Health information around statins should be revised as most side effects listed in the product labels are not caused by the drugs, a major new study finds.
Published in The Lancet, the study analysed data from 23 large randomised double-blind trials using statins and involved more than 120,000 participants. Each trial was more than two years long, with 19 being placebo controlled and the remaining four comparing different statin doses.
The researchers found that only four of the 66 listed adverse outcomes were attributable to statins and only in a very small proportion of patients. These were: liver test changes, minor liver abnormalities, urinary changes and oedema.
Limited causal associations
Abnormal liver transaminases occurred in 783 of 62,028 participants allocated to statin therapy, corresponding to an annual incidence of 0.30%, compared with 556 of 61,912 participants allocated to placebo, with an annual incidence of 0.22% (rate ratio [RR] 1.41; 95% CI 1.26–1.57; P<0.0001) and an absolute annual excess risk of 0.09%.
Other liver function test abnormalities were reported in 651 statin-allocated participants (0.25% per annum) and 518 placebo-allocated participants (0.20% per annum), yielding an RR of 1.26 (95% CI 1.12–1.41; P=0.00010) and an absolute annual excess risk of 0.05%. When combined, the absolute annual excess risk for liver function test abnormalities was 0.13%.
Alteration in urinary composition was observed in 556 participants allocated to statins (0.21% per annum) compared with 472 allocated to placebo (0.18% per annum), corresponding to an RR of 1.18 (95% CI 1.04–1.33; P=0.0089) and an absolute annual excess risk of 0.03%.
Oedema occurred in 3,495 statin-allocated participants (1.38% per annum) and 3,299 placebo-allocated participants (1.31% per annum), yielding an RR of 1.07 (95% CI 1.02–1.12; P=0.0071) and an absolute annual excess risk of 0.07%.
No statistically significant excess risk was observed for clinically relevant liver disease outcomes, including hepatitis, hepatic failure or damage, cholestasis, jaundice, or hepatic steatosis.
Similarly, no causal association was identified for the remaining 62 prespecified adverse outcomes, including cognitive or memory impairment, dementia, depression, sleep disturbance, peripheral neuropathy, erectile or sexual dysfunction, interstitial lung disease, acute kidney injury, and pancreatitis.
Calls for updated statins health information
The researchers concluded that product labelling and other official sources of health information for these cholesterol-lowering drugs should be revised so that patients and their healthcare providers can make appropriately informed decisions regarding statin therapy.
Lead author Dr Christina Reith, associate professor at the University of Oxford’s Nuffield Department of Population Health, said: ‘Statins are life-saving drugs used by hundreds of millions of people over the past 30 years. However, concerns about the safety of statins have deterred many people who are at risk of severe disability or death from a heart attack or stroke.
‘Our study provides reassurance that, for most people, the risk of side effects is greatly outweighed by the benefits of statins.’
Professor Sir Rory Collins, emeritus professor of medicine and epidemiology at Oxford Population Health and senior author of the paper, added: ‘Statin product labels list certain adverse health outcomes as potential treatment-related effects based mainly on information from non-randomised studies which may be subject to bias.
‘We brought together all of the information from large, randomised trials to assess the evidence reliably. Now that we know that statins do not cause the majority of side effects listed in package leaflets, statin information requires rapid revision to help patients and doctors make better-informed health decisions.’
Previous work by the same researchers found that statin therapy caused muscle symptoms in only 1% of people during the first year of treatment.
