

Advanced Targeted Therapies in Development

• Antisense oligonucleotides (ASOs) targeting Lp(a) show the most promise with up to 90% reductions in Lp(a) levels 4, 5
• The Lp(a)HORIZON outcomes study is evaluating whether selective Lp(a) lowering with ASOs reduces cardiovascular events 4
• Other investigational approaches include small interfering RNAs (siRNAs) and microRNAs that regulate gene expression and protein production 5
• Mipomersen (an antisense oligonucleotide) reduces Lp(a) by 25-40% but has significant side effects limiting its use 5

Clinical Approach to Management

When to Measure Lp(a)

• Measure Lp(a) in patients with premature cardiovascular disease without evident risk factors 1, 6
• Consider measurement in patients with intermediate cardiovascular risk according to standard risk scores 1
• Test patients with recurrent or rapidly progressive vascular disease despite treatment 1
• Screen patients with familial hypercholesterolemia, genetic dyslipidemia, or low HDL-C 1

Treatment Algorithm

1. First optimize LDL-C with high-potency statins as the primary focus of lipid-modifying therapy 2
2. If Lp(a) ≥30-50 mg/dL with residual LDL-C elevations (≥70-100 mg/dL) despite maximum statin therapy, consider adding niacin up to 2 g/day 1, 2
3. For patients with progressive coronary disease despite optimal therapy, consider lipoprotein apheresis 2
4. Enroll eligible patients in clinical trials of targeted Lp(a)-lowering therapies when available 4, 5

Important Considerations and Caveats

• Lp(a) levels are primarily genetically determined and remain relatively constant throughout life 4
• Elevated Lp(a) (≥50 mg/dL) affects more than 20% of the global population but remains underdiagnosed 6, 4
• No currently available controlled studies have conclusively demonstrated that specifically lowering Lp(a) reduces cardiovascular risk 2
• The threshold for increased cardiovascular risk is generally accepted as >30-50 mg/dL or >75-125 nmol/L 6
• When measuring LDL-C in patients with elevated Lp(a), be aware that standard assays include the cholesterol content of Lp(a), potentially overestimating true LDL-C 1