Cholesterol and Vascular Disease Part 6: LDL-Apheresis and Other Novel Cholesterol Strategies

September is National Cholesterol Education Month. In support of this important educational initiative we are republishing our six part series on cholesterol and the role it plays in cardiovascular disease.

Note: Seventy-one million American adults have high cholesterol, but it is estimated that only one-third of them have the condition under control.

Today’s final post in my six-part series on cholesterol examines one FDA approved non-medication treatment for severely elevated LDL cholesterol, and three novel medications on the horizon.

LDL-Apheresis is a non-drug therapy for patients with vascular disease and LDL-C > 200. It is reserved for patients with a genetic disorder called Familial Hypercholesterolemia (FH), or those individuals who cannot tolerate standard medications but still have very high LDL levels. Therefore, this treatment is clearly not for everyone. In a manner similar to dialysis, patients are connected to a filtering machine through two IV lines. Blood is withdrawn from one arm, circulated through a series of filters and returned to the body through the other arm. Typically the procedure is performed every other week. Each treatment results in a 60% to 80% reduction in LDL particles. After treatments, the LDL will rise steadily until it can be lowered once again with another therapy. Although LDLs do increase after a treatment, studies have demonstrated a nearly 75% reduction in cardiovascular events when patients are treated with LDL-Apheresis. Thus, LDL-Apheresis is a viable option for high risk patients. I am very fortunate to be able to run one of the forty or so centers in the USA, and I am happy to say that not only is the procedure extraordinarily well tolerated, but also the lipid effects are nothing short of remarkable.

As for the medications on the horizon, three deserve immediate recognition: Mipomersen, Lomitapide, and REGN727. These are all currently “experimental” but deserve mention not just because they will likely soon be on the market, but because each one represents a truly fresh way to lower LDL.

  • Mipomersen, licensed by Genzyme, is a second generation antisense oligonucleotide that is administered weekly by injection. It dramatically lowers LDL. The English translation is that this drug thwarts our body’s LDL production mechanism at the DNA level. DNA’s job is to produce mRNA in order to translate DNA’s protein-producing knowledge into the actual creation of proteins. Mipomerson binds and inactivates the mRNA that carries the code for the essential protein in every LDL particle, apoB. Without apoB, LDL cannot be created. Mipomerson does not block cholesterol production; it stops our body from producing too many LDL particles. Very different from the way statins work!
  • Lomitapide – owned by Aegerion – works differently. The first step in normal LDL particle construction is the merger of apoB (a protein) with triglycerides (fats). Even within cells, fats do not float freely; they must be chaperoned from one place to another. (Remember, water – blood – and fat do not mix!) The chaperone for triglycerides in the intestinal and liver cells is called MTP, or Microsomal Triglyceride Transfer Protein. Lomitapide inhibits MTP; it is our first MTP inhibitor. By blocking the transfer of enough triglycerides to the essential apoB protein, defective LDL precursors are produced. Our bodies don’t like out-of the-ordinary substances, and so these precursors are rapidly destroyed. The result, dramatically decreased LDL (and triglyceride) levels.
  • Finally, there’s REGN727, a drug that is too young to bear a proper name. This agent utilizes yet another innovative approach to diminish LDL. If you recall from Part 4 of this series, LDL receptors bring LDL into cells. When we have a lot of LDL receptors on our liver cells, LDL levels fall, and our blood vessels are far better off. Our bodies produce a substance called PCSK9 whose role is to bind and inactivate LDL receptors. When PCSK9 levels are out of control, we destroy too many receptors and develop dangerously high levels of LDL. REGN727 is an antibody against PCSK9, so it stops our bodies from inappropriately destroying valuable LDL receptors. By doing so, it too lowers LDL. Of the three novel agents, this one is furthest from the market. It needs more thorough testing before it can be released. At this point though, confidence is high. Hopefully within a few years we will see all three of these agents helping millions of patients avoid experiencing heart attacks and strokes.

I hope you’ve enjoyed reading this series on Cholesterol and Vascular Disease as much as I’ve enjoyed writing it. Thanks for tuning in.

Visit for preventive health solutions.

Tags: , , , , , ,

No comments yet.

Post Comment