Summary
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
efficacy and safety of statin therapy. In addition, it discusses how
claims that statins commonly cause adverse effects reflect a failure to
recognise the limitations of other sources of evidence about the effects
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 first) that it continues to be taken. The absolute
benefits 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 effective 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 benefit) with pre-existing occlusive vascular
disease (secondary prevention) and in 500 patients (ie, 5% absolute
benefit) 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 benefits would accrue with more prolonged therapy, and these
benefits persist long term. The only serious adverse events that have
been shown to be caused by long-term statin therapy—ie, adverse effects
of the statin—are myopathy (defined 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 effective
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-effects on major vascular events has already been
taken into account in the estimates of the absolute benefits. 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 definitively 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 findings
that emerge about the effects of statin therapy would not be expected
to alter materially the balance of benefits and harms. It is, therefore,
of concern that exaggerated claims about side-effect 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.
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