Quantifying effect of statins on low density lipoprotein cholesterol,
ischaemic heart disease,and stroke: systematic review and meta-analysis |
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Authors: | M R Law N J Wald A R Rudnicka |
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Institution: | 1 Department of Environmental and Preventive Medicine, Wolfson Institute of Preventive Medicine, Barts and the London, Queen Mary''s School of Medicine and Dentistry, University of London, London EC1M 6BQ |
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Abstract: | Objectives To determine by how much statins reduce serum
concentrations of low density lipoprotein (LDL) cholesterol and incidence of
ischaemic heart disease (IHD) events and stroke, according to drug, dose, and
duration of treatment.Design Three meta-analyses: 164 short term randomised placebo
controlled trials of six statins and LDL cholesterol reduction; 58 randomised
trials of cholesterol lowering by any means and IHD events; and nine cohort
studies and the same 58 trials on stoke.Main outcome measures Reductions in LDL cholesterol according to
statin and dose; reduction in IHD events and stroke for a specified reduction
in LDL cholesterol.Results Reductions in LDL cholesterol (in the 164 trials) were 2.8
mmol/l (60%) with rosuvastatin 80 mg/day, 2.6 mmol/l (55%) with atorvastatin
80 mg/day, 1.8 mmol/l (40%) with atorvastatin 10 mg/day, lovastatin 40 mg/day,
simvastatin 40 mg/day, or rosuvastatin 5 mg/day, all from pretreatment
concentrations of 4.8 mmol/l. Pravastatin and fluvastatin achieved smaller
reductions. In the 58 trials, for an LDL cholesterol reduction of 1.0 mmol/l
the risk of IHD events was reduced by 11% in the first year of treatment, 24%
in the second year, 33% in years three to five, and by 36% thereafter (P <
0.001 for trend). IHD events were reduced by 20%, 31%, and 51% in trials
grouped by LDL cholesterol reduction (means 0.5 mmol/l, 1.0 mmol/l, and 1.6
mmol/l) after results from first two years of treatment were excluded (P <
0.001 for trend). After several years a reduction of 1.8 mmol/l would reduce
IHD events by an estimated 61%. Results from the same 58 trials, corroborated
by results from the nine cohort studies, show that lowering LDL cholesterol
decreases all stroke by 10% for a 1 mmol/l reduction and 17% for a 1.8 mmol/l
reduction. Estimates allow for the fact that trials tended to recruit people
with vascular disease, among whom the effect of LDL cholesterol reduction on
stroke is greater because of their higher risk of thromboembolic stroke
(rather than haemorrhagic stroke) compared with people in the general
population.Conclusions Statins can lower LDL cholesterol concentration by an
average of 1.8 mmol/l which reduces the risk of IHD events by about 60% and
stroke by 17%. |
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