Currently there is widespread use of statins which is justified on the grounds that those who receive regular treatment will have a reduced risk of developing heart disease. Ideally there should be thorough evaluations which demonstrate the extent of the benefits as well as comprehensive knowledge of the adverse side effects which may arise. However in the real world, doubts persistently arise about both of these sides of the equation.
About 2 years ago, NICE decided to go ahead with its proposal to recommend that those with a 10% risk of developing heart disease should be considered for treatment with statins. In an article in the BMJ, Professor Mark Baker, the director of the Centre for Clinical Practice at the NICE, stated that 77 people would need to take statins for 3 years for one to benefit (1). He justified this on the grounds that with blood pressure lowering drugs, 104 patients would have to be treated for one to benefit.
The figures quoted only apply to those who have heart disease in the past. However when statins are used for primary prevention, which effectively is what is being proposed, there is no benefit in terms of improvement in life expectancy.
I strongly suspect that most people who are being advised to have statins, usually very strongly, they would be very surprised at that their personal chances of a benefit is so small. About a year ago, Sir Rory Collins who is a powerful advocate of statins and runs an organization at the University of Oxford to analyse drug company data on statins admitted that the information on side effects was incomplete (2). In particular they had ignored reports from doctors and patients of serious muscle pains, diabetes, cataracts, memory loss, brain fog and declining libido.
With this background a recent critical review by Michel de Lorgeril and Mikael Rabaeus provides valuable insight into the relevant background (3).
One of the fundamental points made by these authors is that there are serious doubts about the reliability of Randomized Controlled Trials (RCTs) to evaluate drugs prior to 2005/6. This arose because of the scandals related to a number of drugs including Vioxx. This was a painkiller produced by Merck, which was responsible for at least 55,000 deaths and resulted in compensation of almost $5 billion. As a consequence new regulations were introduced in both Europe and the USA which required much greater transparency about the investigations into drugs in order to gain approval. The authors of this review conclude that we cannot be completely confident of the validity of any data on statins which originated before 2005/6.
In the light of this, they have considered the trials which have been conducted since the new regulations came into force. It was decided that the only trials which were acceptable were those in which the statin was tested against a placebo. There were only 4, all of which used rosavustatin, which complied with this criterion, namely:
- The JUPITER trial, in which the patients were considered free from cardiovascular disease but had a rather moderate risk of cardiac death.
- The CORONA trial, in which patients were survivors of a previous acute myocardial infarction (AMI) and were at high risk of AMI recurrence and cardiac death.
- The GISSI-HF trial, in which all patients had cardiac dysfunction, 50% had a previous AMI and 50% suffered another heart disease.
- The AURORA trial, in which patients presented with severe renal failure. 50% had previously suffered an AMI or other heart complications.
This trial has been the subject of considerable controversy because of the fact that it was stopped early. This is indirect conflict with accepted best practice because the effects may vary with time. In particular, the impact may diminish as the trial progresses. I have discussed the JUPITER trial in an earlier blog (4). The publication of the results was an absolute shambles. There were errors in the initial mortality data released and there were at least 5 different versions of the cardiovascular mortality reported. It turned out that there was no difference between the placebo and the statin groups in cardiovascular mortality. There was actually a small difference in the all-cause mortality but this was not validated by the FDA statisticians. It is not possible for independent researchers to investigate this any further because the raw clinical data have not been released by the drug company. There was also a significant increase in the incidence of Type 2 Diabetes (T2D) in those treated with rosavustatin.
Although those on the rosavustatin showed a marked reduction in blood cholesterol levels, there was no clinical benefit whatsoever, especially in terms of survival. There was no difference between the groups in the incidence of cardiac death, AMI, and other nonlethal ischemic complications. In an attempt to explain the failure it was postulated that the statin would not be expected to protect “elderly heart-failure” patients, presumably on the grounds that the damage had already progressed too far. However when the data were analysed according to age and degree of cardiac dysfunction at the outset, no benefit was found in any cohort which effectively destroys that excuse.
This trial produced exactly the same results as the CORONA one and confirmed that rosavustatin did not provide any benefit for those who already suffered from heart disease.
These patients with renal failure have a high risk of an AMI and so would be expected to benefit from treatment with a statin. In fact, the results provided further confirmation that there no clinical benefit from the statin treatment despite a marked reduction in the blood cholesterol level.
It is now abundantly clear that we do not have good quality research to justify the use of stains for either primary or secondary prevention. Even though new regulations have been introduced the degree of transparency is still not adequate and the drug companies continue to deny access to the raw data by independent researchers. It is essential that this happens if we are to be confident in the conclusions which are crucial for decisions made by health professionals and governments on statin usage. The review summarises the present position as follows:
“The obvious final conclusion for physicians is that the present claims about the efficacy and safety of statins are not evidence-based.”
In this blog I have only been able to highlight some of the key points in the review, which is very well worth studying carefully, especially if you are being advised to be treated with statins.