The National Institute for Health and Care Excellence (NICE) has recently proposed new guidelines for the treatment of healthy people with statins. If the new guidance is confirmed it will mean offering statin treatment for the primary prevention of CVD to people who have a 10% or greater 10-year risk of developing CVD. As a consequence the number of people eligible would increase from 7 million to 12 million.

It is evident that these proposals have not met with universal approval. In fact there is considerable opposition, which is illustrated by a letter to NICE (copied to the minister for Health Jeremy Hunt) from a number of doctors, including Sir Richard Thompson, president of the Royal College of Physicians and Dr Clare Gerada, a former chair of the Royal College of GPs (1). This letter has spelled out several issues of concern if the proposal is implemented.

The letter contends that the benefits in a low risk population do not justify putting approximately five million more people on drugs that will then have to be taken lifelong. The authors point out that with one particular statin, atorvastatin, there has never been any evidence that it reduces all-cause mortality when used for primary prevention.

When it comes to adverse side-effects, there was very little difference in the incidence between the control and statin-treated groups. However the results for the most important trials vary from 2.7% to 80.4%. While there may be some differences in the way the information has been obtained, the fact remains that the variation is enormous and raises very serious doubts about the reliability of the data. As the letter says:

“it is difficult to understand how statin related adverse events, and placebo related adverse events can mirror each other so precisely, whilst the absolute rates can vary thirtyfold (almost three thousand per cent).”

The authors also express concern that the data on which NICE bases its’ position originates almost entirely from studies funded by the pharmaceutical companies. This information is not available to independent researchers. NICE cites the conclusions of the Oxford Cholesterol treatment Trialists Collaboration (CTT), which has commercial agreements with pharmaceutical companies that prevent it releasing the data to any other researchers. In fact the CTT study has been subject to severe criticism which concludes its’ approach is fundamentally flawed (2). This would explain why the conclusions differ from other studies that have not been able to worthwhile advantages linked to statin usage The only non-industry funded trial of statins found that there was NO BENEFIT in terms of reduced mortality.

In the industry sponsored trials, those who cannot tolerate statins are excluded which means that those who participate are not an accurate representation of the population, which actually take the drugs in the real world. Hence these trials probably underestimate adverse effects such as myopathy or cognitive impairment. In addition they are unlikely to detect interactions with other drugs.

In one trial, in which patients were given either simvastatin or pravastatin it was found that 40% of women reported reduced energy or fatigue with exertion. Since increasing physical activity, especially in those who take little exercise, is an important way of reducing the risks of CVD, this adverse effect is extremely counterproductive.

In the Women’s Health Initiative study, which involved 153,840 post=menopausal women aged between 50 and 80 years old, it was found that statins were associated with a 48% increased risk of developing diabetes. It seems likely that the use of statins has made a contribution to increased incidence of diabetes in both the USA and the UK.

When efforts are made to study erectile dysfunction it is found that the incidence in statin users is about 20%, yet this is a condition not usually recorded in standard trials.

Many GPs are opposed to the proposed new guidelines and the letter makes clear that they will be placed in an invidious position if they are required to adopt procedures which they consider inappropriate.

In a survey of 511 GPs conducted by the magazine Pulse it was found that 57% oppose the plan to lower the current 10-year risk threshold for primary prevention from 20% to 10 (3). Only 25% would support the proposals. It was also highly significant that 55% would not personally take a statin or recommend a family member to do based on 10% risk.

If GPs are expected to introduce procedures which they believe are not justified there is a real risk of a damaging split within the profession, and a loss of confidence among the public, who are likely to recognise increasingly that GPs are being asked to prescribe statins despite feeling it is inappropriate.

Finally the letter highlights potential conflicts of interest, noting that 8 members of NICE’s panel of 12 experts for its latest guidance have direct financial ties to the pharmaceutical companies that manufacture statins. In addition some members of the guidance panel are involved in the development of next generation cholesterol-lowering drugs which are more expensive. It is self-evident that the lowering of the threshold will expand the potential market for these drugs.

At Oxford University, the CTT is being done at the Clinical Trials Service Unit (CTSU), which has carried out many very large studies on statins with support from the pharmaceutical industry. Over the years the CTSU has received funding of many hundreds of millions of pounds. In one project alone the university was awarded a grant of £96 million.

It is blindingly obvious that there are genuine doubts about the validity of the NICE guidance. It is inevitable that the industry will attempt to highlight the benefits of any drug, while at the same time the adverse side-effects are being played down. Although this may be understandable, it is certainly not ethical. What is totally unacceptable is the stance taken by NICE which apparently just accepts the data and the approach presented by the industry without question. If NICE was doing its’ job properly which I assume must be to protect the public and to ensure that we are getting value for money, then surely it should be subjecting the case for any drug usage to very thorough scrutiny. There is absolutely no evidence that this is happening. If anything the reverse is true and NICE comes across as the lapdog of the industry.

 

REFERENCES

  1. http://www.nice.org.uk/media/877/AC/NICE_statin_letter.pdf
  2. http://vernerwheelock.com/?p=385
  3. http://www.pulsetoday.co.uk/clinical/therapy-areas/cardiovascular/majority-of-gps-reject-nice-proposals-to-extend-statins-to-millions-more/20005985.article#.U6AaSZRdUkQ