The Best Australian Science Writing 2015 (20 page)

On October 24, 2013, the first of Demasi's two-part program ‘The Heart of the Matter' went to air. The episodes operated like a one-two knock-out punch. The first questioned the evidence that saturated fats and cholesterol were the villains of heart disease. The second challenged the use of statins, especially in people who had not yet suffered a heart attack.

Watched by one and a half million viewers, Demasi's program triggered a firestorm. Many in the medical community considered the program had seriously distorted the mainstream view in its first episode, a criticism helped by her choice of ‘experts'.
Media Watch
, another ABC TV program, weighed in with background checks on them.

Nutritionist Jonny Bowden who claimed in the program, ‘When you look at the data, it's very clear – everything that we have been told about saturated fat and cholesterol is a bold-faced lie', turned out to hold a PhD from the Clayton College of Natural Health, an organisation with questionable credentials. Stephen Sinatra, though a bona fide cardiologist, was also found to be partial to ‘grounding', the soaking up of electrons from the Earth for better health. The two had co-authored a book titled
The Great Cholesterol Myth – why lowering your cholesterol won't prevent heart disease and the statin-free plan that will.

The second episode was roundly criticised for failing to spell out that statins have been proven beyond doubt to save lives in people at high risk of heart attacks and strokes.

Australia's National Heart Foundation was ‘shocked by the disregard for the extensive evidence'. Emily Banks, chairwoman of the Advisory Committee on the Safety of Medicines, commented to ABC news, ‘there will be people who didn't have to have a heart attack, who will die through reducing use of statins'.

It was not an idle claim – studies have shown an increased rate of death in people who discontinue their medication. Banks' concerns were realised. A National Heart Foundation survey of 1094 Australians conducted a month after the
Catalyst
program in November 2013 found ‘that more than one in five people on statins who saw the program made a change to their medication. Around a quarter of these people had previously had a heart attack'.

‘Serious journalists within the ABC were questioning how
a program like that got to air,' commented Norman Swan, presenter of the ABC's radio program
The Health Report
and regular
Cosmos
contributor.

On 12 May 2014, the ABC announced it would pull both programs after an independent commission concluded that part two (on statins) had breached the ABC's impartiality standards. Demasi remained uncowed. She said her intention had been to encourage debate and critical thinking. Though she had weakened her case by giving much of the airtime to fringe players, there's no doubt she had support from high places – including the
British Medical Journal.

In an extraordinary coincidence, two days before Demasi's first program went to air the esteemed journal published two articles that supported her take on the subject. The first was an opinion piece from Aseem Malhotra, a cardiology registrar at Croydon University in London. It took up the cause for saturated fats in an article headed, ‘Let's bust the myth of its role in heart disease', which challenged the view that a high cholesterol level is a risk for healthy people. The second, by Harvard's John Abramson and colleagues, challenged the findings of the Cochrane Collaboration. In their view the benefits did not outweigh the risks of treating non-symptomatic people with statins.

The two
BMJ
papers created their own firestorm. Malhotra was criticised for taking the same sort of fringe view on cholesterol and saturated fats that Sinatra and Bowden had expressed on
Catalyst
– one that could lead high-risk patients to stop their medications. But there was a more serious problem.

Both articles claimed the side effects of statins caused 20 per cent of patients to stop taking the drugs. The figure came from an April 2013 study published in the
Annals of Internal Medicine
led by Alexander Turchin at Brigham and Women's Hospital in Boston and his colleagues. In it, about half of the 107 835 subjects stopped taking their statins regularly. But not everyone stopped
for a particular medical reason; some people just don't like to take pills. Turchin's study was designed to explore whether the side effects from statins were serious enough to cause patients to give up on the drug.

Overall, he found 17.4 per cent of the entire group reported a side effect – the source of the figure cited by Abramson and Malhotra, who rounded it up to 20 per cent. But only 11 per cent of them actually stopped taking their pills. Turchin's study also looked more closely at a subgroup of 6500 patients who were encouraged to give statins a second try: 90 per cent of them tolerated the drug, some at lower doses or after trying a different form of statin, and were still taking statins a year later.

So in fact only 10 per cent of an initial group of refusers could not tolerate the drug. (Applying that fraction to the entire group means that only 10 per cent of the initial 11 per cent fall in this category. In other words, perhaps as few as 1 per cent of people were truly intolerant of statins.) Turchin drew a different conclusion from his findings than Abramson and Malhotra. ‘We interpret these results as a glass half-full, meaning that there are potentially millions of patients who could take statins again, and ultimately reduce their risk of heart disease', he wrote in a press release. Arguably then, the most informative reading of the study is that it was not 20 per cent who could not tolerate statins, but far fewer.

Rory Collins, the co-director of Oxford University's Epidemiological Studies unit, raised the alarm about the
BMJ
papers arguing that by overstating the true rate of the side effects the articles could influence high-risk patients to stop taking statins. He urged the
BMJ
to retract both papers. On May 15, 2014, the
BMJ
agreed to amend the statements about the side effects. It also said it would ask an independent commission to check whether the articles should be retracted.

Collins had another reason to be chagrined. Abramson had challenged the 2013 Cochrane Collaboration findings. All their
previous publications had urged caution in prescribing statins to people at low risk of heart disease and stroke, but then they changed their tune. They did so because of a study led by Collins and his colleague Anthony Keech at the University of Sydney.

‘It was this work that set the ball rolling', says Shah Ebrahim, an author of the Cochrane report. Published in the
Lancet
in May 2012, the report was based on the Cholesterol Treatment Trialists' collaboration (CTT). This study of 170 000 patients is the most comprehensive one could imagine on the effects of statins. Begun in 1990, shortly after the introduction of statins, it has collated data on most of the randomised controlled trials of statins in populations around the world for 24 years. Although funded by the drug companies that developed statins, the studies have been run by academic researchers who pool their results, cross-check each other's analysis and finally report using all the available data. ‘For the last 23 years we've met each November with representatives from each of the trials', explains Keech.

Studies such as the 1994 Scandinavian Simvastatin Survival Study 4S showed statins reduced deaths in people who had already had a heart attack or stroke or were otherwise at high risk. But over the years the studies tackled different questions: were statins useful for older people, for women, for people with existing diabetes, for people with high blood pressure?

But what about low-risk people such as Browning? Would they benefit from taking statins? CTT measured the rate of heart attacks, strokes, surgery to unblock arteries, and deaths in such people without evidence of disease. They were compared to a control group who did not take statins. They found that, for every unit of cholesterol lowered, people reduced their risk of a cardiovascular event by about 20 per cent.

‘The critical point was that, for the first time, an analysis of the effect of statins in people without disease but at high, moderate, low and very low risk was presented – it showed consistent
benefits across all these groups,' explained Ebrahim.

Overall, the risk of serious side effects was low. One in 10 000 reported a rare form of muscle breakdown known as rhabdomyolysis. There also appeared to be a 9 per cent increased risk for developing diabetes. But overall, the patients gained by avoiding cardiovascular events. That was reflected in the final figures – overall a slight reduction (9 per cent in the risk of death from all causes. And for every unit of cholesterol lowered, there were 11 fewer cardiovascular events per 1000 people. In an accompanying commentary in the
Lancet
in April 2012, Ebrahim, who serves as coordinating editor of the Cochrane Heart Group, and colleague Juan Pablo-Casas, paraphrased the findings of the CTT this way: ‘Men and women, old and young, and people with and without cardiovascular disease all benefit.'

Moreover, they suggested that medical guidelines should lower the threshold for taking statins to people whose risk was greater than 10 per cent over ten years – which includes 83 per cent of men over 50 and 56 per cent of women over 60. Indeed the title of their
Lancet
paper was ‘Statins for all by the age of 50?'

Abramson and colleagues were unconvinced. They reevaluated the CTT meta-analysis – but in a curious way. They ignored the findings on reductions of heart attacks, strokes or surgery to clear blocked arteries because they considered these endpoints were subject to bias. Instead they focused on deaths from any cause. Their conclusion: for people whose risk was lower than 10 per cent statins did not significantly reduce the risk of death.

Abramson's decision to focus only on deaths strikes some cardiologists as strange. ‘I refuse to believe that I should only do primary prevention to prevent total mortality,' commented Donald Lloyd-Jones at Northwestern University in Chicago, a member of the panel that developed the most recent US statin guidelines. ‘Patients are much more worried about having a
stroke or a major heart attack and living with that; they're not only focused on what's going to kill them.'

He adds the only reason Abramson didn't see a ‘statistically significant' effect in mortality is that in the lower risk group too few people died over the five-year course of these studies to observe a significant effect. Wait long enough, Lloyd-Jones says, and the ‘trend' will reach significance.

* * * * *

Nevertheless, Abramson and colleagues had many supporters. By late July 2014, close to 500 people, including many doctors and researchers, had signed an open letter on the website of the non-profit Lown Institute asking the
BMJ
not to retract the articles. This shows that ‘in the medical community (of) practitioners and researchers, a significant number of people are sceptical about the push to spread the use of statins to lower-risk patients,' says Vikas Saini, a cardiologist and president of the institute. ‘I certainly haven't seen enough proof to warrant changing guidelines and prescribing statins to another billion patients on the planet.' On 1 August, the
BMJ
panel decided against retracting the two papers. But that's hardly the end of the story.

What is one to make of it when medical titans do battle?

One reading is that the battlelines appear to be drawn between clinicians, who see individual patients, and epidemiologists, who see data on tens or hundreds of thousands of patients.

Clinicians believe their patients when they complain of muscle pains or memory loss after taking statins. When they go off the pills, they stop complaining. ‘I'm a simple man; that's good enough for me,' says GP David Bailey in the BBC TV program
Trust me, I'm a doctor.
Bailey refers to epidemiologists such as Rory Collins, who was also interviewed for the program, as being in an ‘ivory tower'.

But when patients are prescribed statins, some would doubtless read the packet information with its long list of possible side effects. What if they are imagining those ailments or falsely attributing new aches and pains and memory loss – all common in middle-age – to statins? It's known as the nocebo effect – ‘the evil twin of the placebo effect' as Ben Goldacre, the celebrity author of
Bad Science
, puts it. To see it in action he suggests: ‘When sitting on a sofa with friends, suddenly ask: “does this thing have fleas in it?”.'

Could many statin side effects be explained by nocebo?

‘I've stopped trying to work it all out, because the patients' beliefs are the most important factor,' admits David Sullivan, a physician and researcher at the University of Sydney. ‘I see a huge number of patients with these complaints, I don't know to what degree it is the power of suggestion, but it's a tragedy if they miss out on the benefits.'

In March 2015 two studies gave more weight to the power of suggestion. One was a meta-analysis published in the
European Journal of Preventive Cardiology.
Goldacre, who is also an epidemiologist at the London School of Tropical Medicine and Hygiene, was a co-author. He and colleagues trawled though 62 randomised controlled trials picking out 14 of the best primary prevention trials.

Their findings were stunning: ‘Cholesterol-lowering statins have almost no side effects,' blared the newspaper headlines.

Indeed, the paper found that with the exception of a slightly increased risk of diabetes, most common side effects attributed to statins were found in the placebo group at around the same rate. These included muscular weakness, muscle aches, back pain, newly diagnosed cancer, kidney problems, insomnia, gastrointestinal disturbance, nausea, indigestion, diarrhoea, constipation, fatigue, headache and a more than ten-fold increase of creatine kinase (a muscle enzyme whose levels rise after injury).