Over the last decade or two, it seems that increasing pressure has been put on us to have our cholesterol levels measured, and to do something about them if these turn out to be ‘raised’. Elevated cholesterol levels in the bloodstream is often said to be a potent risk factor for so-called ‘cardiovascular’ disease – something which can ultimately lead to unwanted and potentially fatal events such as heart attack and stroke.
From a conventional medical perspective, the mainstay treatment for reducing cholesterol are known as the ‘statins’ which include atorvastatin (Lipitor), rosuvastatin (Crestor) and simvastatin (Zocor). A huge stash of cash has been made out of these drugs, but is their life-saving reputation deserved?
Before we get delve into this subject in depth, we must first get clear on the two fundamental ways statins may be used the prevention of cardiovascular disease. One way is to prescribe statins to people who have no evidence of existing cardiovascular disease. This type of approach is described as ‘primary’ prevention. Statins can, of course, be used in individuals who have been diagnosed with cardiovascular disease. For instance, they may be known to have narrowing of the vessels around the heart (heart disease), or may even already have had an event such as a heart attack or stroke. Giving statins to such individuals is described as ‘secondary’ prevention.
What is the relevance of making this distinction? Well, individuals with a history of cardiovascular disease, compared to essentially healthy individuals, are at a much higher risk of cardiovascular complications such as heart attack and stroke. As a result, they are generally much more likely to benefit from whatever benefits statin drugs may have to offer.
Studies have found that in secondary prevention, statin drugs reduce the risk of death from cardiovascular events such as heart attacks and strokes. This translates, crucially, into a reduced risk of overall risk of death too. Scientists have generally assumed that these benefits also apply to the primary prevention setting, but do they?
In this week’s copy of the Lancet, an editorial examined this issue in some depth . Its authors present the results of their own review of a total of 8 predominantly primary prevention trials . This showed that statin therapy was NOT effective in reducing overall risk of death. The study found that risk of cardiovascular events such as heart attacks and strokes were reduced by statin therapy, but that this amounted to a real reduction to the tune of 1.5 per cent. What is more, 67 individuals would need to be treated for 5 years for just one ‘event’ to be prevented. One of the most startling findings of this review was that there was no apparent benefit seen in women (of any age) nor in men over the age of about 70.
These results are further weakened by the fact that 8.5 per cent of the individuals in these studies were actually in the secondary prevention category. To get a true picture of how ineffective statin therapy and primary prevention really is, it would be necessary to analyse pure primary prevention data separately. The authors of the Lancet review do not have access to this data, but they know some people who do.
The authors draw our attention to a group of scientists known as the Cholesterol Treatment Trialists’ (CTT) collaboration who in the past have assessed data from studies which include both primary and secondary prevention . These scientists, the authors argue, have the data they need to calculate the effect of statin therapy in a purely primary setting. One wonders why they haven’t done this crucially important work.
Past events suggest this may have something to do with politics and money. Back in 2004, there was a significant lowering of what are regarded as acceptable levels of cholesterol, as recommended by a group known as the National Cholesterol Education Program (NCEP) expert panel in the USA. After its recommendations were made and taken up, it came out that 8 out of 9 members of the panel had financial links with drugs companies making statin drugs. The report’s publisher described the omission of these clear conflicts of interest as an oversight. I’ll say.
I suppose this wouldn’t matter too much if the recommendations to lower cholesterol upper limits were based on good science. The scientific basis for the recommendations made by the NCEP expert panel was in the Annals of Internal Medicine published in 2006. The authors of this review stated: In this review, we found no high-quality clinical evidence to support current treatment goals for [LDL] cholesterol. They went on to say that the recommended practice of adjusting statin dose to achieve recommended cholesterol levels was not scientifically proven to be beneficial or safe .
2004 was also the year that saw the decision to make the statin simvastastin (Zocor) available over-the-counter (OTC) in the UK. This decision seemed an odd one, bearing in mind that there is little, if any, evidence that statin therapy helps all but a small minority of the general population. Also, there has simply been no analysis at all of the likely effects of simvastatin use as an OTC medication. The Government body instrumental in the making of this decision – The Medicines and Healthcare Products Regulatory Agency (MHRA) – had previously stated that two-thirds of individuals who contributed to the consultation process had been in favour of making simvastatin OTC. That turned out to be a gross distortion of the truth ” the reality was that only about a third of individuals were in favour. The MHRA put this ‘mistake’ down to an administrative error.
Is it me, or is there something fishy going on here? What I find most curious is that in response to the Lancet editorial, which amounts to quite a damning appraisal of the basis for statin therapy, the mainstream media has reacted with deafening silence.
I think it’s great that researchers who are not in the pay of the pharmaceutical industry are prepared to ask hard questions about the presumed value of statin medication. But I also think it’s a shame that these researchers lack the funds needed to give such important work the airing it deserves.
1. Abramson J, Wright JM. Are lipid-lowering guidelines evidence-based? Lancet 2007;369:168-169
2. Jauca C, Wright JM. Therapuetics letter: update on statin therapy. Int Soc Drug Bull Newsletter. 2003;17:7-9
3. Cholesterol Treatment Trialists’ (CTT) Collaborators. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90-056 participants in 14 randomised trials of statins. Lancet 2005; 366: 1267-1278
4. Hayward RA, et al. Narrative review: lack of evidence for recommended low-density lipoprotein treatment targets: a solvable problem. Ann Int Med 2006;145:520-530