Monday, May 21, 2012

Back to Statins in the Water Supply--But On What Basis?

In the beginning was the polypill. This hypothetical product was first proposed by Wald and Law in 2003, based on the idea that with a general population at fairly high risk for heart disease, it made sense simply to put everyone above a certain age on a combination pill containing a statin for cholesterol, aspirin, and one or more drugs for blood pressure. A recent review by Katherine M. Carey, PharmD and colleagues reviewed a number of studies that tried to assess the vaolue and safety of one or another form of polypill and concluded that at best the results would be modest (subscription may be required):

Well, now says The Lancet, forget the polypill. Just put everyone above age 50 on a statin:

This advice is based on a recently-published-on-line meta-analysis by the Cholesterol Clinical Trialists (subscription required). Their study reviewed a total of 27 clinical trials of statins as primary prevention (that is, for people without known heart or blood vessel disease). They concluded that on combining all these trials, there was a clear advantage to using statins for primary prevention, and that the more they lowered your LDL ("bad") cholesterol, the better they were as a preventive.

To regular readers of this blog, such a study would require some explanation, because it contradicts evidence about statins and primary prevention that has by now been fairly well established, even if little understood by many physicians as well as the general public. See for example:
--which discusses the low level of evidence that statins are any good for primary prevention, as well as raising questions about whether they do whatever good they do by means of lowering cholesterol.

I have been privy to some e-mail discussions among statin and evidence-based-medicine experts, and I believe that several are planning to write letters and commentaries disputing the conclusions of the new Lancet meta-analysis. I am not at liberty yet to share the details of their reasoning. However, I can point to one press response to the Lancet statement about putting everyone on a statin:

Melinda Wenner Moyer, writing for Scientific American, interviewed several critics and pointed out a few of the problems with the CTT meta-analysis. The biggest flaw pojinted out by the critics she quotes is that while the CTT study pupports to demonstrate that statins are good for primary prevention, fully 60 percent of the study participants in the 27 pooled clinical trials had existing heart or vessel disease. To extrapolate from that population to the "low risk" patient identified in the title of the CTT study hardly seems kosher. The othet major criticism is that almost surely, the CTT trial vastly underestimates the frequency of averse reactions to statin drugs--in part, perhaps, because at least some of the clinical trials were designed specifically to exclude patients who had those adverse reactions, again a not-very-kosher study design.

I believe that as the weeks pass there will be even more serious criticisms lodged against the CTT study, so stay tuned.

Wald NJ, Law MR. A strategy to reduce cardiovascular disease by more than 80%. BMJ 326:1419-24, 2003.

Cholesterol Clinical Trialists' (CTT) Collaborators. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. Lancet doi:10.1016/S0140-6736(12)60367-5, published on line May 17, 2012.

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