What is the treatment approach for patients with elevated lipoprotein(a) (Lp(a)) levels?

Treatment Approach for Elevated Lipoprotein(a)

For patients with elevated lipoprotein(a) [Lp(a)] levels, aggressive LDL-cholesterol reduction is the primary management strategy, with niacin being the most effective conventional medication specifically for Lp(a) reduction. 1, 2

When to Measure Lp(a)

• Measure Lp(a) in patients with premature cardiovascular disease without evident risk factors 1, 2
• Consider measurement in patients with intermediate cardiovascular risk according to standard risk scores 2
• Test patients with recurrent or rapidly progressive vascular disease despite treatment 2
• Screen patients with familial hypercholesterolemia, genetic dyslipidemia, or low HDL-C 2
• Consider testing in patients with a family history of premature cardiovascular disease 2

Interpreting Lp(a) Levels

• Traditional thresholds for elevated Lp(a) are >30 mg/dL or >75 nmol/L (approximately the 75th percentile in white populations) 2
• European guidelines define significant risk at Lp(a) >50 mg/dL (approximately 100-125 nmol/L) 2
• Risk increases progressively with higher Lp(a) levels, with particularly high risk at >100 mg/dL 2
• Elevated Lp(a) (≥50 mg/dL) affects more than 20% of the global population but remains underdiagnosed 1

Treatment Algorithm

First-Line Approach

• Aggressively reduce LDL-cholesterol as the primary management strategy 2
• Set lower LDL-C goals for patients with elevated Lp(a) 2
• Be aware that standard LDL-C assays include the cholesterol content of Lp(a), potentially overestimating true LDL-C 1, 2

Specific Lp(a)-Lowering Medications

• 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, 3
• Consider niacin (immediate- or extended-release formulation) up to 2000 mg/day for reduction of Lp(a) levels, optimally in conjunction with glycemic control and LDL control 3
• Fibrates can reduce Lp(a) by up to 20%, with gemfibrozil showing the highest effect among this class 1
• Low-dose aspirin may provide modest (10-20%) reductions in Lp(a) levels 1
• L-Carnitine can reduce Lp(a) by 10-20% 1

Medications with Neutral or Negative Effects on Lp(a)

• Statins have inconsistent effects on Lp(a) and may actually increase levels in some patients 1, 2
• Ezetimibe may also increase Lp(a) levels 2

Advanced Therapies

• PCSK9 inhibitors reduce Lp(a) by approximately 25-30%, which is about half of their effect on LDL-C reduction (59%) 3, 4
• LDL/Lp(a) apheresis is the most effective current treatment, reducing Lp(a) by up to 80% 1, 2
  • Consider in patients with elevated Lp(a) >60 mg/dL, controlled LDL-C, and recurrent events or progression of CVD despite optimal therapy 2
  • Has been shown to reduce cardiovascular events by approximately 80% in patients with elevated Lp(a) 2

Special Populations

• Children with elevated Lp(a) have a fourfold increased risk of acute ischemic stroke 2
• Chronic kidney disease patients have substantially increased Lp(a) levels, and Lp(a) is an independent predictor of coronary heart disease events and mortality in these patients 2
• Familial hypercholesterolemia patients with elevated Lp(a) have increased cardiovascular risk and may be predisposed to aortic valve calcification 3

Clinical Pearls and Pitfalls

• Lp(a) levels are genetically determined and remain relatively stable throughout life, making a single measurement usually sufficient 4
• Patients with elevated Lp(a) are less likely to achieve target LDL-C with standard therapies 3
• In patients with very low LDL-C (<20 mg/dL), Lp(a) levels tend to be lower (mean 22 nmol/L) compared to those with higher LDL-C (>100 mg/dL), where Lp(a) levels are higher (mean 49 nmol/L) 3
• Hormone therapies (estrogens, testosterone) can reduce Lp(a) but are not recommended specifically for this purpose 1

Future Directions

• Antisense oligonucleotides targeting Lp(a) show promising results with up to 90% reductions in Lp(a) levels 5
• Ongoing clinical trials will determine whether specific Lp(a) lowering reduces cardiovascular events 5, 6