Quantifying effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis

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%.

Atorvastatin in Factorial with Omega-3 EE90 Risk Reduction in Diabetes (AFORRD): a randomised controlled trial

“…A meta-analysis of 164 short-term statin trials reported a 43% reduction in LDL-C with atorvastatin 20 mg/day, compared with the 44% reduction we observed [29]. The 21% reduction in triacylglycerol concentration was similar to the 19% reduction reported with atorvastatin 10 mg/day by CARDS in patients with type 2 diabetes [7].…”

Interpretation of the evidence for the efficacy and safety of statin therapy

“…Moreover, the absolute reduction in vascular risk per mmol/L reduction in LDL cholesterol would also be expected to be similar for individuals who are at comparable levels of risk but present with different cholesterol concentrations. The results of randomized controlled trials of statin therapy support these epidemiological expectations (see below), [31][32][33]156,157 and treatment guidelines now tend to focus on an individual's risk of having atherosclerosis-related events as well as on their LDL cholesterol level. 158,159 Lower concentrations of cholesterol have been associated in observational studies with higher rates of all-cause mortality, particularly in older people.…”

Vulnerabilities to Health Disparities and Statin Use in the REGARDS (Reasons for Geographic and Racial Differences in Stroke) Study

“…Statin use has been well documented to reduce incidence of major coronary and cerebrovascular events in cardiovascular disease 1, 2. The Adult Treatment Panel III (ATP III) guidelines recommended statin use for persons with elevated low‐density lipoprotein cholesterol (LDL‐C) in 2002 3.…”