Richard Lehman: Where next with statins?

richard_lehmanThe Lancet‘s lengthy review on statins is masterly in its discussion of many fundamental issues about trial methodology and interpretation, and makes an excellent case for the overall benefits of statins for cardiovascular protection. But this is not new news. The discussion of adverse effects is theoretically sound but offers no new data and does not match clinical experience. And the implications of all this for discussion with individuals were far from clear to me. So I put down a few points that stood out for me in this long-running debate.  

  1. The protective effects of statins are not in doubt and are proportional to the degree of cardiovascular risk. I agree with Jeremy Sussman (University of Michigan).Statins remain among the most important advances in medical history and have prevented untold heart attacks and strokes. They reduce rates of heart attacks and strokes in essentially all people though they prevent non-fatal events at greater rates than fatal ones.” This is taken from Larry Husten’s excellent blog.
  2. The harms of statins are generally mild and reversible. But muscle pain and fatigability are not a figment of misattribution and public misinformation. They are too prevalent and recurrent in people who desperately want to stay on statins. Rather than discount a widely observed phenomenon, we should ask why there is such a mismatch with reporting in the trials. There is an urgent need for studies in the elderly, to test the hypothesis that their borderline daily functioning may be impaired by statins, tipping people into deconditioning and dependency.
  3. Although the protective effect of statins is proportionate to their pharmacological action on LDL-C, if does not follow that all LDL-lowering drugs can be assumed to be protective, or that this is necessarily their sole mode of protective effect. The Clinical Trials Support Unit has received the hundreds of millions of pounds to devise and conduct trials on other classes of LDL-lowering drugs. So far only statins have proved convincingly effective in reducing real events. The most promising new drug for cardiovascular protection, empagliflozin, does not work by LDL-C reduction.
  4. The issue of induced type 2 diabetes is just an artefact of the way we define the threshold for T2DM. Statins often cause a small rise in blood sugar, which would only be of significance if it was associated with an increase in macrovascular or microvascular disease. On the contrary, statins reduce macrovascular disease end-points, and there is no evidence to suggest that they increase eye or kidney microvascular disease (which are very rare in the glucose range we are talking about).
  5. The main adverse effect of statins is to induce arrogance in their proponents. The evidence for this class of drugs is massive and the areas of controversy are quite small. Most of the current debate consists of throwing blame at The BMJ for creating public doubt about statins in two short articles. So it has become an argument about communicating evidence to the public and to individuals, and this is something the Lancet authors seem to think should be done by authoritative persuasion based on numbers-needed-to-treat. In fact the NNTs for statins are generally much too large to be persuasive for individuals, and they are in any case not evenly distributed across individuals. Nobody has devised the ideal decision tool, partly because we are only just beginning to take account of how human beings actually react to different kinds of risk framing. A very important article on this appeared earlier this year, and you can read Andy Hutchinson’s and my comments on it in a blog that is deeply hidden on the NICE website.

Nobody can even make an informed guess about how many people would or would not take statins—especially for primary prevention—if they were fully informed about potential benefits and harms, and allowed to make the decision themselves. When the NICE guidance appeared last year, it was clear that this would take at least half an hour, potentially for every symptomless adult in the population. The alternative is for lesser breeds of doctor to heed the command of experts and simply tell all these people what to do based on computer prompts about cardiovascular risk, in 10-minute appointments usually made for other reasons. Should people then experience side-effects, they should be firmly told that the trials show they cannot be due to statins. If this was ever the real world, it is certainly not the one we are living in now. Taking lifetime preventive medication is an individual choice and we need to be practical—and humble—in our approach to informing and supporting it. The true work of shared decision making has scarcely begun.

Richard Lehman is a retired GP and Senior advisory fellow in primary care, Cochrane UK, Oxford. He writes a weekly research review for The BMJ