How do you manage elevated Apolipoprotein B (Apo B) versus Lipoprotein(a) (Lp(a)) levels?

From the Guidelines

Managing elevated Apolipoprotein B (Apo B) and Lipoprotein(a) (Lp(a)) levels requires different approaches as they represent distinct cardiovascular risk factors. For elevated Apo B, the primary treatment involves statins such as atorvastatin (20-80mg daily) or rosuvastatin (10-40mg daily), which can reduce Apo B levels by 30-50% 1. If statins alone are insufficient, adding ezetimibe (10mg daily) can further lower Apo B by an additional 10-15%. For patients with persistently high levels despite these medications, PCSK9 inhibitors like evolocumab (140mg every 2 weeks) or alirocumab (75-150mg every 2 weeks) may be prescribed, reducing Apo B by up to 60% 1. For elevated Lp(a), treatment options are more limited. Niacin (1-3g daily) may modestly reduce Lp(a) by 15-30%, but has significant side effects including flushing and liver concerns. PCSK9 inhibitors can lower Lp(a) by 20-30% 1. The novel antisense oligonucleotide pelacarsen is showing promise in clinical trials specifically for Lp(a) reduction, with the ability to lower plasma Lp(a) levels by up to 90% or more 1. For both conditions, lifestyle modifications are essential:

• reducing saturated fat intake
• increasing physical activity
• maintaining healthy weight
• avoiding smoking. The different approaches reflect the underlying biology - Apo B represents the total number of atherogenic particles, while Lp(a) is a genetically determined, LDL-like particle with additional thrombotic properties that doesn't respond well to conventional lipid-lowering therapies 1. It is also important to consider risk-enhancing factors, such as family history of premature ASCVD, LDL-C levels of 4.1 mmol/L (160 mg/dL) or higher, and elevations in apolipoprotein B or lipoprotein(a) levels, when making treatment decisions 1.

From the FDA Drug Label

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 Primary Hyperlipidemia in Adults Atorvastatin calcium given as a single dose over 6 weeks, significantly reduced total-C, LDL-C, apo B, and TG.

Management of Elevated Apolipoprotein B (Apo B) versus Lipoprotein(a) (Lp(a)) levels:

• The FDA drug label for atorvastatin provides information on the reduction of Apo B levels, but does not directly compare the management of elevated Apo B versus Lp(a) levels.
• Apo B levels are reduced by atorvastatin, as shown in the dose-response trials (Table 8) and active-controlled trials (Table 9).
• There is no direct information on the management of Lp(a) levels in the provided drug label. 2

From the Research

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

• The management of elevated Apo B and Lp(a) levels involves a combination of lipid-modifying therapies, with the primary focus on reducing low-density lipoprotein cholesterol (LDL-C) to the lowest attainable value with a high-potency statin 3.
• For patients with elevated Lp(a) levels (≥30 mg/dL) and residual LDL-C elevations (≥70-100 mg/dL) despite maximum-potency statins or combination statin therapy, the clinician may consider adding niacin (up to 2 g/d) 3.
• Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been shown to decrease Lp(a) and cardiovascular events, particularly in high-risk patients with elevated Lp(a) 4, 5.
• The use of PCSK9 inhibitors can significantly reduce LDL-C and Lp(a) levels in patients with acute coronary syndrome (ACS) and complex higher-risk and indicated patients (CHIPs) 5.
• The addition of PCSK9 inhibitors to background niacin therapy can further lower Lp(a) levels, with a median percent reduction of -15.3% 6.

Apolipoprotein B (Apo B) as a Marker of Cardiovascular Risk

• Apo B is considered a more accurate measure of cardiovascular risk and a better guide to the adequacy of lipid lowering than LDL-C or non-high-density lipoprotein cholesterol (HDL-C) 7.
• The 2019 European Society of Cardiology/European Atherosclerosis Society Guidelines concluded that Apo B can be measured more accurately than LDL-C or non-HDL-C, and that it should be the primary metric to guide statin/ezetimibe/PCSK9 therapy 7.

Lipoprotein(a) (Lp(a)) as a Risk Factor for Atherosclerotic Cardiovascular Disease

• Lp(a) is an independent risk factor for the development of atherosclerosis, and is closely correlated to stent thrombosis and restenosis 5.
• Elevated Lp(a) levels are associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD), particularly in patients with a personal or family history of premature cardiovascular disease, familial hypercholesterolemia, or recurrent cardiovascular events 3, 4.