Statin safety and efficacy: eminence or evidence-based medicine?

With interest I have observed the recent issues over the safety of statin therapy unfold in the BMJ. I was somewhat staggered to see the BBC headlines, on the 15th May, which reported two articles in the BMJ on statins were to be investigated and could be retracted.

One of these papers was an opinion piece about saturated fats, which reported 20% of participants on statins had side effects resulting in discontinuation of the drug.

‘A recent “real world” study of 150 000 patients who were taking statins showed “unacceptable” side effects—including myalgia, gastrointestinal upset, sleep and memory disturbance, and erectile dysfunction—in 20% of participants, resulting in discontinuation of the drug’

Whereas the actual study referred to, authored by Zhang, actually reported 17.4% of patients had a statin related event documented, of whom 59.2% discontinued the statin at least temporarily.  So, by my calculations, 1 in 10 (10.3%) discontinued the drug temporarily.

And most patients who were re-challenged (92.2%) were still taking a statin 12 months after the statin-related event.

The article, by Malhotra, is just the sort of piece I would normally bypass. How an opinion on saturated fats ends up headlining adverse events of statins is beyond me.

The second of these papers, the Abramson paper, is an analysis on whether people at low risk of cardiovascular disease should take a statin. In this paper, Abramson referred to the same study, stating side effects of statins occurred in about 18% of people.

‘A retrospective cohort study found that 18% of statin treated patients had discontinued therapy (at least temporarily) because of statin related adverse events. Forty per cent of the adverse events were related to musculoskeletal symptoms.’

Both article, therefore report the actual figure sloppily, yet this is hardly retraction territory, more get the corrections in fast.

Whilst the Abramson article makes an objective analysis of the meta-analysis data provided by the cholesterol treatment trialist collaboration, it seems, irrespective of whether quoting the Zhang paper’s figure was wrong or not, the issue with the analysis was its inappropriate use of just one or two observational study to inform adverse events – what is needed – and should be mandatory – in such an article is a systematic review of observational studies.

However, observational studies can only tell you so much – they inform you of the adverse event data associated with people who also take statins – they do not inform you of the adverse event rates of statins.  RCTs are still the gold standard  for assessing both benefits and harms – don’t forget this!

In terms of the  BMJ panel – for which the BBC now reports the BMJ was ‘right’ with regard to the statins claims row – one point was that the ‘individual patient level data for the relevant trials are held in confidence by the investigators and have not yet been made available for public scrutiny.

The issue with IPD data is often the investigators doing the IPD don’t have the right to release the data; it is often the original trialist who has to make it available.

In terms of making the data available it is clearly important, particularly  when you read a recent editorial by Editorial in the Annals of Internal Medicine, which reports that two meta analyses of statins in primary prevention differed in their statistical conclusions by less than half a percent; yet whilst one review states:

“This literature-based meta-analysis did not find evidence for the benefit of statin therapy on all-cause mortality in a high-risk primary prevention set-up.”

The other review states:

“Reductions in all-cause mortality, major vascular events and revascularisations were found with no excess of adverse events among people without evidence of CVD treated with statins”.

Feel confused?

The current problem relates to evidence largely focusing on benefits, taken alongside adverse event in trials tending to be lower than those observed in observational studies, which can be accentuated by some trials having run in periods that underestimate adverse effects, has meant there is still uncertainty in the reporting of overall harms. Particularly given recent publications highlighting the under reporting of adverse events,

The Therapeutics Letter – Statins: proven and associated harms, provides a good overview of the harm evidence

You can tell there are problems with the evidence-base as uncertainty continues to drive both sides of the argument. What is clearly needed is more evidence not more eminence.