'Conclusive' Proof Statins Are Safe and Effective

A recent study published in The Lancet has been reported (by the journal) as providing conclusive proof that statins are safe and effective in the long-term. The Lancet also produced a podcast on their website and published a commentary to accompany the study.

The results of this study, along with the associated podcast and commentary have been presented in a way that is extremely favourable to statins. However, there is an obvious fundamental flaw with this study that, in my opinion, has not been adequately discussed.

The new study relates to a follow-up of the Heart Protection Study (HPS), which was a statin clinical trial that ran for just over 5 years. At the end of this study the researchers continued to monitor the participants for a further 5 years. 

During the follow-up period, increasing numbers of people who were in the original placebo group started to take a statin. By the end of the study, the number of people taking a statin in each group was the same. 

The table below shows how many people (as a percentage) were taking a statin in each group.

 

Obviously, the study was no longer comparing a statin against a placebo – it was comparing statins against statins. Just to make it even more confusing; we do not even know which statin people took during the follow-up period and at what dosage.

This did not stop the researchers describing the results of this study as definitive evidence in favour of statins. 

Most doctors who prescribe statins will not have the time to read the full study and will have to rely on the summary and the podcast. This will leave them with an interpretation of these results that is heavily skewed in favour of statins.  

As far as I am concerned, the fact that just as many people in the placebo group took a statin is enough to nullify this study. However, there are several additional issues. 

All of the people included in this study are categorised as having very high risk. Almost half had already had a heart attack, and everyone else had either other forms of cardiovascular disease or conditions that would place them at high risk.  All of the evidence from statin clinical trials has consistently shown that any 'benefit' varies greatly according to the level of risk the trial participants have. Therefore, if any statin benefits were found during this study, it is simply unthinkable to try and extrapolate this to the general population or the majority of people who take statins.

In addition, the study report and commentary describe the results in terms of relative percentages. This is a very common problem with statin clinical trials. The relative percentage is meaningless to patients and it grossly exaggerates any suggested 'benefit'. For example, in terms of vascular related deaths a risk reduction of 18% is quoted for the initial trial period. However, the real risk reduction in absolute terms was 1.7%. 

Incidently, this 1.7% risk reduction in vascular related deaths reduced to 0.1% during the follow-up period. Therefore, there is not any real evidence to support the claim that the 'benefits' of statins increase if a person starts taking the statin earlier in life. 

It is also worth mentioning that statins have a wide range of adverse effects (some very serious) that were not included in this study. 

References:

Reuters: Cholesterol drugs safe, even after a decade of use. 23 November 2011

MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20 536 high-risk individuals: a randomised placebocontrolled trial. Lancet 2002; 360:7-22

Heart Protection Study Collaborative Group. Effects on 11-year mortality and morbidity of lowering LDL cholesterol with simvastatin for about 5 years in 20 536 high-risk individuals: a randomised controlled trial. ; published online Nov 23.

Kohli, P and Cannon, CP Statins and safety: can we finally be reassured?Lancet 2011;  published online Nov 23

At Last, the Tide has Turned!

Statins have been in the media a lot again this week and finally at least some of the facts are starting to get out. It has all been prompted by a review conducted by the Cochrane Collaboration. This review concluded that for many people who take statins, the risks for adverse effects outweigh any benefits.

This will be of no surprise to anyone who has looked into this subject, and the media reports do not go far enough, but at least some of the issues regarding statins are now starting to reach the general public.

The news reports do not go far enough because they still suggest that cholesterol is a risk factor for heart disease. After all this time it still absolutely amazes me that so many doctors have not bothered to take even the most casual look at the evidence.

British Heart Foundation Continues to Support Statins

Here is the latest headline from the British Heart Foundation (BHF):

“Research by BHF-funded scientists has shown that when it comes to cholesterol, ‘lower seems to be better’ for protecting us against heart attacks... The researchers looked at the effects of increasing the dosage of statins, a medicine that reduces cholesterol. They showed that a bigger drop in cholesterol – from more intensive treatment with statins – cut risks even more.”

This refers to a study just released in the Lancet. This study, and the media hype that the BHF have created about it, is nothing more than an attempt to confuse and mislead people.

If you read the headlines and the summary report you could certainly be forgiven for thinking that statins are wonder drugs and cholesterol really is humanity’s nemesis. This study did indeed find a reduction in heart attacks associated with more intensive use of statin drugs. However, there are at least four major reasons why the results are misleading.

The first reason is that the reduction in risk quoted in the interpretation of the study refers to a reduction in LDL cholesterol that is not normally seen in real life. This exaggerates the perceived benefits.

The interpretation refers to reductions in LDL levels of 2-3 mmol/l. The authors state that this reduction in LDL cholesterol would reduce the risk of a vascular event (such as a heart attack) by 40-50 percent.

Well, LDL cholesterol is typically around 2-3 mmol/l anyway, so the suggestion that it could be reduced by 2-3 mmol/l is nonsense – most people would have to be clinically dead to achieve this drastic reduction. So, the suggested risk reduction is completely academic and for most people could never happen.

The second reason is that, as usual, relative percentages are used instead of absolute percentages. This problem is ubiquitous in statin clinical trials and I have commented on it many times before. The risk reductions of 40-50 percent are relative percentages, which can only mislead people. In real terms, the percentages come down to single digits or less.

The third reason is that, as usual, the issue of deaths from all causes is not addressed. Statins can reduce the risk of suffering a heart attack or other cardiovascular event, but at the same time, these drugs can also increase the risk of dying from other causes, and overall, there is usually no net benefit.

There is not much point in taking an expensive medication if the risk for one disease is reduced at the cost of increasing the risk for another disease within the same time period.

I called the BHF today and asked them for the data concerning deaths from all causes. The press office said they didn't know, but they did kindly send me the full report for the study.

In this trial, the risk of dying from any cause was reduced from 2.3 percent to 2.1 percent. So, in real terms, the benefit of more intensive statin use equates to a risk reduction of just 0.2 percent.

But even this meagre 0.2 percent risk reduction may not be experienced by real people who take statins. This issue relates to the fourth problem with this study.

The forth reason why the results are misleading is that the analysis did not distinguish between people at a lower risk for a heart attack and people at a higher risk.

Around 7 million people are taking statins in England alone, and in America it is estimated that more than 20 million people may be taking them. The vast majority of these people are taking statins for primary prevention. This means that they do not have cardiovascular disease but are given the medications in the hope of preventing future disease.

To date, there is no convincing evidence that statins provide any net benefit to people when they are taken for primary prevention - they do not reduce the overall death rate. This was the conclusion of the latest analysis in the Archives of Internal Medicine.

The analysis that the BHF are supporting includes data from higher risk groups - the results do not represent the majority of people who currently take a statin.

Medical Director of the British Heart Foundation Supports Cholesterol Hypothesis

Yesterday there was an article in the Daily Mail newspaper titled Statins: Should You Be Taking Them?

Professor Peter Weissberg attempts to present a case for the use of statins. Professor Weissberg is the medical director of the British Heart Foundation.

The first thing to notice about Professor Weissberg’s comments is that he avoids mentioning any actual data for the benefit of cholesterol-lowering statins.

There are numerous comments made by Weissberg that I would take issue with. For instance, he states that the average cholesterol level in the UK is:

 “high compared to, say, China, where it is 3.2mmol/l and where there are significantly fewer cases of heart disease”

While this comment about China is correct, it should be looked at in the context of other data published by the British Heart Foundation.

 

For example, the average cholesterol level for women in the U.K. is the 12th lowest on a scale of 45 countries. A similar pattern is found for men in the U.K., who are the 15th lowest on the same scale of 45 countries. Despite this, the U.K. of course has one of the highest rates of heart attacks in the world.

Cholesterol levels in the UK have been declining for some time. For example, between 1994 and 2006 the percentage of men aged 65 to 74 with ”high” cholesterol decreased from 87 percent to 54 percent. Despite this, the rate of coronary heart disease for this age group stayed about the same. Other age groups have experienced an increase in the rate of heart disease as the number of people with “high” cholesterol has decreased.

Ticino in Switzerland has the highest cholesterol level of all regions studied in the World Health Organisation MONICA project. The region has the highest percentage of men with cholesterol levels above 7.8mmol/l. They eat more saturated fat than men in the U.K. Yet they have one of the lowest rates of heart attacks. 

Men in Moscow, have one of the lowest rates of high cholesterol, but they have a much higher rate of heart attacks than men in Ticino. 

Men in Glasgow, U.K. have lower cholesterol levels than men in Ticino, but their rate of heart attacks is more than two and half times greater. 

All of this data is published by the British Heart Foundation and is available from their statistics website www.heartstats.org. 

Some time ago the British Heart Foundation published a booklet about lowering cholesterol. This booklet contained a diagram showing that 46 percent of people in the U.K. who had died of heart disease had 'high' cholesterol. Of course, this means that more than half of the people who die of heart disease do not have “high” cholesterol: they have low cholesterol.

Should Drug Companies Be The Only People Doing Research?

There was a discussion recently in the British Medical Journal (BMJ) about the many problems associated with drug companies doing most of the research on their own products. Thankfully, these issues are now becoming more widely known and they were briefly discussed on BBC Radio 4.

The discussion was between Ben Goldacre and Vincent Lawton.

Ben Goldacre is a doctor who writes the Bad Science column in the Guardian newspaper. Personally, I do not always agree with his analysis of some issues but on this occasion he has hit the nail squarely on the head.

In the BMJ, Ben Goldacre provides a brief summary of the main problems associated with drug companies sponsoring most of the research (1). He clearly explains how doctors can be misled by pharmaceutical companies not publishing the negative research finding associated with their drugs. He also describes how these companies can publish the same positive study several times (each in a slightly different way but using the same data) – the positive results from one trial then create the impression that several different positive studies have been done.

In the same BMJ article, in order to counter these arguments, Vincent Lawton provides a case for drug companies being in the best position to do the research (2).

Vincent Lawton admits that the current system is not perfect, but goes on to vaguely suggest that things will get better by drug companies regulating themselves better. He also suggests that research being done by drug companies leads to greater innovation.

This greater innovation, in my view, is difficult to accept. It is well known that the pharmaceutical industry is trying to deal with a crisis – in recent years there have been a distinct lack of innovate drugs. A large number of commentators have raised this issue. For example, the statement below is taken from an official journal of the Canadian College of Family Physicians:

“Most “new” products brought to market since the 1990s have not substantially improved on the medical benefits provided by older, less costly drugs whose risks were well known. These new products are “me-too” drugs.....Most do not represent genuine therapeutic advances or meet those needs perceived by family physicians. They do, however, increase drug consumption. Technologic innovation does not equal therapeutic progress (3). “ 

This lack of meaningful innovation has led to drug companies having to get more people to take existing drugs. They do this by creating a society of the worried-well and by making people fear suggested risk factors (like cholesterol).

So who is Vincent Lawton? You might think that he works for a large pharmaceutical company. No, he is actually an executive director of the MHRA – the UK organisation that decides whether or not drugs should be approved for use.

Why does a director of the MHRA have such a favourable view of the pharmaceutical industry? Do potential conflicts of interest exist between the MHRA and pharmaceutical companies?

The MHRA recently conducted a safety review of cholesterol-lowering statin drugs (4). It concluded that statins are associated with a greater risk for depression, sleep disturbances, memory loss, sexual dysfunction, and lung disease. However, statins have been shown to also increase the risk for other more serious problems.

Studies have shown that statins increase the risk for type 2 diabetes and they also increase symptoms associated with heart failure. There are also unresolved questions concerning statins and cancer.

The recent MHRA safety review should have provided an opportunity to investigate these risks but there was no mention of the 3 more serious conditions anywhere in their report. 

References:

1. Goldacre, B. Is the conflict of interest unacceptable when drug companies conduct trials on their own drugs? Yes. BMJ 2009;339:b4949 

2. Lawton, V. Is the conflict of interest unacceptable when drug companies conduct trials on their own drugs? No. BMJ 2009;339:b4953 

3. Biron, P et al. Pharmas-co-dependence exposed. Can Fam Physician 2007;53(10):1635–1637 

4. MRHA Public Assessment Report, Statins: updates to product safety information Nov 2009