A major review of the available evidence on the safety and efficacy of statin therapy, published in The Lancet, intends to help doctors, patients and the public make informed decisions about the use of the drugs.
The authors 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 randomized studies 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 published explains how the available evidence on the efficacy and safety of statin therapy should be interpreted, and concludes that:
Lowering cholesterol by 2 mmol/L with an effective low-cost statin therapy for 5 years in 10,000 patients would:
Prevent major cardiovascular events (heart attacks, ischemic strokes and coronary artery bypasses) in 1000 people with pre-existing vascular disease, and in 500 people who are at increased risk but have not yet had a vascular event.
Cause 5 cases of myopathy (one of which might progress to the more severe condition of rhabdomyolysis, if the statin is not stopped), 5-10 hemorrhagic strokes, 50-100 new cases of diabetes and up to 50-100 cases of symptomatic adverse events (such as muscle pain).
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.
“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,” says review author Professor Rory Collins from University of Oxford.
Benefits of statin therapy
Evidence from large population studies, combined with studies in animals, genetic research and randomized controlled trials have confirmed a causal link between higher levels of LDL cholesterol in the blood and higher risks of vascular disease.
Meta-analyses of large randomized controlled trials of statin therapy indicate that each 1 mmol/L reduction in LDL cholesterol with statin therapy reduces the risk of coronary deaths and heart attacks, ischemic strokes (strokes due to blood clots) and coronary revascularization procedures by about 25% during each year (after the first) that treatment continues to be taken.
The meta-analyses also indicate that larger reductions in LDL cholesterol with statin therapy produce larger reductions in the risks of these major vascular events.
Harms of statin therapy
Myopathy is a rare condition involving muscle pain, tenderness, or weakness accompanied by significant increases in blood creatine kinase concentrations. Evidence from observational studies and randomized trials points to a causal effect of statin therapy on myopathy.
However, the risk of myopathy is low: about 1 extra case per 10,000 patients taking an effective statin regimen (such as atorvastatin 40 mg daily) during each year of treatment.
In addition, evidence from randomized trials has identified an increased risk of diabetes due to statin therapy: about 10-20 extra cases of diabetes developing per 10,000 treated patients per year.
This excess of diabetes occurs mainly in people who are already at increased risk of developing diabetes, and its clinical significance is uncertain.
In particular, although diabetes is associated with increased risk of vascular disease, statin therapy produces substantial reductions in vascular disease.
Some observational studies have suggested statin therapy may be associated with an increased risk of hemorrhagic stroke. And randomized trials indicate that statin therapy may increase the risk of hemorrhagic stroke by about one-fifth.
Typically, in Western populations, this would correspond to an increase of about 5-10 extra cases per 10,000 treated patients per year.
In most circumstances, the reductions in ischemic strokes produced by statin therapy are much bigger than the increases in hemorrhagic strokes, so the risk of stroke of any kind is reduced substantially.
Writing in a linked Comment, Dr Richard Horton, editor-in-chief of The Lancet says: “Controversy over the safety and efficacy of statins has harmed the health of potentially thousands of people in the UK…”
“That is why we are publishing a comprehensive scientific review about the efficacy and safety of statin therapy by researchers who have made substantial contributions to the science of statins.”
“The purpose of this review is to help doctors and patients make informed decisions about the use of this important drug class.”