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Dose-comparative effects of different statins on serum lipid levels: a network meta-analysis of 256,827 individuals in 181 randomized controlled trials.
Eur J Prev Cardiol 2013; 20(4):658-70EJ

Abstract

AIMS

The extent to which individual statins vary in terms of their impact on serum lipid levels has been studied mainly on the basis of placebo-controlled trials. Our objective was to review and quantify the dose-comparative effects of different statins on serum lipid levels using both placebo- and active-comparator trials.

METHODS

We systematically reviewed randomized trials evaluating different statins in participants with, or at risk of developing, cardiovascular disease. We performed random-effects Bayesian network meta-analyses to quantify the the relative potency of individual statins across all possible dose combinations using both direct and indirect evidence. Dose-comparative effects were determined by estimating the mean change from baseline in serum lipids as compared to control treatment. (systematic review registration: PROSPERO 2011:CRD42011001470).

RESULTS

We included 181 placebo-controlled and active-comparator trials including 256,827 individuals. There were 83 two-armed placebo-controlled trials and the remaining 98 were two- or multi-armed active-comparator trials. All statins reduced serum LDL and total cholesterol levels: higher doses resulted in higher reductions in pretreatment LDL and total cholesterol concentrations. In absolute terms, all statins significantly reduced LDL cholesterol levels as compared to control treatment from average baseline levels of approximately 150 mg/dl, except for fluvastatin at ≤20 mg/day and lovastatin at ≤10 mg/day. Atorvastatin, rosuvastatin, and simvastatin were broadly equivalent in terms of their LDL cholesterol-lowering effects. Dose-comparative effects of indivudual statins were not different between those with and without coronary heart disease at baseline. According to meta-regression analyses, LDL cholesterol-lowering effects of individual statins were not impacted by differences across trials in terms of baseline mean age and proportion of women as trial participants. Pretreatment LDL cholesterol concentrations had a marginally statistically significant effect on LDL cholesterol change from baseline. Mean differences from baseline in HDL cholesterol as compared to control treatment was not significant for any statin-dose combination.

CONCLUSIONS

The findings of this comprehensive review provide supporting evidence for the dose-response relationship of statins in reducing LDL and total cholesterol. The LDL cholesterol-reducing effects of some statins appear less pronounced than the findings of previous meta-analyses, which is particularly the case for the high-dose formulations of atorvastatin and rosuvastatin. The most consistent evidence for a combined reduction in both LDL and total cholesterol was achieved with atorvastatin at >40 mg/day, rosuvastatin at >10 mg/day, and simvastatin at >40 mg/day, which appear equivalent in terms of their LDL and total cholesterol-reducing effects.

Authors+Show Affiliations

Department of Social Policy, London School of Economics & Political Science, London, UK. h.naci@lse.ac.uk

Pub Type(s)

Journal Article
Meta-Analysis
Review
Systematic Review

Language

eng

PubMed ID

23529608

Citation

Naci, Huseyin, et al. "Dose-comparative Effects of Different Statins On Serum Lipid Levels: a Network Meta-analysis of 256,827 Individuals in 181 Randomized Controlled Trials." European Journal of Preventive Cardiology, vol. 20, no. 4, 2013, pp. 658-70.
Naci H, Brugts JJ, Fleurence R, et al. Dose-comparative effects of different statins on serum lipid levels: a network meta-analysis of 256,827 individuals in 181 randomized controlled trials. Eur J Prev Cardiol. 2013;20(4):658-70.
Naci, H., Brugts, J. J., Fleurence, R., & Ades, A. E. (2013). Dose-comparative effects of different statins on serum lipid levels: a network meta-analysis of 256,827 individuals in 181 randomized controlled trials. European Journal of Preventive Cardiology, 20(4), pp. 658-70. doi:10.1177/2047487313483600.
Naci H, et al. Dose-comparative Effects of Different Statins On Serum Lipid Levels: a Network Meta-analysis of 256,827 Individuals in 181 Randomized Controlled Trials. Eur J Prev Cardiol. 2013;20(4):658-70. PubMed PMID: 23529608.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dose-comparative effects of different statins on serum lipid levels: a network meta-analysis of 256,827 individuals in 181 randomized controlled trials. AU - Naci,Huseyin, AU - Brugts,Jasper J, AU - Fleurence,Rachael, AU - Ades,A E, Y1 - 2013/03/25/ PY - 2013/3/27/entrez PY - 2013/3/27/pubmed PY - 2014/2/14/medline KW - Statins KW - cholesterol KW - indirect comparison KW - meta-analysis KW - mixed treatment comparison KW - systematic review SP - 658 EP - 70 JF - European journal of preventive cardiology JO - Eur J Prev Cardiol VL - 20 IS - 4 N2 - AIMS: The extent to which individual statins vary in terms of their impact on serum lipid levels has been studied mainly on the basis of placebo-controlled trials. Our objective was to review and quantify the dose-comparative effects of different statins on serum lipid levels using both placebo- and active-comparator trials. METHODS: We systematically reviewed randomized trials evaluating different statins in participants with, or at risk of developing, cardiovascular disease. We performed random-effects Bayesian network meta-analyses to quantify the the relative potency of individual statins across all possible dose combinations using both direct and indirect evidence. Dose-comparative effects were determined by estimating the mean change from baseline in serum lipids as compared to control treatment. (systematic review registration: PROSPERO 2011:CRD42011001470). RESULTS: We included 181 placebo-controlled and active-comparator trials including 256,827 individuals. There were 83 two-armed placebo-controlled trials and the remaining 98 were two- or multi-armed active-comparator trials. All statins reduced serum LDL and total cholesterol levels: higher doses resulted in higher reductions in pretreatment LDL and total cholesterol concentrations. In absolute terms, all statins significantly reduced LDL cholesterol levels as compared to control treatment from average baseline levels of approximately 150 mg/dl, except for fluvastatin at ≤20 mg/day and lovastatin at ≤10 mg/day. Atorvastatin, rosuvastatin, and simvastatin were broadly equivalent in terms of their LDL cholesterol-lowering effects. Dose-comparative effects of indivudual statins were not different between those with and without coronary heart disease at baseline. According to meta-regression analyses, LDL cholesterol-lowering effects of individual statins were not impacted by differences across trials in terms of baseline mean age and proportion of women as trial participants. Pretreatment LDL cholesterol concentrations had a marginally statistically significant effect on LDL cholesterol change from baseline. Mean differences from baseline in HDL cholesterol as compared to control treatment was not significant for any statin-dose combination. CONCLUSIONS: The findings of this comprehensive review provide supporting evidence for the dose-response relationship of statins in reducing LDL and total cholesterol. The LDL cholesterol-reducing effects of some statins appear less pronounced than the findings of previous meta-analyses, which is particularly the case for the high-dose formulations of atorvastatin and rosuvastatin. The most consistent evidence for a combined reduction in both LDL and total cholesterol was achieved with atorvastatin at >40 mg/day, rosuvastatin at >10 mg/day, and simvastatin at >40 mg/day, which appear equivalent in terms of their LDL and total cholesterol-reducing effects. SN - 2047-4881 UR - https://www.unboundmedicine.com/medline/citation/23529608/Dose_comparative_effects_of_different_statins_on_serum_lipid_levels:_a_network_meta_analysis_of_256827_individuals_in_181_randomized_controlled_trials_ L2 - http://journals.sagepub.com/doi/full/10.1177/2047487313483600?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -