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
- PMID: 22607822
- PMCID: PMC3437972
- DOI: 10.1016/S0140-6736(12)60367-5
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
Abstract
Background: Statins reduce LDL cholesterol and prevent vascular events, but their net effects in people at low risk of vascular events remain uncertain.
Methods: This meta-analysis included individual participant data from 22 trials of statin versus control (n=134,537; mean LDL cholesterol difference 1·08 mmol/L; median follow-up 4·8 years) and five trials of more versus less statin (n=39,612; difference 0·51 mmol/L; 5·1 years). Major vascular events were major coronary events (ie, non-fatal myocardial infarction or coronary death), strokes, or coronary revascularisations. Participants were separated into five categories of baseline 5-year major vascular event risk on control therapy (no statin or low-intensity statin) (<5%, ≥5% to <10%, ≥10% to <20%, ≥20% to <30%, ≥30%); in each, the rate ratio (RR) per 1·0 mmol/L LDL cholesterol reduction was estimated.
Findings: 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. The proportional reduction in major vascular events was at least as big in the two lowest risk categories as in the higher risk categories (RR per 1·0 mmol/L reduction 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), which reflected significant reductions in these two lowest risk categories in major coronary events (RR 0·57, 99% CI 0·36-0·89, p=0·0012, and 0·61, 99% CI 0·50-0·74, p<0·0001) and in coronary revascularisations (RR 0·52, 99% CI 0·35-0·75, and 0·63, 99% CI 0·51-0·79; both p<0·0001). For stroke, the reduction in risk in participants with 5-year risk of major vascular events lower than 10% (RR per 1·0 mmol/L LDL cholesterol reduction 0·76, 99% CI 0·61-0·95, p=0·0012) was also similar to that seen in higher risk categories (trend p=0·3). 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. 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.
Interpretation: In individuals with 5-year risk of major vascular events lower than 10%, each 1 mmol/L reduction in LDL cholesterol produced an absolute reduction in major vascular events of about 11 per 1000 over 5 years. This benefit greatly exceeds any known hazards of statin therapy. Under present guidelines, such individuals would not typically be regarded as suitable for LDL-lowering statin therapy. The present report suggests, therefore, that these guidelines might need to be reconsidered.
Funding: British Heart Foundation; UK Medical Research Council; Cancer Research UK; European Community Biomed Programme; Australian National Health and Medical Research Council; National Heart Foundation, Australia.
Copyright © 2012 Elsevier Ltd. All rights reserved.
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Comment in
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Statins for all by the age of 50 years?Lancet. 2012 Aug 11;380(9841):545-7. doi: 10.1016/S0140-6736(12)60694-1. Epub 2012 May 17. Lancet. 2012. PMID: 22607823 No abstract available.
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Vascular disease: Even low-risk individuals can benefit from statin therapy.Nat Rev Cardiol. 2012 Jun 5;9(7):371. doi: 10.1038/nrcardio.2012.79. Nat Rev Cardiol. 2012. PMID: 22665328 No abstract available.
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ACP Journal Club. Meta-analysis: lowering LDL-C levels using statins reduces major vascular events regardless of baseline risk.Ann Intern Med. 2012 Oct 16;157(8):JC4-2. doi: 10.7326/0003-4819-157-8-201210160-02002. Ann Intern Med. 2012. PMID: 23070504 No abstract available.
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Statin-induced lowering of LDL cholesterol associated with a reduced risk for cardiovascular events, not likely outweighed by the risk of diabetes, for people at low short-term risk of cardiovascular disease.Evid Based Med. 2013 Aug;18(4):142-3. doi: 10.1136/eb-2012-101028. Epub 2012 Nov 2. Evid Based Med. 2013. PMID: 23125231 No abstract available.
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Statins for people at low risk of cardiovascular disease.Lancet. 2012 Nov 24;380(9856):1814; author reply 1817-8. doi: 10.1016/S0140-6736(12)62020-0. Lancet. 2012. PMID: 23177692 No abstract available.
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Statins for people at low risk of cardiovascular disease.Lancet. 2012 Nov 24;380(9856):1814-5; author reply 1817-8. doi: 10.1016/S0140-6736(12)62021-2. Lancet. 2012. PMID: 23177693 No abstract available.
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Statins for people at low risk of cardiovascular disease.Lancet. 2012 Nov 24;380(9856):1815; author reply 1817-8. doi: 10.1016/S0140-6736(12)62022-4. Lancet. 2012. PMID: 23177694 No abstract available.
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Statins for people at low risk of cardiovascular disease.Lancet. 2012 Nov 24;380(9856):1815-6; author reply 1817-8. doi: 10.1016/S0140-6736(12)62023-6. Lancet. 2012. PMID: 23177695 No abstract available.
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Statins for people at low risk of cardiovascular disease.Lancet. 2012 Nov 24;380(9856):1816; author reply 1817-8. doi: 10.1016/S0140-6736(12)62024-8. Lancet. 2012. PMID: 23177696 No abstract available.
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Statins for people at low risk of cardiovascular disease.Lancet. 2012 Nov 24;380(9856):1816; author reply 1817-8. doi: 10.1016/S0140-6736(12)62025-X. Lancet. 2012. PMID: 23177697 No abstract available.
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Statins for people at low risk of cardiovascular disease.Lancet. 2012 Nov 24;380(9856):1817; author reply 1817-8. doi: 10.1016/S0140-6736(12)62026-1. Lancet. 2012. PMID: 23177699 No abstract available.
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Statins for people at low risk of cardiovascular disease.Lancet. 2012 Nov 24;380(9856):1818. doi: 10.1016/S0140-6736(12)62028-5. Lancet. 2012. PMID: 23177700 No abstract available.
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[Statin therapy in low-risk cardiac patients is particularly effective].Dtsch Med Wochenschr. 2012 Oct;137(42):2136. doi: 10.1055/s-0032-1328976. Dtsch Med Wochenschr. 2012. PMID: 23227522 German. No abstract available.
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Evolocumab and clinical outcomes in patients with cardiovascular disease.J R Coll Physicians Edinb. 2017 Jun;47(2):153-155. doi: 10.4997/JRCPE.2017.212. J R Coll Physicians Edinb. 2017. PMID: 28675189 No abstract available.
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