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Quantifying effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic
M R Law1, N J Wald, A R Rudnicka
1Department 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. m.r.law@qmul.ac.uk
Insights
Statins significantly lower low-density lipoprotein (LDL) cholesterol, reducing the risk of ischaemic heart disease (IHD) events by approximately 60% and stroke by 17%. These benefits are dose-dependent and increase with treatment duration.
Area of Science:
- Cardiovascular Medicine
- Pharmacology
- Epidemiology
Background:
- High serum low-density lipoprotein (LDL) cholesterol is a major risk factor for cardiovascular events.
- Statins are widely prescribed to manage hypercholesterolemia and prevent cardiovascular disease.
Purpose of the Study:
- To quantify the reduction in LDL cholesterol achieved by statins.
- To determine the impact of statin therapy on the incidence of ischaemic heart disease (IHD) events and stroke.
- To analyze these effects based on drug, dosage, and treatment duration.
Main Methods:
- Meta-analysis of 164 randomized placebo-controlled trials assessing LDL cholesterol reduction with six statins.
- Meta-analysis of 58 randomized trials on cholesterol-lowering interventions and IHD events.
- Analysis of nine cohort studies and the same 58 trials to evaluate stroke incidence.
Main Results:
- High-dose statins (e.g., rosuvastatin 80 mg, atorvastatin 80 mg) achieved LDL cholesterol reductions of up to 60%.
- A 1.0 mmol/l reduction in LDL cholesterol was associated with a progressive decrease in IHD event risk over time, reaching 36% after several years.
- An average LDL cholesterol reduction of 1.8 mmol/l was estimated to reduce IHD events by 61% and stroke by 17%.
Conclusions:
- Statins effectively lower LDL cholesterol concentrations.
- Achieving an average LDL cholesterol reduction of 1.8 mmol/l with statins significantly reduces the risk of IHD events and stroke.
- The magnitude of benefit is related to the degree of LDL cholesterol lowering and treatment duration.
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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