London School of Hygiene & Tropical Medicine

Doctors, patients and the public now have more help to make informed decisions about statin therapy, thanks to a major review of the available evidence on the safety and efficacy of the drug published in the Lancet.

The authors, including researchers from the London School of Hygiene & Tropical Medicine, warn that the benefits of statin therapy have been underestimated, and the harms exaggerated, because of a failure to acknowledge properly both the wealth of evidence from randomised trials and the limitations of other types of studies.

Research on statins has been ongoing for over 30 years, generating a large amount of data from a wide variety of patients. The review explains how the available evidence on the efficacy and safety of statin therapy should be interpreted.

It concludes that lowering cholesterol by 2 mmol/L with an effective low-cost statin therapy (e.g. atorvastatin 40 mg daily, which costs about £2 per month in the UK) for five years in 10,000 patients would: 

• Prevent major cardiovascular events (heart attacks, ischaemic strokes and coronary artery bypasses) in 1,000 people with pre-existing vascular disease ('secondary prevention'), and in 500 people who are at increased risk (eg, due to their age or having hypertension or diabetes) but have not yet had a vascular event ('primary prevention').

• Cause five cases of myopathy, a rare condition involving muscle pain, tenderness, or weakness accompanied by significant increases in blood creatine kinase concentrations, one of which might progress to the more severe condition of rhabdomyolysis if the statin is not stopped. It would also cause 5-10 haemorrhagic strokes, 50-100 new cases of diabetes and up to 50-100 cases of symptomatic adverse events such as muscle pain.

Professor Liam Smeeth, co-author from the London School of Hygiene & Tropical Medicine, said: "The best available scientific evidence tells us that statins are effective, safe drugs that have a crucial role in helping prevent cardiovascular disease: the leading cause of morbidity and mortality worldwide."

The authors note that although further research may identify small additional beneficial or adverse effects, this is unlikely to materially alter the balance of benefits and harms for patients because of the evidence generated so far.

Professor Rory Collins, review author from the Clinical Trial Service Unit, University of Oxford, said: "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. In addition, whereas most of the side-effects can be reversed with no residual effects by stopping the statin, the effects of a heart attack or stroke not being prevented are irreversible and can be devastating.

"Consequently 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."

The review discusses the strengths and limitations of different types of studies. Randomised controlled trials are a robust and well recognised way of determining the effect of treatments. Whereas observational studies based on databases can generate hypotheses about associations between the use of drugs and health outcomes, randomised trials can determine cause and effect.

Earlier this year, the School announced the start of a new trial investigating the link between statins and muscle pains reported by people taking the drug.

Publication:

• Rory Collins, Christina Reith, Jonathan Emberson, Jane Armitage, Colin Baigent, Lisa Blackwell, Roger Blumenthal, John Danesh, George Davey Smith, David DeMets, Stephen Evans, Malcolm Law, Stephen MacMahon, Seth Martin, Bruce Neal, Neil Poulter, David Preiss, Paul Ridker, Ian Roberts, Anthony Rodgers, Peter Sandercock, Kenneth Schulz, Peter Sever, John Simes, Liam Smeeth, Nicholas Wald, Salim Yusuf, Richard Peto. Interpretation of the evidence for the efficacy and safety of statin therapy. The Lancet: DOI 10.1016/S0140-6736(16)31357-5

Related links:

• Side effects of statins investigated in new £1m trial

Related courses:

• Epidemiological Evaluation of Vaccines: Efficacy, Safety and Policy
• Practical Pharmacoepidemiology
• Pharmacoepidemiology & Pharmacovigilance (London-based)
• Pharmacoepideimiology & Pharmacovigilance by Distance Learning