GPs and the public have been ‘misled’ by exaggerated claims about the harms of statins based on flimsy research, a team of leading international academics has claimed.
The team, led by Professor Rory Collins at the Oxford Clinical Trials Unit, have released a new review of statin data in The Lancet, which they said showed the drugs’ benefits have been underestimated, while the side effects have been overstated.
Professor Collins’ team said their new findings should help GPs and patients make ‘informed decisions’ about the pros and cons of statins.
But leading GP critics said the report would not allay their concerns that the drugs’ harms may outweigh their benefits as repeated calls for an independent study of all the evidence from statins trials, including adverse event data that have not been forthcoming.
Professor Collins had been in a row with the BMJ over two articles that claimed muscle side effects were much higher than reported in randomised trials, while the BMJ has been blamed for stoking negative reports resulting in patients stopping the drugs.
The latest review, co-authored by an array of international cardiology and epidemiology experts, claims the observational studies about the effects of statin therapy – including those cited by the BMJ papers – are unreliable, and re-analyses all the randomised trials evidence published to date.
The re-analysis showed that for every 10,000 people taking the equivalent of atorvastatin 40mg daily – lowering LDL cholesterol by about 2 mmol/L or 77 mg/dL – for five years:
- 500 taking it for primary prevention would be spared a first ever cardiovascular event such as a heart attack, stroke or coronary intervention;
- 1,000 with a history of vascular disease would be spared a further cardiovascular event;
- The number of events avoided would be even greater with longer treatment.
Importantly the team said the benefits were much greater than commonly taken from many earlier randomised trials, where the average reduction in cholesterol was 1mmol/L.
Meanwhile, these benefits would be at the cost of just five additional cases of myopathy and between 50 and 100 new cases of diabetes.
Professor Collins conceded the review did not include the full ‘hidden data’ on adverse events, but said his team are continuing to seek from trials investigators.
However, the study claims that the ‘large-scale evidence available from randomised trials also indicates that it is unlikely that large absolute excesses in other serious adverse events still await discovery’ and is ‘unlikely to materially alter the balance of benefits and harms’.
Professor Collins commented: ‘Our review shows that the numbers of people who avoid heart attacks and strokes by taking statin therapy are very much larger than the numbers who have side-effects with it.’
He added that, given the side effects were reversible, ‘there is a serious cost to public health from making misleading claims about high side-effect rates that inappropriately dissuade people from taking statin therapy despite the proven benefits’.
But Dr Martin Brunet, a GP trainer in Surrey and member of the RCGP overdiagnosis group, who has previously questioned the value of statins in primary prevention, said the new analysis would not reassure concerned GPs.
Dr Brunet said: ‘You can’t have a good debate about how much good and harm statins do if commercial companies are still holding back data.
‘What I would really like is for something like a Cochrane review from an independent group, someone who doesn’t have their career based on this and can see all the data – that review, I might change my practice on.’
Dr Kailash Chand, retired GP and former deputy chair of BMA council, who is an outspoken critic of expanding statin use, said: ‘If they want this paper to have any credibility they have to release the full data.’
Lancet 2016; available online 8 September
How the statin debacle unfolded
The controversy around statins in 2013 and 2014 coincided with widespread criticism of NICE’s decision to recommend millions more people take the drugs for primary prevention of cardiovascular disease, by lowering the 10-year risk threshold for primary prevention from 20% to 10%.
Leading UK doctors had urged NICE to backtrack on that decision warning it risked losing the confidence of the GP profession without better evidence to justify such widespread statin use, and the GPC called on NICE to pull back until full data on side effects from all industry trials were made publicly available for independent scrutiny.
Pulse revealed at the time that most GPs disagreed with NICE’s decision – a survey showed nearly six out of ten rejected it outright and a similar proportion said they would not take a statin themselves at that level of risk, nor recommend a family member do so.
Around the same time Professor Collins publicly called on the BMJ to retract two papers that claimed the true rate of side effects could be as high as 20%, based on incorrect interpretation of previous observational research. The BMJ refused to retract the articles but corrected the cited side effect evidence – actually that around 9% of people may have discontinued therapy because of a statin-related event – and convened an independent panel that subsequently ruled the journal had acted appropriately.
The NICE guidelines were published unchanged albeit with some nods to greater emphasis on shared decision making and prioritising lifestyle advice. However, a recent study – ironically published in the BMJ – found all the controversy had led to some 200,000 people stopping their statins – potentially leading to an additional 2,000 heart attacks or strokes over the next 10 years that would otherwise be avoided.