Interpretation of the evidence for the efficacy and safety of statin therapy
Creators: name: Schulz, Kenneth
name: Martin, Seth
name: Neal, Bruce
name: Rodgers, Anthony
name: Danesh, John
name: Ridker, Paul
name: Simes, John
name: Yusuf, Salim
name: Poulter, Neil
name: Peto, Richard
name: Wald, Nicholas
name: Sever, Peter
name: Reith, Christina
name: Smith, George Davey
name: Collins, Rory
name: MacMahon, Stephen
name: Emberson, Jonathan
name: Evans, Stephen
name: Armitage, Jane
name: Smeeth, Liam
name: Law, Malcolm
name: Baigent, Colin
name: Blumenthal, Roger
name: Preiss, David
name: Sandercock, Peter
name: DeMets, David
name: Roberts, Ian
name: Blackwell, Lisa
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2016

description: This Review is intended to help clinicians, patients, and the public make informed decisions about statin therapy for
the prevention of heart attacks and strokes. It explains how the evidence that is available from randomised controlled
trials yields reliable information about both the effi cacy and safety of statin therapy. In addition, it discusses how
claims that statins commonly cause adverse eff ects refl ect a failure to recognise the limitations of other sources of
evidence about the eff ects of treatment. Large-scale evidence from randomised trials shows that statin therapy reduces
the risk of major vascular events (ie, coronary deaths or myocardial infarctions, strokes, and coronary revascularisation
procedures) by about one-quarter for each mmol/L reduction in LDL cholesterol during each year (after the fi rst) that
it continues to be taken. The absolute benefi ts of statin therapy depend on an individual’s absolute risk of occlusive
vascular events and the absolute reduction in LDL cholesterol that is achieved. For example, lowering LDL cholesterol
by 2 mmol/L (77 mg/dL) with an eff ective low-cost statin regimen (eg, atorvastatin 40 mg daily, costing about £2 per
month) for 5 years in 10 000 patients would typically prevent major vascular events from occurring in about
1000 patients (ie, 10% absolute benefi t) with pre-existing occlusive vascular disease (secondary prevention) and in
500 patients (ie, 5% absolute benefi t) who are at increased risk but have not yet had a vascular event (primary
prevention). Statin therapy has been shown to reduce vascular disease risk during each year it continues to be taken,
so larger absolute benefi ts would accrue with more prolonged therapy, and these benefi ts persist long term. The only
serious adverse events that have been shown to be caused by long-term statin therapy—ie, adverse eff ects of the
statin—are myopathy (defi ned as muscle pain or weakness combined with large increases in blood concentrations
of creatine kinase), new-onset diabetes mellitus, and, probably, haemorrhagic stroke. Typically, treatment
of 10 000 patients for 5 years with an eff ective regimen (eg, atorvastatin 40 mg daily) would cause about 5 cases of
myopathy (one of which might progress, if the statin therapy is not stopped, to the more severe condition of
rhabdomyolysis), 50–100 new cases of diabetes, and 5–10 haemorrhagic strokes. However, any adverse impact
of these side-eff ects on major vascular events has already been taken into account in the estimates of the absolute
benefi ts. Statin therapy may cause symptomatic adverse events (eg, muscle pain or weakness) in up to about
50–100 patients (ie, 0·5–1·0% absolute harm) per 10 000 treated for 5 years. However, placebo-controlled randomised
trials have shown defi nitively that almost all of the symptomatic adverse events that are attributed to statin therapy in
routine practice are not actually caused by it (ie, they represent misattribution). The large-scale evidence available
from randomised trials also indicates that it is unlikely that large absolute excesses in other serious adverse events
still await discovery. Consequently, any further fi ndings that emerge about the eff ects of statin therapy would not be
expected to alter materially the balance of benefi ts and harms. It is, therefore, of concern that exaggerated claims
about side-eff ect rates with statin therapy may be responsible for its under-use among individuals at increased risk of
cardiovascular events. For, whereas the rare cases of myopathy and any muscle-related symptoms that are attributed
to statin therapy generally resolve rapidly when treatment is stopped, the heart attacks or strokes that may occur if
statin therapy is stopped unnecessarily can be devastating.