On 23 September 2004 a number of distinguished medical and health professionals wrote a detailed letter to the officials in the US National Cholesterol Education Program (NCEP) requesting an independent review of the cholesterol guidelines(1). Although this was some years ago the key points raised are just as pertinent to-day as they were when the letter was written. At the time the NCEP had just issued a new report which lowered the threshold for statin therapy. It recommended that people with a moderate risk of developing, but no previous history of heart disease should be offered statin therapy if their Total blood Cholesterol (TC) was between 100 and 129 mg/100ml(2.6-3.3 mmol/L). The significance of the new guidelines is that they extended the scope of those who would be prescribed statins to those who did not show any symptoms of heart disease (ie primary prevention). The effect of this would be to increase the number of people eligible for statin therapy which would inevitably result in a huge increase in sales of the drug. The letter noted that the credibility of the report was undermined by the fact there was a failure to disclose that 8 out of the 9 authors had financial interests with the companies that produce statins. These conflicts of interest would almost certainly affect the judgments of the authors.
With reference to the scientific justification the following points were made:
- The evidence does not support the use of statins in women with a moderately high risk of developing Cardiovascular Disease (CVD).A previous report in 2001 cited 6 different studies in support of the conclusion that statins reduce the risk of heart disease in women under the age of 65 but the letter disputes this claim. It also points out that the report actually admits that studies in support of this recommendation
“generally are lacking”
and that it
“is based on extrapolation of benefit from men of similar risk”.
In fact there was only one trial which specifically focused on women without a history of heart and the results showed that those treated with statins had a 10% higher rate of heart disease than the controls.
- The evidence does not support the use of statins in men or women over the age of 65, which is when most deaths do occur. Again the earlier report claimed that there were 9 different studies which provide evidence that statin therapy effectively reduces the risk of developing heart disease in people over 65 who have not suffered from the disease previously. The letter challenges this conclusion and states that:
“not one of the nine studies provided significant evidence that statins protect senior citizens without heart disease”.
- In fact there was only one study called PROSPER which looked specifically at this issue which according to the NCEP report provides support for:
“the efficacy of statin therapy in older, high-risk persons without established CVD.”
However the letter comments:
“In fact, the evidence shows just the opposite. Those treated with a statin did not experience significantly fewer heart attacks and strokes. But they did develop 25 percent more new cancers than the people in the control group (statistically significant). Although the published study does not divide the new cancer diagnoses into primary- or secondary-prevention patients, it is worrisome that the risk grew each year a statin was taken, so that by the fourth year of the study there was more than one additional case of cancer for each 100 patients taking a statin for a year.To downplay this increased cancer risk, the NCEP report ….data are merged with data from previous statin clinical trials in a meta-analysis, the increased cancer risk is reduced to insignificance. However, this argument was flawed because it merges studies that included younger populations (mean age < 60) with the PROSPER patients, who were all 70 and above.”
- The recommendation to treat diabetics with statins was based on one study even though there were another 3 studies which found that there was no benefit from statin therapy. Furthermore the NCEP report failed to mention that sedentary diabetics who became physically active experienced 4 times the improvement in health achieved by the statin therapy.
These are all very valid criticisms which do not appear to have been answered because the recommendations are still in force. As a consequence enormous numbers of people are being prescribed statins. It is obvious that the justification for this strategy is extremely dubious. Although it is accepted that men with heart disease do derive some benefit this is probably much smaller than most people appreciate. About 50 people have to be treated for 5 years for one to benefit(2). On the other hand there is plenty of evidence that statins may cause undesirable side-effects ranging from muscle pain to memory loss. Although the letter deals specifically with the USA, the position in the UK is essentially similar and therefore it is common practice for statins to be prescribed for women and for everyone over 65, despite the lack of any reliable evidence to substantiate the strategy.
What is especially worrying is the way in which the evidence has been manipulated and the total failure of politicians and administrators to take appropriate action.