Comprehensive analysis finds statins do not cause 62 side effects which have been commonly attributed to them.
A landmark review has found that statins are unlikely to cause most of the side effects listed on medicine labels, prompting experts to urge updates to patient information leaflets.
Researchers at Oxford Population Health performed the most comprehensive review of statin side effects to date, using data from large-scale randomised studies, including 123,940 participants in 19 trials comparing statin to placebo and 30,724 participants comparing intensity of statin therapy across four trials.
Results have been published in The Lancet.
The number of reports for side effects were similar between statins and placebo for almost all side effects listed in the medication information leaflets, such as memory loss or dementia, depression, sleep disturbance, erectile and sexual dysfunction, weight gain, nausea, fatigue or headache.
“These symptoms are happening all the time,” said Professor Anthony Keech, cardiologist at Royal Prince Alfred Hospital, director of Cardiovascular Research at the NHMRC clinical trials centre at the University of Sydney, and one of the research paper’s authors.
“In fact, 25% of patients during these trials over about five years reported muscle pains at some time or other during the course of their follow up.
“The issue, though, was that 25% of the placebo group also reported muscle pains during the course of their follow up, and the difference was only about one in 100 in excess for the statin treated patients versus patients taking a matching placebo.
“So, it’s not that these symptoms aren’t occurring in our patients all the time; it’s just that they’re mostly not due to the statins at all.”
“This means that we now have really good evidence that although these things may well happen when people are taking statins, that statins are not the cause of these problems,” lead study author Associate Professor Christina Reith from the Oxford Population Health at the University of Oxford said in a news briefing yesterday.
“These drugs save lives, they prevent strokes, they prevent heart attacks, have all sorts of benefits, and it really comes at very little cost, either in the cost of the medication or the cost as far as side effects are concerned,” said Professor Gary Jennings, chief medical advisor of the Heart Foundation.
The analysis concluded that statin use was not associated with a greater risk of 62 of 66 prespecified outcomes, showing no false discovery rate (FDR)-significant increase compared with placebo.
Of the four exceptions, the most notable was abnormal liver transaminases, which occurred more frequently with statins than placebo (RR 1.41, 95% CI 1.26–1.57).
“We did see a small increase about 0.1% for abnormal liver blood tests,” Professor Reith said.
“However, what we also saw was that this did not seem to be accompanied by an increase in serious liver disease such as hepatitis or liver failure.”
The increased risk also appeared to be dose-related; more intensive therapy was associated with a higher risk of abnormal liver transaminases compared with less intensive therapy (RR 2.06, 95% CI 1.66–2.57).
This was mainly driven by atorvastatin 80mg/day, while rosuvastatin 20mg did not show a similarly strong signal. When high-dose atorvastatin trials were excluded, the magnitude of the association was reduced (RR 1.30, 95% CI 1·16–1·46).
Another exception were other liver function test abnormalities, including alkaline phosphatase, abnormal gamma-glutamyl transferase, and non-specific LFT abnormalities (RR 1.26, 95% CI 1.12–1.41, absolute annual excess 0.05%).
Urinary composition alteration was another exception (RR 1.18, 95% CI 1.04–1.33). Post-hoc analyses showed that this excess was driven by proteinuria-related abnormalities (RR 1.20, 95% CI 1.02–1.42; absolute annual excess 0.02%), with no effect on haematuria or leukocyturia and no FDR-significant excess with more intensive therapy. There were also no increased risks for major renal outcomes.
Finally, statin therapy was associated with a small increase in risk of oedema (RR 1.07, 95% CI 1.02–1.12, absolute annual excess 0.07%).
“We can say now that statins are not the cause of the vast majority of medical issues listed as potential side effects in statin and patient information leaflets. This means that the benefits of statins in reducing major events like heart attacks and strokes significantly outweigh their risks,” said Professor Reith.
Related
“We hope that this prompts calls for revision of statin drug labels and related health information available through other sources to enable doctors and patients to make informed decisions in the future.”
When asked about revising the medication leaflets at yesterday’s briefing, Professor Jennings explained that it was much easier to add things than have them removed.
“It is quite difficult to have things taken off the list. There’s no definite process for that,” he said.
“I don’t kind of imagine there’s anything stronger than this with a commonly used drug for a major condition, which definitely saves lives, where we could re-examine that process.”
He also raised the point that it may be in the best interest of the pharmaceutical companies to have a long list of possible side effects so that they’re covered legally.
Professor Reith explained that since statins were off patent and produced by a range of companies, there wasn’t as clear a way forward as there would be for a new drug on the market.
“We’re in discussion with regulators, and we’re hoping they take a keen interest in these results, and obviously national health bodies as to what should be done about this,” she said.
“We hope it prompts a discussion as to how best to change this, these labels and this information, because I think one big problem is that it’s not well understood by certainly most patients and people, but also, actually by many doctors.”
The study could not speak to the side effects associated with ceasing statins, which have typically also been a concern amongst users and prescribers.
“It’s something we have tried hard to look at but has proven challenging. We do list that as a limitation in our paper, but I think that still doesn’t detract from our main findings,” said Professor Reith.
“This was the 38 million records and over 840 data sets, which is why it’s taken us a bit of time to do this.”
“Over two million people in Australia are taking statins, and they’re in a group where the demographic tends to shift towards older people, but they’re getting a lot of these other, you know, aches and pains and everyday symptoms,” said Professor Jennings.
“And I think we quite rightly have a natural suspicion of drugs that need to be taken for life when we know there are potentially lifestyle alternatives.
“But this is a case where, if the drugs are indicated, they are clearly more beneficial than anything else that you can do, notwithstanding they need to be done in combination with good nutrition, physical activity, not smoking, all of those other things.”
