by Jerome Burne
Last week an email containing what looked like a great story arrived in my inbox – drug kills 800,000 in Europe in 5 years! A quick check revealed that that this was no wild or dodgy claim. It was based on research by a cardiologist at Imperial College Professor Darryl Francis, just published in the European Heart Journal.
What’s more it had been covered in a blog on the site of top business magazine Forbes; the icing on the scandal cake was that within an hour of Francis’ paper going up on the website of the journal that published the paper, it had been removed on the grounds that due to an oversight it hasn’t been peer-reviewed. A cover-up getting underway?
So here, it seemed, were all the hallmarks of a big new drug scandal. And the more I dug into it, the more solid it became. The drug involve was a beta-blocker – a type of drug prescribed in large numbers to heart patients and people suffering from anxiety because it slows the heart rate and lowers blood pressure.
Drug making things worse
Used in this way they are generally considered safe, but when used during an operation to cut the risk of subsequent heart problems – a well-known side effect of surgery – evidence dating back years strongly suggested they make things worse. In fact according to the Imperial College research, this use kills 10,000 people a year in the UK alone.
The key evidence that they were dangerous came from a controlled trial involving 10,000 patients, published five years ago in the Lancet by Canadian researcher Professor Philip Devereaux. In an interview he told me that although the drugs did cut the number of heart attacks, they pushed up the death rate by considerably more and so shouldn’t be used for prevention in surgery.
However guidelines saying that, taking other evidence into account, they should be used for precisely that purpose from the prestigious European College of Cardiology (ECS) were still an official recommendation.
And as if this wasn’t enough to constitute an ongoing scandal, the final part of the story, as set out in Professor Francis’ paper, was that the research supporting the use of beta-blockers in surgery was discovered, in 2011, to be either partially missing or obviously fraudulent.
Conflict of interests?
This was deeply embarrassing for the ESC because the favourable research had been done by Dr Don Poldermans of the Erasmus Medical Center in Rotterdam, who was the Chairman of the ESC’s Committee that had drawn up the guidelines.
Under Poldermans’ leadership the committee had decided that his research – finding the drug cut the death rate – cancelled out Devereaux’s paper finding that it increased it, leaving an agreement by both papers that beta-blockers reduced non-fatal heart attacks and so they were worth taking.
So the big scandal was – once the only bit of research showing that beta-blockers were worth it had been totally discredited nearly four years ago – why were the ESC guidelines still advising medical teams to use the drugs during surgery? It looked as if as many as 50,000 people in the UK alone could have died in the intervening period as a result of these highly misleading guidelines remaining unchanged.
But after getting all my ducks lined up in this way, the following day I decided not to write the story. Not because any of the facts I have set out were found to be wrong but because I couldn’t prove that the drugs were being used in this way in the UK. What I was left with was a story that showed just how unreliable supposedly evidence based medicine could be.
When doctors are personally liable
There was one more thing I discovered that, at first, seemed to make the story even stronger. It turned out that using beta-blockers to cut heart attack risk during surgery is not a licenced use in the UK. What this means is that the doctor who does this has to have reasonable evidence it could help and is personally responsible if something goes wrong.
(Drugs are licenced to treat particular conditions – pain, seizures– and if doctors use them to treat a different condition – a seizure drug to treat pain – they are then using the drug “off-label”. It is done quite often and there is a good clinical case for it but it means that the drug watchdog – the MHRA doesn’t collect any data on reported side-effects, so if there’s a problem, it’s very hard to detect it.)
So if beta-blockers were being regularly used in this way based on the unchanged ECS guidelines that could mean that large numbers of doctors could be personally liable for those 10,000 extra deaths a year. This was a prize-winning investigation!
But that only mattered if doctors in the UK were actually using the drugs in this way and I couldn’t prove they were. Several top cardiologists told me that while American and Europeans clinicians do it, UK doctors, having looked at the evidence, had decided not to.
Decision that could kill patients
They could of course be lying or simply wrong but because use of the drugs would be “off-label it wouldn’t be centrally recorded. That left no realistic way to check the extent of use, which killed it as a UK newspaper story. Who cares if a drug could be dangerous if no one is actually using it?
What was left was a big question mark over the way that evidence based medicine actually works. What about the role of bodies drawing up guidelines? Are there millions of people still getting treatment with a drug that raises their risk of heart problems because no one has changed the guidelines for years? Whose responsibility is it to alter guidelines when evidence changes? Surely not a UK clinician analysing the latest evidence?
In response to my queries the ESC claimed it had acted as fast as it could. But then during the two years between Polderman’s dismissal and publication of Francis’ paper last year, what was the evidence-based course of action? To give beta blockers and so saving lives according to guidelines or not to?
From what the UK physicians told me they look like the good guys. But it’s not that simple. They said they had decided not to use beta-blockers about ten years ago. But how could they have done that? Back in 2003 Polderman’s work looked like a strong reason to give the drugs. From evidence based perspective the UK physicians’ decision was going to kill patients by withholding the drug.