Statins: coming to a town near you

Statins are a big deal in pharmaceuticals, if you haven’t already heard of them, you will do. They are really freaking successful and they’re only going to get bigger. In 2008, atorvastatin was the best-selling branded pharmaceutical in the world, which is one hell of an achievement, when you think about it. What do statins do then, that has made them such an amazing commercial success? They lower cholesterol, of course.
It’s reasonably easy to see why drugs that effectively lower cholesterol would be extremely successful in modern Western medicine. The British Heart Foundation reported 88,236 deaths from coronary heart disease in the UK in 2008, and high cholesterol is a well-established risk factor for heart disease. If statins can help prevent heart disease then clearly they’re Pretty Darn Good News. So how do these butter-defying little tablets work?

Cholesterol in the body is produced by a series of chemical reactions in the liver. The reaction pathway starts with 3-hydroxy-3-methylglutaryl-co-enzyme A (HMG-CoA), which has to undergo 29 (count ‘em!) chemical reactions to eventually become cholesterol. The first reaction is the conversion of HMG-CoA to mevalonic acid (or mevalonate, same thing) and this reaction is helped along by an enzyme, HMG-CoA reductase. This is where statins come in. Statins bind to HMG-CoA reductase and in doing so, stop HMG-CoA itself from being able to bind the enzyme and be converted to mevalonate. If mevalonate is not produced then the next step of the reaction pathway cannot take place either, and so the production of cholesterol is inhibited.

This sexy little molecule is HMG-CoA reductase, the enzyme targeted by statins
However, this clearly doesn’t stop the cholesterol in clotted cream, cake and buttery goodies getting into your body. But with cholesterol production inhibited, the levels of cholesterol in the liver will drop. Cells in the liver can sense this and respond by causing the release of a sterol regulatory element binding protein. This protein stimulates the production of low density lipoprotein (LDL) receptors. Low density lipoproteins are carriers of cholesterol in the bloodstream. The increased numbers of LDL receptors head off to the liver cell membrane where they hang out with big nets, fishing passing LDLs out of the bloodstream. Once the LDLs are in the liver, the cholesterol they contain is converted into bile salts and excreted. Bye-bye cholesterol!
Part of the reason that statins are so successful is that they are very effective, and additionally they are considered very safe. There are some associated side effects, most commonly raised levels of liver enzymes and some muscle breakdown problems; however these are rare, and since there is no such thing as a side-effect-free drug, statins are comparatively very safe to prescribe.
The big question with statins is who should be taking them? There are big debates about the cost versus the benefits; whether the cost of providing statins is worth the health benefits that it provides. It all comes down to price versus effectiveness. Currently, statins are recommended for people at high risk of cardiovascular disease (people who are considered to have 20% or higher risk of some sort of cardiovascular event within 10 years). However, a study by Dr Niteesh Choudhry and colleagues, published in November 2010, concluded that it may also be worth prescribing them to adults classified as being at moderate risk. Apparently…
“If the 23 million Americans at moderate risk of cardiovascular disease were treated for 4.3 years, an estimated 85,800 strokes and 383,000 major coronary events would be prevented — but the cost would be at least $40 billion.”
So really you’re trying to decide whether that many lives are worth that much money (bearing in mind the cost of treating these people if they do have their stroke or “cardiovascular event”). I’m glad that’s not my decision, to be honest. Particularly as there are, as ever, some complicating factors. Statins do reduce cholesterol, but high cholesterol isn’t the only cause of heart disease. And statins aren’t a substitute for a healthy lifestyle. In fact, it’s almost impossible to truly predict just how effective statins are in preventing heart disease; the numbers above are really a guess, a very educated guess, but still, the whole thing is an estimation game, based on statistics and money.
So what’s the answer? As with all these issues, a healthier lifestyle is the holy grail of solutions, but if the drugs can help, should we use them? And how do we decide who uses them, and whether the benefits outweigh the costs? More longer-term research will help come up with answers, but at the end of the day, it’s always going to be a matter of balancing the risks. And possibly eating less cake.


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