What is the management for elevated apolipoprotein (Apo) levels?

From the Guidelines

Management of high apolipoprotein levels, particularly apolipoprotein B (apoB), should start with lifestyle modifications and first-line pharmacotherapy with statins, such as atorvastatin (20-80 mg daily) or rosuvastatin (10-40 mg daily), to effectively lower apoB levels and reduce the risk of atherosclerotic cardiovascular disease (ASCVD) events by 22%, all-cause mortality by 10%, and mortality due to coronary heart disease by 20% per 1.0 mmol/L of achieved reduction in LDL-C levels 1.

Lifestyle Modifications

• Dietary changes including reduced saturated fat and cholesterol intake
• Increased consumption of fruits, vegetables, whole grains, and lean proteins
• Regular physical activity (at least 150 minutes of moderate-intensity exercise weekly)

Pharmacotherapy

• First-line: statins such as atorvastatin (20-80 mg daily) or rosuvastatin (10-40 mg daily)
• Second-line: ezetimibe (10 mg daily) for patients not achieving targets with statins alone
• Third-line: PCSK9 inhibitors like evolocumab (140 mg every 2 weeks) or alirocumab (75-150 mg every 2 weeks) for those with persistently elevated levels despite maximum tolerated statin therapy

Monitoring and Treatment Goals

• Regular monitoring of lipid profiles every 3-6 months to assess treatment efficacy
• Targeting apoB levels to reduce the risk of ASCVD events, with a treatment goal of lowering LDL-C levels to <1.4 mmol/L (55 mg/dL) and achieving a reduction by at least 50% from baseline 1
• Consideration of lipoprotein apheresis for patients with homozygous familial hypercholesterolemia (HoFH) who do not achieve guideline-recommended LDL-cholesterol goals despite maximally tolerated combination drug therapy 1

From the FDA Drug Label

Table 14: Lipid-modifying Effects of Rosuvastatin in Pediatric Patients 7 to 15 years of Age with HoFH After 6 Weeks ... ApoB (mg/dL)268235-17.1% (-29.2, -2. 9) 3

Table 13: Lipid-Modifying Effects of Rosuvastatin in Pediatric Patients 10 to 17 years of Age with HeFH (Least-Squares Mean Percent Change from Baseline To Week 12) ... ApoB 1Median percent change 2-30%-13% 2-32%

Table 15: Lipid-modifying Effects of Rosuvastatin 10 mg and 20 mg in Adult Patients with Primary Dysbetalipoproteinemia (Type III hyperlipoproteinemia) After Six Weeks by Median Percent Change (95% CI) from Baseline (N=32) ... Apo-E16.0-42.9 (-46.3, -33.3) -42.5 (-47. 1, -35. 6)

Management for high apolipoprotein

• Rosuvastatin reduces ApoB levels in patients with hyperlipidemia, with median percent changes ranging from -17.1% to -42.9% depending on the patient population and dosage.
• The reduction in ApoB levels is consistent across different patient populations, including pediatric patients with HoFH and adult patients with primary dysbetalipoproteinemia.
• The exact management strategy for high apolipoprotein levels may depend on the individual patient's condition and medical history, but rosuvastatin has been shown to be effective in reducing ApoB levels in various clinical trials 2.
• Atorvastatin also reduces ApoB levels, with median percent changes ranging from -26.5% to -34% depending on the patient population and dosage 3.

From the Research

Management for High Apolipoprotein

• The management of high apolipoprotein levels is crucial in reducing the risk of atherosclerotic cardiovascular disease (ASCVD) 4.
• High levels of lipoprotein(a) [Lp(a)] are causal for ASCVD, and Lp(a) is the most prevalent inherited dyslipidemia and strongest genetic ASCVD risk factor 4.
• Targeted apolipoprotein(a) [apo(a)]-lowering therapies that reduce Lp(a) levels in patients with high Lp(a) are in phase 3 clinical development 4.

Role of Statins in Management

• Statin therapy alters the relationship between apolipoprotein B and low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol targets in high-risk patients 5.
• Reducing LDL-C to a pre-determined goal may still leave an excess of atherogenic lipoproteins, as reflected in apoB levels 5.
• Atorvastatin and rosuvastatin at maximal doses are both highly effective in lowering low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels, and also reduce apolipoprotein B-48 and remnant lipoprotein cholesterol levels 6.

Importance of Apolipoprotein B

• Apolipoprotein B (apoB) is a more accurate measure of cardiovascular risk and a better guide to the adequacy of lipid lowering than low-density lipoprotein cholesterol (LDL-C) or non-high-density lipoprotein cholesterol (HDL-C) 7.
• Using LDL-C to guide the adequacy of lipid lowering therapy represents an interpretive error of the results of the statin/ezetimibe/PCSK9 inhibitor randomized clinical trials, and therefore apoB should be the primary metric to guide statin/ezetimibe/PCSK9 therapy 7.

New Lipid-Lowering Therapies

• PCSK9 inhibitors (PCSK9i), such as evolocumab and alirocumab, are monoclonal antibodies that inactivate the liver proprotein convertase subtilisin kexin 9 (PCSK9), leading to a profound reduction in circulating LDL particles 8.
• PCSK9i as adjunct to statin therapy can reduce LDL-C by 50-60% above that achieved by statin therapy alone, and may reduce cardiovascular events and all-cause mortality in patients with clinical ASCVD 8.