Re: Adverse effects of statins
I applaud the Editor's decision not to retract the two papers now the subject of debate and refer the matter to an independent panel. Like Dr Newman I feel that the criticism of a minor misinterpretation of figures does not warrant retraction. There are a number of reasons for this.
1. I am in no doubt, both personally and from the reported experience of my patients, that statin side-effects are consistently under-reported. This occurs two ways; firstly, doctors airily dismiss symptoms reported by patients ("statins could not possibly cause that!"), and secondly it is unusual for well-recognised side-effects such as rhabdomyolysis or even non-specific muscle pains to be yellow-carded. In my view the potential severity of muscle symptoms justifies extreme caution.
Following the publication of an article in the "Daily Mail" detailing my personal experience (1) I was contacted by 30 patients nationwide who described statin-related sysmptoms. All the letters or emails gave clear and lengthy histories so I felt able to assess the likelihood of symptoms being satin related, and consider other diagnoses. I estimated that 18 patients definitely and 7 probably had statin side-effects (two clearly had polymyalgis, one shoulder capsulitis and one osteoarthritis of the knee). Four recorded their GP's dismissal of cause and effect and a further six recorded either GP or specialist insistence that they continue despite symptoms. Of the 18 probables, all reported relief of symptoms on cessation and two recorded recurrence on re-starting. This is, of course, a small observational study without statistical validity (influencing factors include market penetration of the "Daily Mail" to the statin target group and the propensity of people to write a response). However a recurring theme was a sense of relief from patients that they were not mad. Thus, if patients do report such side-effects, it is vital that cessation is tested.
Furthermore, if it is true that deficiency of co-enzyme Q10 predisposes to significant side-effects then it would seem reasonable to screen for this before commencing statins.
2. Critics of the anti-statin brigade routinely quote risk reduction figures that are distortions. A relative risk reduction of 50% equates to a much lower absolute risk reduction. The statistical level for significance is often taken as 5%. So if the absolute risk of an event is less than 10%, a 50% reduction is not significant and a reduction of relative risk of 50% where the absolute risk is 2% is a real risk reduction of only 1%. So while statin-backers complain of an overstatement of side-effect risk, they are often themselves guilty of just such an overstatement of benefit. Of course, patients at a high risk of coronary events do have a statistically significant benefit and I am all for the prescription of statins to that group.
3. We are still unclear of the base risk factor in coronary artery disease. Is it the level of cholesterol or low-density lipoproteins, or is this level simply an epiphenomenon for the actual risk factor? If we look at coronary disease (CD) risk in rheumatoid arthritis (RA) we find that patients with untreated RA have a substantial risk of CD - possibly as bad as diabetes. This risk returns to normal if the RA is controlled. But serial cholesterol measurements show that cholesterol levels actually rise with RA remission. Add that to the apparent finding that statins may be beneficial in RA we are left with an unresolved paradox, for which one explanation is that it is not the cholesterol level that is important, but something else (perhaps the levels of inflammatory mediators). In other words, statins may not work because they lower cholesterol, but because they do something else, and measuring cholesterol may be irrelevant.
4. Given the costs of blanket statin treatment to the over 50s, or those with fasting cholesterol levels over whatever is deemed to be risky (though, in normal range terms, it is often normal) I consider it essential that a full cost-benefit analysis is done to balance prescribing costs against CD treatment costs. As another correspondent has already pointed out, we are not saving 50,000 lives a year - we are postponing 50,000 deaths. So the analysis on-costs should include the costs of treating subsequent diseases (dementia, stroke and cancer, for example). The cost per at-risk patient may well be acceptable but the global cost of universal treatment may not. I have seen no evidence either way. Given the financial problems of the National Health Service, continuing without such an analysis is financially irresponsible.
I find it surprising and disappointing that Professor Collins has chosen to raise his concerns in the media rather than through published correspondence in the British Medical Journal. To sensationalise the argument outside proper scientific channels will fuel patient concerns rather than allay them. I would also like to know whether Professor Collins has directly or indirectly received funding from any manufacturers of statins -which, of course, requires a conflict of interest statement in the medical, though not the popular press.
(1)Bamji AN. The hidden (and painful) cost of statins. Daily Mail, February 3rd, 2009
Competing interests: I suffered significant statin musculoskeletal side-effects which lasted for some years after cessation