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

Medications for Lowering Lipoprotein(a) Levels

Niacin (immediate or extended-release formulation) up to 2000 mg/day is the most recommended medication for Lp(a) reduction, providing 30-35% reduction in levels, optimally used in conjunction with glycemic and LDL control. 1

Current Therapeutic Options for Lp(a) Reduction

First-Line Therapy

• Niacin (Nicotinic Acid)
  • Dosage: Up to 2000 mg/day (immediate or extended-release)
  • Efficacy: 30-35% reduction in Lp(a) levels
  • Best used alongside glycemic control and LDL management
  • Side effects include flushing, which can be mitigated by gradual dose titration

Second-Line Options

• Fibrates

  • Efficacy: Up to 20% reduction in Lp(a)
  • Gemfibrozil shows the highest effect among fibrates
  • Consider in patients who cannot tolerate niacin

• PCSK9 Inhibitors

  • Efficacy: 25-30% reduction in Lp(a) levels
  • Not FDA-approved specifically for Lp(a) reduction but may provide benefit as part of comprehensive lipid management

• Aspirin (Acetylsalicylic Acid)

  • Efficacy: 10-20% reduction
  • Effective even at low doses
  • Consider as adjunctive therapy

Other Agents with Modest Effects

• L-Carnitine

  • Efficacy: 10-20% reduction
  • Mechanism: Mitochondrial fatty acid transporter

• Hormone Therapies (in specific populations)

  • Estrogens: 37% reduction (post-menopausal women)
  • Testosterone: 30-40% reduction
  • Tamoxifen: 35% reduction
  • Tibolone: 35% reduction
  • Raloxifene: 18% reduction

Last Resort Option

• LDL/Lp(a) Apheresis
  • Efficacy: Up to 80% reduction
  • Has been shown to reduce cardiovascular disease risk
  • Reserved for patients with very high Lp(a) levels and progressive cardiovascular disease despite optimal therapy

Clinical Approach to Lp(a) Management

When to Measure Lp(a)

Measure Lp(a) in patients with:

1. Premature cardiovascular disease without evident risk factors
2. Intermediate cardiovascular risk according to standard risk scores
3. Recurrent or rapidly progressive vascular disease despite treatment
4. Familial hypercholesterolemia or genetic dyslipidemia
5. Family history of premature cardiovascular events or known high Lp(a) 1, 2

Treatment Algorithm

1. Establish baseline Lp(a) level

   • Significant risk threshold: >50 mg/dL (~100-125 nmol/L)
   • Traditional threshold: >30 mg/dL

2. For patients with elevated Lp(a):

   • Start with aggressive management of other modifiable risk factors
   • Target lower LDL-C levels than standard targets
   • Consider niacin up to 2000 mg/day as the primary Lp(a)-lowering agent
   • Monitor for side effects and adjust dosing accordingly

3. If niacin is not tolerated or contraindicated:

   • Consider fibrates (preferably gemfibrozil)
   • Add low-dose aspirin if not contraindicated

4. For patients with progressive disease despite optimal therapy:

   • Consider referral for LDL/Lp(a) apheresis
   • Evaluate eligibility for clinical trials of emerging therapies

Emerging Therapies

Several promising treatments are in development:

• Antisense oligonucleotides (e.g., mipomersen, pelacarsen): Reduce Lp(a) by up to 40-90%
• Small interfering RNAs (e.g., olpasiran): Can reduce Lp(a) by >80%
• PCSK9 inhibitors: Already available but with modest Lp(a)-lowering effects
• MTP inhibitors (e.g., lomitapide): Show promise but mechanism of action on Lp(a) is poorly understood 1, 3

Important Caveats and Considerations

• Statins have inconsistent effects on Lp(a) and may even cause significant elevation in some patients 1
• Lifestyle modifications have minimal effect on Lp(a) levels, unlike other lipid parameters 2
• Standard "LDL-C" measurements include Lp(a) cholesterol content, which can mask residual risk 2
• There is no universally accepted treatment goal for Lp(a) levels, but reduction is associated with decreased cardiovascular risk 1
• Consider more aggressive LDL-C targets in patients with elevated Lp(a) to address overall cardiovascular risk 2

By implementing this structured approach to Lp(a) management, clinicians can effectively address this important component of residual cardiovascular risk and potentially improve morbidity and mortality outcomes in high-risk patients.