Meta-analysis · Lancet 2012
CTT 2012 low risk
The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials.
The bottom line
Even in people at low baseline cardiovascular risk, lowering LDL cholesterol with statin therapy reduces major vascular events and all-cause mortality without increasing cancer risk, suggesting current risk-threshold guidelines for statin use may need reconsideration.
BenefitUS status: Not applicable
At a glance
- Medicine
- Statin therapy (lowering LDL cholesterol)
- Compared with
- Statin vs control (22 trials); more statin vs less statin (5 trials)
- People
- 174,149
- Who took part
- Participants from 27 randomised statin trials, stratified into five categories of baseline 5-year major vascular event risk on control therapy (<5%, ≥5% to <10%, ≥10% to <20%, ≥20% to <30%, ≥30%)
- Design
- Meta-analysis of individual participant data from 27 randomised trials
- Follow-up
- 4·8 years (statin vs control trials, median); 5·1 years (more vs less statin trials)
- Main question
- Major vascular events (major coronary events [non-fatal myocardial infarction or coronary death], strokes, or coronary revascularisations) per 1·0 mmol/L LDL cholesterol reduction
Main result
RR 0·79, 95% CI 0·77-0·81, per 1·0 mmol/L LDL cholesterol reduction; proportional reduction at least as big in the two lowest risk categories as higher risk categories (RR from lowest to highest risk: 0·62 [99% CI 0·47-0·81], 0·69 [99% CI 0·60-0·79], 0·79 [99% CI 0·74-0·85], 0·81 [99% CI 0·77-0·86], and 0·79 [99% CI 0·74-0·84]; trend p=0·04)
Effect on LDL cholesterol
Mean LDL cholesterol difference 1·08 mmol/L (statin vs control trials); 0·51 mmol/L (more vs less statin trials)
Other results
In participants without a history of vascular disease, statins reduced the risks of vascular (RR per 1·0 mmol/L LDL cholesterol reduction 0·85, 95% CI 0·77-0·95) and all-cause mortality (RR 0·91, 95% CI 0·85-0·97), and the proportional reductions were similar by baseline risk.
Safety
There was no evidence that reduction of LDL cholesterol with a statin increased cancer incidence (RR per 1·0 mmol/L LDL cholesterol reduction 1·00, 95% CI 0·96-1·04), cancer mortality (RR 0·99, 95% CI 0·93-1·06), or other non-vascular mortality.
In the trial's own words
“Reduction of LDL cholesterol with a statin reduced the risk of major vascular events (RR 0·79, 95% CI 0·77-0·81, per 1·0 mmol/L reduction), largely irrespective of age, sex, baseline LDL cholesterol or previous vascular disease, and of vascular and all-cause mortality.”
Quoted from the abstract of Lancet 2012, checked word for word against PubMed. PubMed 22607822 · Full paper (DOI)
Common questions
What did the CTT 2012 low risk trial find?
Even in people at low baseline cardiovascular risk, lowering LDL cholesterol with statin therapy reduces major vascular events and all-cause mortality without increasing cancer risk, suggesting current risk-threshold guidelines for statin use may need reconsideration.
Who was in CTT 2012 low risk?
174,149 people. Participants from 27 randomised statin trials, stratified into five categories of baseline 5-year major vascular event risk on control therapy (<5%, ≥5% to <10%, ≥10% to <20%, ≥20% to <30%, ≥30%).
What was CTT 2012 low risk's main result?
RR 0·79, 95% CI 0·77-0·81, per 1·0 mmol/L LDL cholesterol reduction; proportional reduction at least as big in the two lowest risk categories as higher risk categories (RR from lowest to highest risk: 0·62 [99% CI 0·47-0·81], 0·69 [99% CI 0·60-0·79], 0·79 [99% CI 0·74-0·85], 0·81 [99% CI 0·77-0·86], and 0·79 [99% CI 0·74-0·84]; trend p=0·04)
How much did LDL cholesterol change in CTT 2012 low risk?
Mean LDL cholesterol difference 1·08 mmol/L (statin vs control trials); 0·51 mmol/L (more vs less statin trials)
Related trials
- CTT 2010 (2010)More intensive LDL-lowering with statins produces further, dose-dependent reductions in major vascular events and all-cause mortality, with no evidence of harm from very low LDL levels.
- CTT 2019 older people (2019)Statins reduce major vascular events across all age groups including older people, though the evidence for benefit beyond age 75 without pre-existing vascular disease is less direct and being addressed by further trials.
- PCSK9/ezetimibe diabetes meta-analysis (2020)Neither PCSK9 inhibitors nor ezetimibe increase the risk of new-onset diabetes when added to guideline-directed medical therapy.
- CTT 2022 muscle (2022)Statins cause a small, mostly mild excess of muscle pain primarily in the first year of treatment, with over 90% of muscle symptom reports in statin users not actually due to the statin, and this risk is far outweighed by cardiovascular benefits.
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