Map of life expectancy at birth from Global Education Project.

Monday, December 02, 2013

About that statin controversy

I'm not a cardiologist or an epidemiologist and I don't like to make authoritative noises when I'm really just faking it. However, the recent brouhaha over new guidelines for the use of statins  promulgated by the American College of Cardiology and American Heart Association touches on many issues I do think about with some pretense of expertise, so I feel compelled to comment insofar as I can.

For those who haven't been keeping up, formerly doctors were urged to prescribe these medications with a goal of lowering Low Density Lipoprotein (LDL), the so-called "bad cholesterol." The goal of  prescribing was to get  LDL as low as possible, all the way down to 70. The new guidelines no longer call for trying to meet any particular cholesterol target; rather, the indication for prescribing is a score on a risk algorithm to predict the probability of heart attack or stroke within 10 years.

The controversy centered around three main issues. First, the risk score calculator was said by many to be inaccurate, and to overestimate risk. The whole idea of a risk cutoff in the first place is to try to balance the potential benefits of taking statins against the potential risks and costs. Obviously they cost a bit of money, although they're quite inexpensive on a per-dose basis now that many different generics are available. There are some possible side effects, including an increased risk for diabetes which would largely defeat the purpose. And a lot of people nowadays already take a lot of pills -- nowadays it's commonplace for people to have 5 or 10 prescriptions. When people have that many pills to take, a lot can go wrong, including a low likelihood that they'll take all of them as prescribed. That means statins could crowd out other medications that might be more important for some people. There's also a psychological burden. And we don't really know much of anything about possible interactions between statins and other drugs.

Another problem is that abandonment of the cholesterol target seems perverse. If statins work by reducing LDL, then isn't that the reason for prescribing them and shouldn't LDL levels be our measure of whether they are working? This is a dirty little secret of statins - it isn't clear that's the mechanism by which they reduce risk of cardiovascular disease at all. Adding other medications that further reduce LDL has not been found to provide added benefit. Many people suspect that it's actually an anti-inflammatory effect, or some other unknown mechanism, that's doing the job. But if we don't even know how they work or exactly what they are doing to our bodies, shouldn't we be more cautious?

Finally there are the usual complaints about potential conflicts of interest among the panel members, some of whom have received drug industry money.

I don't have the time or probably the expertise to evaluate all the arguments about how to balance these considerations in the face of uncertainty, but John Ioannidis comes to the rescue. If I can summarize what he seems to be saying, the fact is that nobody has an ironclad case either way. The panel worked through immense amounts of data and in the end, they had to make a best judgment, which might be wrong in either direction. It's obviously worth a lot to reduce the population risk of stroke and heart attack by even a couple of percentage points per year. Many people, including me, have a predisposition to perceive overtreatment but undertreatment is bad too.

What Ioannidis says is that what we need is what we don't have -- large scale randomized controlled trials in representative populations that can definitively answer the risk/benefit question. That would take multi-megabucks over ten or more years. Sadly, people get dug in on their own answers to unanswered questions and waste time yelling at each other when they ought to be looking for definitive evidence. That seems to be the situation here.

This is no doubt a highly unsatisfying blog post but that's the way it is.

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