The future treatment of high cholesterol

In my last blog (see here), I noted that CDC estimates only 1 in 3 people with high cholesterol are adequately treated.

There is a new class of injectable drugs to treat high cholesterol: PCSK9 inhibitors. Two such drugs were approved by the FDA in the past few weeks: Praluent (the generic name is alirocumab) and Repatha (aka evolocumab). PCSK9 is a natural enzyme found in the body that raises LDL (bad cholesterol). PCSK9 works in the liver, which has receptors that grab LDL and destroy it. PCSK9 lowers these receptors. Blocking PCSK9 increases the number of receptors, so more LDL is removed from the blood. The effects are pretty impressive… These new drugs have been shown to cut LDL levels by approximately 50-70+% (see herehere, and here).

Statins (drugs such as Lipitor [aka atorvastatin], Zocor [simvastatin], Crestor [rosuvastatin], etc) not only lower LDL, they also prevent heart attacks and strokes. It’s believed the clinical benefit is a direct result of lowering LDL, but scientists don’t know for certain whether the path to lowering LDL matters. For example, does lowering LDL by using PCSK9 inhibitors also lower heart attacks and strokes? There are two large trials being done to answer this question (the set-up of one of these trials is described here). Results are due out in 2016 or 2017.

Until we have a definitive answer, nature provides a clue. Specifically, people who have genetic mutations resulting in low levels of PCSK9 have a markedly low rate of heart disease (the genetic mutation is a natural form of these drugs, as the result is blocking PCSK9).

I’m hopeful and optimistic that PCSK9 inhibitors will be another meaningful tool to keep people living healthier and longer.

Wonderful stuff.


Source: PCSK9 (Wikipedia); Effect of alirocumab, a monoclonal antibody to PCSK9, on long-term cardiovascular outcomes following acute coonary syndromes: Rationale and design of the ODYSSEY Outcomes trial (Science Direct); Praluent FDA label (; Repatha FDA label (; FDA Briefing Document Endocrinologic and Metabolic Drugs Advisory Committee (; Heart Disease Fact Sheet (The Center for Disease Control); Effect of Evolocumab or Ezetimibe Added to moderate or High-Intensity Statin Therapy on LDL-C Lowering in Patients With Hypercholesterolemia The LAPLACE-2 Randomized Clinical Trial (The Journal of American Medical Association); Efficacy and Safety of Alirocumab in Reducing Lipids and Cardiovascular Events (New England Journal of Medicine); Molecular Characterization of Loss-of-Function Mutations in PCSK9 and Identification of a Compound Heterozygote (National Library of Medicine)


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