What is the treatment for elevated Lipoprotein(a) (LPA)?

Treatment of Elevated Lipoprotein(a)

The primary treatment for elevated Lp(a) is aggressive LDL-cholesterol reduction to lower targets than standard goals, as Lp(a) contributes to residual cardiovascular risk at any achieved LDL-C level. 1

Risk Stratification and Treatment Thresholds

Elevated Lp(a) is defined as >30 mg/dL (>75 nmol/L), representing the 75th percentile in white populations where cardiovascular risk begins to increase. 2, 1 The European guidelines use >50 mg/dL (~100-125 nmol/L) to define significant risk, though treatment consideration should not be delayed at lower levels with additional risk factors. 1, 3

Risk increases progressively with higher Lp(a) levels, with particularly high risk at >100 mg/dL. 1

Primary Management Strategy: Aggressive LDL-C Reduction

The cornerstone of management is intensive LDL-cholesterol lowering, as patients with elevated Lp(a) have higher cardiovascular event rates at any achieved LDL-C level. 2, 1 This is critical because standard LDL-C laboratory measurements include the cholesterol content of Lp(a), potentially overestimating true LDL-C and affecting achievement of targets. 1, 3

Important caveat: Statins and ezetimibe may actually increase Lp(a) mass and Lp(a)-C levels in some patients, though they remain essential for LDL-C reduction. 1, 3

Pharmacological Options for Lp(a) Reduction

First-Line Lp(a)-Specific Therapy

Niacin (nicotinic acid) is currently the most recommended pharmacological treatment specifically for Lp(a) reduction, achieving 30-35% reductions at doses up to 2000 mg/day. 1, 3 The American College of Cardiology recommends considering niacin (immediate- or extended-release formulation) up to 2000 mg/day, optimally in conjunction with glycemic control and LDL control. 1

Titrate extended-release niacin from 0.5 g up to 2 g over several weeks to minimize flushing side effects. 4 Crystalline niacin allows titration to 2 g three times daily for higher doses, though flushing is more prominent. 4

PCSK9 Inhibitors for High-Risk Patients

PCSK9 inhibitors (evolocumab or alirocumab) reduce Lp(a) by approximately 25-30% while providing an additional 50-60% LDL-C reduction. 1, 5 These should be considered for high-risk patients with Lp(a) >100 mg/dL or additional risk factors. 1

Evidence from randomized trials (FOURIER, JUPITER, LIPID) demonstrates that PCSK9 inhibitors reduce cardiovascular events, with some sophisticated analyses suggesting benefit beyond LDL-C lowering alone. 2, 5

Additional Pharmacological Options

• Fibrates: Reduce Lp(a) by up to 20%, with gemfibrozil showing the highest effect. 3
• Aspirin: Low-dose aspirin provides modest (10-20%) reductions in Lp(a) levels and should be considered in primary prevention for patients with elevated Lp(a). 3, 6
• L-Carnitine: Can reduce Lp(a) by 10-20%. 3

Lipoprotein Apheresis for Refractory Cases

Lipoprotein apheresis is the most effective current treatment, reducing Lp(a) by up to 80%, and should be considered for patients with Lp(a) >60 mg/dL who develop cardiovascular events or disease progression despite optimal medical therapy. 2, 1, 3

German studies demonstrated reduction of cardiovascular events by approximately 80% (MACE rate per year: pre-apheresis 0.41-2.80, post-apheresis 0.08-0.14) with lipoprotein apheresis in CVD patients with Lp(a) >60 mg/dL and LDL-C ~100 mg/dL on maximally-tolerated therapy. 2

Apheresis also improves coronary blood flow by MRI and reduces frequency of angina in patients with refractory angina and elevated Lp(a) >60 mg/dL. 2

Special Populations Requiring Attention

Familial Hypercholesterolemia

Patients with FH and elevated Lp(a) have increased cardiovascular risk and may be predisposed to aortic valve calcification. 2, 1 Consider more intensive LDL-C reduction with PCSK9 inhibitors or lipoprotein apheresis in FH individuals with higher Lp(a) levels. 2

Pediatric and Young Adult Stroke

Children with elevated Lp(a) have a fourfold increased risk of acute ischemic stroke. 1 The risk of recurrent ischemic strokes increases by more than 10-fold in patients with Lp(a) >90th percentile. 1

Chronic Kidney Disease

Lp(a) levels are substantially increased in persons with end-stage renal disease and chronic kidney disease, and Lp(a) is an independent predictor of incident coronary heart disease events and mortality in CKD patients. 1

Secondary Prevention Considerations

Prolonged dual antiplatelet therapy should be considered in secondary prevention for patients with elevated Lp(a). 6 This addresses the prothrombotic properties of Lp(a) beyond its atherogenic effects.

Common Pitfalls to Avoid

• Do not rely solely on LDL-C levels for cardiovascular risk assessment without considering Lp(a), as this underestimates total risk. 7
• Do not assume statins will lower Lp(a) – they may increase levels in some patients despite effectively lowering LDL-C. 1, 3
• Do not use hormone replacement therapy (estrogens, testosterone) specifically for Lp(a) reduction, despite their ability to lower levels. 3, 4
• Remember that standard LDL-C assays include Lp(a)-cholesterol content, potentially affecting interpretation of LDL-C targets. 1, 3