What is the management for patients with elevated Apolipoprotein B (Apo B) and Lipoprotein(a) (Lp(a)) levels?

From the Guidelines

Management of elevated Apolipoprotein B (Apo B) and Lipoprotein(a) [Lp(a)] should focus on aggressive lipid-lowering therapy and cardiovascular risk reduction, with statins as the first-line treatment, according to the most recent guidelines 1. For elevated Apo B, high-intensity statins like atorvastatin 40-80mg or rosuvastatin 20-40mg daily are most effective. If statins alone are insufficient, ezetimibe 10mg daily can be added. For patients with persistently elevated Apo B despite these medications, PCSK9 inhibitors (evolocumab 140mg every 2 weeks or alirocumab 75-150mg every 2 weeks) may be prescribed, as supported by recent studies 1. For elevated Lp(a), which is largely genetically determined, treatment options are more limited. While statins don't significantly lower Lp(a), niacin (1-3g daily) may provide modest reductions, as noted in earlier research 1. PCSK9 inhibitors can reduce Lp(a) by 20-30%. For very high Lp(a) levels, specialized treatments like lipoprotein apheresis may be considered in high-risk patients, as discussed in recent guidance 1. Some key points to consider in managing elevated Apo B and Lp(a) include:

• Lifestyle modifications are essential: Mediterranean diet, regular exercise (150 minutes weekly), weight management, smoking cessation, and blood pressure control.
• Treatment should be individualized based on overall cardiovascular risk assessment, with more aggressive therapy for patients with established cardiovascular disease or multiple risk factors.
• The use of lipoprotein apheresis may be considered in patients with very high Lp(a) levels or those who are refractory to other therapies.
• Recent studies have highlighted the importance of aggressive lipid-lowering therapy in reducing cardiovascular risk in patients with elevated Apo B and Lp(a) 1.

From the FDA Drug Label

Primary Hyperlipidemia in Adults Rosuvastatin reduces Total-C, LDL-C, ApoB, non-HDL-C, and TG, and increases HDL-C, in adult patients with hyperlipidemia and mixed dyslipidemia Atorvastatin calcium reduces total-C, LDL-C, apo B, and TG, and increases HDL-C in patients with hyperlipidemia (heterozygous familial and nonfamilial) and mixed dyslipidemia

The management for patients with elevated Apolipoprotein B (Apo B) and Lipoprotein(a) (Lp(a)) levels involves reducing Total-C, LDL-C, ApoB, non-HDL-C, and TG, and increasing HDL-C.

• Rosuvastatin and Atorvastatin are two statins that have been shown to be effective in reducing ApoB levels.
• The goal of treatment is to slow the progression of atherosclerosis and reduce the risk of major cardiovascular events.
• The choice of treatment should be individualized based on the patient's risk factors, medical history, and response to therapy 2 3.

From the Research

Management of Elevated Apolipoprotein B (Apo B) and Lipoprotein(a) (Lp(a)) Levels

• The management of patients with elevated Apolipoprotein B (Apo B) and Lipoprotein(a) (Lp(a)) levels is crucial in reducing the risk of cardiovascular disease (CVD) 4, 5.
• Elevated Lp(a) levels are a risk factor for CVD, aortic valve stenosis, and heart failure, and can increase the risk of developing CVD even when LDL cholesterol (LDL-C) levels are within the recommended range 4.
• Lifestyle changes and standard lipid-lowering treatments, such as statins, niacin, and cholesteryl ester transfer protein inhibitors, are not highly effective in reducing Lp(a) levels 4, 5.
• PCSK9 inhibitors can reduce Lp(a) levels by 25-30%, while mipomersen can decrease Lp(a) levels by 25-40%, but its use is burdened with important side effects 4.
• Apheresis is currently the most effective and tolerated treatment for patients with high Lp(a) plasma levels, while antisense oligonucleotides, small interfering RNAs, and microRNAs are promising perspectives 4, 6.

Treatment Options for Elevated Lp(a) Levels

• Emerging nucleic acid-based therapies, such as the antisense oligonucleotide pelacarsen and the small interfering RNA olpasiran, have potent Lp(a)-lowering effects and appear safe 5.
• The hepatocyte-directed antisense oligonucleotide AKCEA-APO(a)-LRx has been shown to reduce Lp(a) levels in a dose-dependent manner in patients with established CVD and elevated Lp(a) levels 6.
• Statins, such as rosuvastatin, can reduce circulating concentrations of atherogenic ApoB-containing lipoproteins by decreasing the production of VLDL in the liver and increasing the clearance of these particles through upregulation of LDL receptors in the liver 7.

Genetic Epidemiological Perspective

• Genetic association studies have revealed that Lp(a) is robustly, independently, and causally associated with a broad range of cardiovascular and valvular heart diseases 8.
• Up to 1 billion people around the globe may have an Lp(a) level that places them in a high-risk category, and Lp(a) has emerged as one of the most important genetic determinants of human lifespan and healthspan 8.