What helps to lower non-High-Density Lipoprotein (HDL) cholesterol in someone with elevated Lipoprotein(a) (Lp(a))?

From the Guidelines

To lower non-HDL cholesterol in someone with high lipoprotein(a) [Lp(a)], statins are the first-line medication, with options like atorvastatin (20-80mg daily) or rosuvastatin (10-40mg daily). If statins alone are insufficient, adding ezetimibe (10mg daily) can further reduce non-HDL levels by blocking cholesterol absorption in the intestine 1. For those needing additional reduction, PCSK9 inhibitors like evolocumab (140mg every 2 weeks) or alirocumab (75-150mg every 2 weeks) can be highly effective 1. Lifestyle modifications are essential companions to medication:

• reduce saturated fat intake
• increase soluble fiber (10-25g daily)
• exercise regularly (150 minutes weekly of moderate activity)
• maintain healthy weight
• avoid smoking
• limit alcohol. While these approaches effectively lower non-HDL cholesterol, it's essential to note that they have minimal impact on Lp(a) levels themselves, which are largely genetically determined 1. Specific Lp(a)-lowering therapies are currently in development. Regular lipid monitoring every 3-6 months is recommended to assess treatment effectiveness and adjust as needed 1.

From the FDA Drug Label

Ezetimibe Tablet reduces total cholesterol (total-C), LDL-C, apolipoprotein (Apo) B, and non-high-density lipoprotein cholesterol (non-HDL-C) in patients with hyperlipidemia. In a 2-week clinical trial in 18 hypercholesterolemic patients, ezetimibe tablet inhibited intestinal cholesterol absorption by 54%, compared with placebo

Ezetimibe may help lower non-HDL cholesterol in someone with high Lp(a) by reducing the absorption of cholesterol in the small intestine.

• The mechanism of action of ezetimibe is the inhibition of the intestinal absorption of cholesterol and related phytosterols.
• Key benefits of ezetimibe include the reduction of total cholesterol, LDL-C, apolipoprotein B, and non-HDL-C in patients with hyperlipidemia. 2

From the Research

Lowering Non-HDL Cholesterol with High Lp(a)

To lower non-HDL cholesterol in individuals with high Lp(a), several options can be considered:

• Lipoprotein apheresis (LA) has been shown to efficiently lower Lp(a) and reduce the risk of incident CV events 3.
• PCSK9 inhibitors can significantly reduce Lp(a) levels by up to 30% 3.
• Antisense oligonucleotides (ASO) have been found to have good safety and strong efficacy in lowering Lp(a) levels, with reductions of up to 90% 3.
• Statins, on the other hand, have been found to have neutral or detrimental effects on Lp(a) levels 3, 4, 5.
• Some studies have suggested that statins may even increase Lp(a) levels, although the clinical significance of this is unclear 5.

Effects of Statins on Lp(a) Levels

The effect of statins on Lp(a) levels has been studied extensively:

• A systematic review and meta-analysis found that statin therapy did not lead to clinically important differences in Lp(a) levels compared to placebo 4.
• Another study found that HMG CoA reductase inhibitors, a class of statins, actually increased Lp(a) levels by 33% despite lowering LDL cholesterol levels 5.
• However, it's worth noting that different types and intensities of statin therapy may have varying effects on Lp(a) levels, although the evidence is not conclusive 4.

Alternative Treatment Options

For individuals with high Lp(a) and non-HDL cholesterol, alternative treatment options may be considered:

• Lipoprotein apheresis (LA) and PCSK9 inhibitors may be effective in lowering Lp(a) levels and reducing CV risk 3.
• Antisense oligonucleotides (ASO) may also be a promising treatment option for lowering Lp(a) levels 3.
• Further research is needed to determine the most effective treatment strategies for individuals with high Lp(a) and non-HDL cholesterol.