The benefits of statins in people without established cardiovascular disease but with cardiovascular risk factors: meta-analysis of randomised controlled trials - PubMed (original) (raw)

Review

doi: 10.1136/bmj.b2376.

T Yetgin, S E Hoeks, A M Gotto, J Shepherd, R G J Westendorp, A J M de Craen, R H Knopp, H Nakamura, P Ridker, R van Domburg, J W Deckers

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Review

The benefits of statins in people without established cardiovascular disease but with cardiovascular risk factors: meta-analysis of randomised controlled trials

J J Brugts et al. BMJ. 2009.

Abstract

Objectives: To investigate whether statins reduce all cause mortality and major coronary and cerebrovascular events in people without established cardiovascular disease but with cardiovascular risk factors, and whether these effects are similar in men and women, in young and older (>65 years) people, and in people with diabetes mellitus.

Design: Meta-analysis of randomised trials.

Data sources: Cochrane controlled trials register, Embase, and Medline. Data abstraction Two independent investigators identified studies on the clinical effects of statins compared with a placebo or control group and with follow-up of at least one year, at least 80% or more participants without established cardiovascular disease, and outcome data on mortality and major cardiovascular disease events. Heterogeneity was assessed using the Q and I(2) statistics. Publication bias was assessed by visual examination of funnel plots and the Egger regression test.

Results: 10 trials enrolled a total of 70 388 people, of whom 23 681 (34%) were women and 16 078 (23%) had diabetes mellitus. Mean follow-up was 4.1 years. Treatment with statins significantly reduced the risk of all cause mortality (odds ratio 0.88, 95% confidence interval 0.81 to 0.96), major coronary events (0.70, 0.61 to 0.81), and major cerebrovascular events (0.81, 0.71 to 0.93). No evidence of an increased risk of cancer was observed. There was no significant heterogeneity of the treatment effect in clinical subgroups.

Conclusion: In patients without established cardiovascular disease but with cardiovascular risk factors, statin use was associated with significantly improved survival and large reductions in the risk of major cardiovascular events.

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Conflict of interest statement

Competing interests: AMG is a consultant for Genentech, Kowa, Martek, Merck, and Merck/Schering-Plough, and serves on the board of directors for Aegerion and Arisaph. He is a member of DuPont’s health advisory board and serves on the data safety monitoring board for Novartis. JS carried out consultancy work and receives support for research from Bristol-Myers Squibb. RGJW receives support for research from Bristol-Myers Squibb. HN has received travel grants and speaking honorariums from Sankyo. RHK has received research fees and speaking honorariums from Pfizer. PR has received research grant support from the National Heart Lung and Blood Institute, the National Cancer Institute, the Donald W Reynolds Foundation, the Leducq Foundation, Astra-Zeneca, Novartis, Merck, Abbott, Roche, and Sanofi-Aventis; consulting fees and lecture fees from Astra-Zeneca, Novartis, Merck-Schering Plough, Sanofi-Aventis, ISIS, and Vascular Biogenics; and is listed as a co-inventor on patents held by the Brigham and Women’s Hospital that relate to the use of inflammatory biomarkers in cardiovascular disease. These patents have been licensed to Siemens and Astra-Zeneca.

Figures

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Fig 1 Flow of article selection in trial

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Fig 2 Odds ratios (95% confidence intervals) for all cause mortality, major coronary events, major cerebrovascular events, and incidence of cancer. (Mortality risk based on mean follow-up of 4.1 years, with data from nine trials, and 67 476 patients free of cardiovascular disease (no data available from HPS diabetic armw5). Risk of coronary events based on mean follow-up of 4.9 years, with data from eight trials, and 50 681 patients free of cardiovascular disease (no data available from ASPENw3 and JUPITERw1). Risk of cerebrovascular events based on mean follow-up of 4.1 years, with data from nine trials, and 67 476 patients free of cardiovascular disease (no data available from HPS diabetic arm). Risk of cancer based on mean follow-up of 3.9 years, with data from six trials, and 52 027 patients free of cardiovascular disease (no data available from HPS, ASCOT,w10 PROSPER,w6 and ASPEN). See footnote to table 1 for full titles of studies. *Measures of heterogeneity

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Fig 3 Odds ratios (95% confidence intervals) for clinically defined subgroups of sex, age, and diabetes for end points of all cause mortality, major coronary events, major cerebrovascular events, and cancer. Subgroup data are obtained from AFCAPS,w8 PROSPER,w6 ASPEN,w3 MEGA,w2 and JUPITERw1, and for mortality and coronary events from ALLHAT-LLT.w7 We had complete mortality data from all six trials for sex; for age, no data from PROSPER on age<65; for diabetes, no data from ASPEN and AFCAPS on participants without diabetes, and no data from AFCAPS and JUPITER on participants with diabetes. For cardiovascular events, studies included in subgroup analysis were same as for mortality, except no data from AFCAPS for age groups. For cerebrovascular disease, no data from AFCAPS and ALLHAT for all subgroups; also no data from PROSPER on age <65, from ASPEN for participants without diabetes, and from JUPITER for participants with diabetes. For cancer no subgroup data were obtained from ALLHAT; also no data for age <65 from PROSPER, for participants without diabetes from AFCAPS and ASPEN, and for participants with diabetes from JUPITER and AFCAPS. See footnote to table 1 for full titles of studies

Comment in

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