Science journalist Maryanne Demasi completes her two-part investigation into statins, one of the world’s most profitable drugs. We know statins work. What we don’t know is information about their side effects. Many leading doctors now believe statins are being overprescribed but the raw data on statins remains concealed by the pharmaceutical companies who make them, businesses which are heavily subsidised by taxpayers around the world. This two-part series is the result of an important peer-reviewed article by Demasi. It is NOT medical advice.

Statin Wars Part 2 — Read Part 1 here.

Have we been misled?

Yesterday, I reported on renewed calls for greater transparency from a growing number of doctors seeking access to undisclosed data on statin side effects.

These calls have prompted fresh concerns about the authenticity of the statin data and led to bitter divisions within the medical fraternity.

Proponents describe statins as one of “the most important advances in medical history and have prevented untold heart attacks and strokes”Detractors say statins “serve no purpose in lowering cholesterol to prevent cardiac problems” and even label them “unnecessary and toxic”.

Early clinical trials suggested that statins should be limited to people with advanced heart disease. Today however, a vastly different discussion is afoot.

Some UK experts suggest that everyone over the age of 50 should be on a statin, even if they don’t have high cholesterol. Others propose we offer statins as condiments in burger outlets to “cancel out” the effects of a fast-food meal. Some suggest we screen kids for high cholesterol to identify statin recipients and there has even been discussion about putting statins in the water supply.

So how did we go from prescribing statins to a select group of people to recommending them for children, adults and anyone who consumes drinking water?

In Part 2 of this investigation, I examine how statins came to be one of the most widely prescribed drugs in the history of medicine.

My full peer-reviewed article on the subject was published in the British Journal of Sports Medicine yesterday, which you can read here.

The rise of a blockbuster drug

The cost of developing a prescription drug to gain market approval now exceeds $US2.5 billion. A more effective way to fast-track company profits is to broaden the use of an existing drug. In the case of statins, influencing medical prescribing guidelines is a convenient and powerful way to increase the use of a drug and drive higher profits.

When the US National Cholesterol Education Program (NCEP) revised its definition of “high cholesterol” by dramatically lowering the threshold, it meant millions more people would become eligible for statins overnight. The decision was not based on any new scientific data but rather the increasingly popular notion that “lower is better”.

The move sparked a furore when it was revealed that eight out of nine members on the 2004 NCEP guideline committee had direct financial ties to statin manufacturers.

“eight out of nine members on the

2004 NCEP guideline committee had

direct financial ties to statin manufacturers”

Then, in 2013, the American College of Cardiologists (ACC) and the American Heart Association (AHA) changed their guidelines to reflect a person’s “calculated risk”. Again, it meant that millions more adults would be prescribed statins, most of whom were older people without heart disease and for whom the evidence for benefit was lacking.

Shortly after, the UK’s National Institute for Health and Care Excellence (N.I.C.E) announced its plan to slash the “calculated risk” threshold for prescribing statins by half. N.I.C.E’s deciding panel comprised 12 members, eight of whom had financial ties to manufacturers of cholesterol-lowering drugs. UK doctors vigorously objected to the changes saying it was “not evidence-based” and could lead to the “medicalisation of healthy people at the cost of more needy, unwell patients”.

In addition, the “risk calculators” which a doctor uses to assess a patient’s risk of heart disease and determine whether or not to prescribe a statin, is likely to be inaccurate. A study examined five risk calculators and demonstrated that four, including the new AHA-ACC-risk calculator, showed the over-estimation of risk could be as high as 115 per cent, giving rise to concerns about the undisciplined over-prescription of statins.

This phenomenon is dubbed “diagnosis creep”, a process which – by simply changing the definition of a disease or lowering the threshold of risk – healthy people are turned into patients overnight. Doctors are now raising awareness to reduce the harms of over-diagnosing and over-medicating people, in a campaign called “Too Much Medicine”, upon which I previously reported.

Conflicts of Interest

In the 1980s, when US President Ronald Reagan came into office and slashed government funding to the National Institutes of Health, it left a gaping hole for private industry to move in.

Drug manufacturers sponsor the vast majority of statin trials. Notably, one major non-industry funded study on statins actually showed that the drug had no benefit in reducing death or coronary heart disease in healthy people. A recent Cochrane review showed that sponsorship of drug trials by the drug manufacturer leads to more favourable results and conclusions than sponsorship by other sources.

Peter Goetzsche

There is also concern about the influential views of eminent doctors who are on the payroll of drug companies. These doctors might argue that “science is science” and that it doesn’t matter who pays for it. But others disagree.

“When drug industry sponsored trials cannot be examined and questioned by independent researchers, science ceases to exist and it becomes nothing more than marketing”, says Professor Peter Gøtzsche from the Nordic Cochrane Collaboration.

Robert DuBroff

“Reputations and big money are at stake. Not only are financial conflicts of interest at play, but the behavior of many statin proponents exemplifies the concept of confirmation bias – seeing what you want to see and ignoring what you do not”, says US cardiologist Professor Robert DuBroff from the University of New Mexico.

Underplaying the risks

There are simple ways to design a clinical trial which has the effect of minimising the harms of the drug. One example is the use of a “run-in” period, such as in the Heart Protection Study. All participants took a statin for six weeks prior to the commencement of the trial, after which time, 36 per cent of people were excluded from the trial.

Removing a third of participants from a trial, presumably because they were not compliant or experienced unacceptable side effects, would grossly underestimate the actual rate of side effects recorded during the trial. This may explain why the rate of side effects in statin trials is significantly lower than the rates reported by doctors in “real world” observations.

In the past few years, statins have been linked to a small but significant increased risk of type-2 diabetes. It has led to a safety label change on statins by the US Food & Drug Administration and has sparked multi-million dollar class actions against the statin manufacturers.

Statistics, statistics

Often when you hear about the benefits of statins, you may be told they reduce your risk of having a heart attack by 30 per cent or more. Others say this may be misleading.

For example, a study claimed that taking Lipitor reduced the risk of heart attack by 36 per cent. It led to an impressive advertisement for Pfizer’s product, featuring a trustworthy doctor.

Lipitor ad

However, when you examine the study closely, you find that taking a statin reduced the risk from 3.1 per cent down to 2 per cent (see Table 4).  So yes – technically – the number was reduced by 36 per cent, but the “absolute” reduction in risk was only 1.1 per cent which sounds less impressive. For this reason, drug companies will avoid quoting absolute risk numbers in their marketing and advertising campaigns.

When prescribed a statin, most people want to know how long it will extend their life. Will it be ten years, or five years? A group of researchers attempted to answer this question by re-analysing the trial data on statins. The study demonstrated that, when people who took a statin every day for five years, it only increased their life expectancy by between three to four days.

Statin proponents were quick to defend their position claiming that the benefits would have accumulated if the statins were taken beyond five years. However, it is disingenuous to claim that the benefits of statins accumulate in the absence of accumulating side effects. In fact, the longer the duration of a trial, the more likely it is that other diseases, which take longer to develop, would emerge such as cancer and neuro-cognitive dysfunction.

In conclusion

Detailed in this report are some of the factors which have influenced the over-prescription of statins. Clinical trials use run-in periods to exclude people who cannot tolerate statins. They exclude people on other medications, they exclude very elderly people, the vast majority of trials are funded by industry and no independent researchers are permitted to scrutinise the raw data which are being held by the CTT Collaboration. Hence, doctors might need to remain inherently sceptical when prescribing these medications to healthy people, at low risk of heart disease, unless they can be sure the benefits outweigh the harms. The campaign for greater transparency in medicine is therefore of vital public interest.

Read Maryanne’s full peer-reviewed article published yesterday in the British Journal of Sports Medicine here.

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Dr Maryanne Demasi

 

Dr Maryanne Demasi is an investigative medical reporter with a PhD in Rheumatology.

You can follow her on Twitter @MaryanneDemasi.

 

 

 

Dear Pfizer, pay it back