Fooling Doctors and Distorting Science

The Statin Trials

        These days it is hardly possible to leave a doctor’s surgery without a prescription for a statin. We are told statins save lives. But is it true? Or could the entire medical profession have been hoodwinked by clever sales techniques by the drug industry? Let’s look at the evidence.

        Since the QOF (Quality and Outcomes Framework for GPs) was started in 2005, 3 million people have been put on statins at the cost of several billion pounds (at one time one statin alone, atorvastatin, was costing the NHS over 300 million pounds annually). Did this huge outlay save lives? No. In fact life expectancy went gone down over this period.

        There have been over 30 industry-funded trials of statins, all of which have purported to show some benefit from statins (usually a very small one). We will look at some key studies later. There has been just one independent study called the ALLHAT-LLT study (funded by the US government).  This showed statins gave no benefit. I know which study I believe.

        Guidelines on statin are written by experts who nearly always have strong links with pharmaceutical companies. They have typically recommended aggressive use of statins. However the independent Cochrane Collaboration looked at exactly the same evidence and found there would be no benefit in primary prevention with statins (that is giving statins to people without heart disease).

         An independent review of statin trials since the guidelines for trials were tightened (slightly) in 2005 has been done by Dr Michel de Logeril (one of the few experts with no links with the pharmaceutical industry). He found that the trials “showed unambiguously that statins have no benefit in secondary prevention (those with heart disease) and their use in primary prevention was highly debatable”. In other words, they were next to useless. He also found high dose statins produced no better results than low dose statins.

It’s interesting and sometimes amusing to look at some of the key trials and see how much the hype differs from the reality.

THE 4S TRIAL

The first and most successful statin trial ever.  It used simvastatin.

THE HEADLINES: There is no longer any doubt that the benefits of treating cholesterol in patients who have had a heart attack.

THE REALITY: 150 people would need to be treated for one year to prevent one heart attack. 149 other people would be exposed to adverse effects which are far from insignificant.

OTHER POINTS: There was no overall mortality benefit for women who had heart attacks (this is true of all other statin trials).

The dose of simvastatin didn’t make any difference (a point that comes up later and has been completely ignored).

THE WOSCOPS TRIAL

This was with pravastatin.

This was a trial of those at high risk of heart disease.

HEADLINES: This landmark study showed for the first time that statins reduce fatal and non-fatal heart attacks in those without heart disease.

THE REALITY: The data showed that by taking a statin, men at high risk of heart disease, would have a 91.4% chance of living 5 years whereas without it would be 90.6%. In other words the benefit was miniscule.

OTHER POINTS: There was no difference in the death rate (all-cause mortality) whether patients took a statin or not. If there is no difference in the death rate it means the drug has no value to a patient. Most statin trials show this same lack of mortality benefit.

THE HEART PROTECTION TRIAL

This also used simvastatin

HEADLINES: The world’s largest cholesterol-lowering trial reveals massive benefits for high-risk patients.

THE REALITY: There was a tiny 0.36% reduction in mortality. To save one life, 200 people would have to take the statin for 5 years (and 199 would be at risk of adverse effects for that time).

        The next two trials are the most interesting. The claims they make are virtually the exact opposite of what they found. It shows how the truth in drug trials can be distorted beyond all recognition.

THE JUPITER TRIAL

With rosuvastatin.

This was a primary prevention trial of those without heart disease. It launched the drug rosuvastatin.

HEADLINES: It’s breath-taking, it’s absolutely paradigm-shifting. Statins reduce heart attack death rate by close to 100%.

THE REALITY: There was precisely the same number of deaths from heart attacks and strokes in those that took the statin as those that took the placebo (12 deaths from heart attacks and strokes in both groups). This damning evidence was carefully hidden in the small print of the paper.

OTHER POINTS: There were 54 extra cases of diabetes in those taking statins (a 25% increase compared to those taking placebos).

THE SEARCH AND IDEAL STUDIES

Comparing high with standard dose statins.

SEARCH Compared high dose simvastatin (80mg) with low dose simvastatin (20mg) and IDEAL compared standard dose statin (atorvastain 80mg) with low dose stain (simvastatin 20mg or 40mg)

HEADLINES:

 SEARCH: There is clear evidence that lowering of LDL cholesterol reduces the risk of vascular events and intensive lowering reduces the risk further.

 IDEAL: We now have very clear evidence that patients will benefit from more intensive cholesterol lowering.

THE REALITY:

 SEARCH: There was no significant different between intense and standard therapy, no different in heart deaths, no difference in heart events, no difference in strokes and no difference in total mortality. The only thing that was different was rhabdomyolysis (a severe muscle injury which can sometimes be fatal) which was seven times higher in the high dose group.

IDEAL: No statistical difference was seen in all-cause mortality, cardiovascular mortality and non cardiovascular mortality.

In fact, these two trials confirmed the dose of statin made no difference but side-effects were more on the higher doses. My take on this is that the lowest dose of statin should be given.

To sum up: the benefits of statins are vanishingly small (pooled data has found the life expectancy benefit of statins to be 3 to 4 days), the cost astronomical, the hype unbelievable and the side-effects far from minor (memory loss, diabetes, personality change, muscle pain, impotence). See the Statin leaflet for more details on adverse effects. In addition simple life style measures give superior benefits without any of these adverse effects (see Food, Lifestyle and the Heart leaflet).

But this is not just about statins. It is about how easily the medical profession can be fooled by drug trials.

  I am not blaming doctors here. They do their best and most genuinely believe they are helping us by prescribing statins. But there are a hundred different ways that drug companies can manipulate statistics to spin their products and they are not easy to spot. Doctors never had a chance.

But this is also about future of medicine. Medicine has to be based on unbiased scientific facts. If not, it is no longer credible as a science. If doctors make their clinical decisions on dodgy data then the prescriptions patients receive will be equally dodgy. This is bad news for doctors and patients alike.