Document Detail

Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins.
MedLine Citation:
PMID:  16214597     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Results of previous randomised trials have shown that interventions that lower LDL cholesterol concentrations can significantly reduce the incidence of coronary heart disease (CHD) and other major vascular events in a wide range of individuals. But each separate trial has limited power to assess particular outcomes or particular categories of participant.
METHODS: A prospective meta-analysis of data from 90,056 individuals in 14 randomised trials of statins was done. Weighted estimates were obtained of effects on different clinical outcomes per 1.0 mmol/L reduction in LDL cholesterol.
FINDINGS: During a mean of 5 years, there were 8186 deaths, 14,348 individuals had major vascular events, and 5103 developed cancer. Mean LDL cholesterol differences at 1 year ranged from 0.35 mmol/L to 1.77 mmol/L (mean 1.09) in these trials. There was a 12% proportional reduction in all-cause mortality per mmol/L reduction in LDL cholesterol (rate ratio [RR] 0.88, 95% CI 0.84-0.91; p<0.0001). This reflected a 19% reduction in coronary mortality (0.81, 0.76-0.85; p<0.0001), and non-significant reductions in non-coronary vascular mortality (0.93, 0.83-1.03; p=0.2) and non-vascular mortality (0.95, 0.90-1.01; p=0.1). There were corresponding reductions in myocardial infarction or coronary death (0.77, 0.74-0.80; p<0.0001), in the need for coronary revascularisation (0.76, 0.73-0.80; p<0.0001), in fatal or non-fatal stroke (0.83, 0.78-0.88; p<0.0001), and, combining these, of 21% in any such major vascular event (0.79, 0.77-0.81; p<0.0001). The proportional reduction in major vascular events differed significantly (p<0.0001) according to the absolute reduction in LDL cholesterol achieved, but not otherwise. These benefits were significant within the first year, but were greater in subsequent years. Taking all years together, the overall reduction of about one fifth per mmol/L LDL cholesterol reduction translated into 48 (95% CI 39-57) fewer participants having major vascular events per 1000 among those with pre-existing CHD at baseline, compared with 25 (19-31) per 1000 among participants with no such history. There was no evidence that statins increased the incidence of cancer overall (1.00, 0.95-1.06; p=0.9) or at any particular site.
INTERPRETATION: Statin therapy can safely reduce the 5-year incidence of major coronary events, coronary revascularisation, and stroke by about one fifth per mmol/L reduction in LDL cholesterol, largely irrespective of the initial lipid profile or other presenting characteristics. The absolute benefit relates chiefly to an individual's absolute risk of such events and to the absolute reduction in LDL cholesterol achieved. These findings reinforce the need to consider prolonged statin treatment with substantial LDL cholesterol reductions in all patients at high risk of any type of major vascular event.
C Baigent; A Keech; P M Kearney; L Blackwell; G Buck; C Pollicino; A Kirby; T Sourjina; R Peto; R Collins; R Simes;
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Publication Detail:
Type:  Journal Article; Meta-Analysis; Research Support, Non-U.S. Gov't     Date:  2005-09-27
Journal Detail:
Title:  Lancet     Volume:  366     ISSN:  1474-547X     ISO Abbreviation:  Lancet     Publication Date:  2005 Oct 
Date Detail:
Created Date:  2005-10-10     Completed Date:  2005-10-21     Revised Date:  2014-02-19    
Medline Journal Info:
Nlm Unique ID:  2985213R     Medline TA:  Lancet     Country:  England    
Other Details:
Languages:  eng     Pagination:  1267-78     Citation Subset:  AIM; IM    
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MeSH Terms
Cause of Death
Cholesterol, LDL / blood*
Coronary Disease / mortality,  prevention & control
Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects,  therapeutic use*
Hypercholesterolemia / drug therapy*
Myocardial Infarction / mortality
Randomized Controlled Trials as Topic
Risk Factors
Stroke / mortality,  prevention & control
Treatment Outcome
Grant Support
MC_U137686849//Medical Research Council; //Wellcome Trust
Reg. No./Substance:
0/Cholesterol, LDL; 0/Hydroxymethylglutaryl-CoA Reductase Inhibitors
Comment In:
Evid Based Cardiovasc Med. 2006 Mar;10(1):8-10   [PMID:  16530655 ]
Lancet. 2006 Feb 11;367(9509):469-70; author reply 470-1   [PMID:  16473115 ]
Curr Atheroscler Rep. 2007 Jan;9(1):8-9   [PMID:  17169240 ]
ACP J Club. 2006 May-Jun;144(3):62   [PMID:  16646606 ]
Lancet. 2006 Feb 11;367(9509):469; author reply 470-1   [PMID:  16473116 ]
Erratum In:
Lancet. 2005 Oct 15-21;366(9494):1358
Lancet. 2008 Jun 21;371(9630):2084

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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