A replacement for statins? Too early to say, but promising.

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Screen Shot 2015-03-17 at 1.57.35 PMAs reported by Ed Mr. Pharmaceuticals Silverman, in yesterday s Wall Street Journal, there may be a new paradigm for significantly lowering LDL (bad) cholesterol, and reducing heart disease.

The statins (e.g. Lipitor) were the first class of lipid-modifying drugs that really worked. They inhibit cholesterol biosynthesis in the liver, and this in turn causes secondary effects an increase of LDL uptake by the liver, which drops blood levels of both LDL and total cholesterol. This in turn causes a reduction in cardiovascular events and deaths, although there are differing opinions about the magnitude of this reduction.

A new class of LDL-lowering drugs is being investigated by Amgen (evolocumab), and Sanofi, in partnership with Regeneron (alirocumab). They work in a completely different manner.

The new drugs are called PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors, and their mechanism of action is quite complex. Also, as the names indicate, these are not pills, rather, injectable biological drugs. (The ab ending on a drug means that it is an antibody they are injected).

This also means they will be much more expensive than statins. Almost all the statins are now generic, and their prices are commensurately low. Biological drugs are almost always more expensive than pills, and must be injected rather than swallowed.

How well do they work? Silverman says, Both drugs reduced LDL cholesterol by about 60%. As to heart attacks, strokes and other such risks, the Amgen study, which involved 4,465 people, found that after nearly a year of follow up, less than 1% of those given its evolocumab drug suffered a major heart-related event, compared with slightly more than 2% on a placebo.

ACSH s Dr. Josh Bloom comments, If these numbers hold up in phase III trials, this could be a major advance. Following a year of treatment, evolocumab cut the number of cardiovascular events by more than half. Pretty impressive.

But, there are other factors at play. First is whether the new therapy is cost effective. Although the injectable drugs will certainly be pricey, it may be possible to give a monthly injection, although that will undoubtedly still be far more expensive than generic statins. And statins have known side effects in some people, although they are uncommon. The injectables do have some as well.

Dr. Bloom says, We could be looking at an entirely different, more beneficial paradigm for treatment of heart disease the nation s number one killer. There are many questions that remain, but given the number of patients trying the drug, as well as it s effect, this could be a major medical advance.

(The full NEJM paper can be found here.)