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Comparative benefits of statins in the primary and secondary prevention of major coronary events and all-cause mortality: a network meta-analysis of placebo-controlled and active-comparator trials.
Eur J Prev Cardiol 2013; 20(4):641-57EJ

Abstract

BACKGROUND

The extent to which individual statins vary in terms of clinical outcomes across all populations, in addition to secondary and primary prevention has not been studied extensively in meta-analyses.

METHODS

We systematically studied 199,721 participants in 92 placebo-controlled and active-comparator trials comparing atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin, and simvastatin in participants with, or at risk of developing, cardiovascular disease. We performed pairwise and network meta-analyses for major coronary events and all-cause mortality outcomes, taking into account the dose differences across trials. Systematic review registration: PROSPERO 2011:CRD42011001470.

RESULTS

There were only a few trials that evaluated fluvastatin. Most frequent comparisons occurred between pravastatin and placebo, atorvastatin and placebo, and rosuvastatin and atorvastatin. No trial directly compared all six statins to each other. Across all populations, statins were significantly more effective than control in reducing all-cause mortality (OR 0.87, 95% credible interval 0.82-0.92) and major coronary events (OR 0.69, 95% CI 0.64-0.75). In terms of reducing major coronary events, atorvastatin (OR 0.66, 95% CI 0.48-0.94) and fluvastatin (OR 0.59, 95% CI 0.36-0.95) were significantly more effective than rosuvastatin at comparable doses. In participants with cardiovascular disease, statins significantly reduced deaths (OR 0.82, 95% CI 0.75-0.90) and major coronary events (OR 0.69, 95% CI 0.62-0.77). Atorvastatin was significantly more effective than pravastatin (OR 0.65, 95% CI 0.43-0.99) and simvastatin (OR 0.68, 95% CI 0.38-0.98) for secondary prevention of major coronary events. In primary prevention, statins significantly reduced deaths (OR 0.91, 95% CI 0.83-0.99) and major coronary events (OR 0.69, 95% CI 0.61-0.79) with no differences among individual statins. Across all populations, atorvastatin (80%), fluvastatin (79%), and simvastatin (62%) had the highest overall probability of being the best treatment in terms of both outcomes. Higher doses of atorvastatin and fluvastatin had the highest number of significant differences in preventing major coronary events compared with other statins. No significant heterogeneity or inconsistency was detected.

CONCLUSIONS

Statins significantly reduce the incidence of all-cause mortality and major coronary events as compared to control in both secondary and primary prevention. This analysis provides evidence for potential differences between individual statins, which are not fully explained by their low-density lipoprotein cholesterol-reducing effects. The observed differences between statins should be investigated in future prospective studies.

Authors+Show Affiliations

Department of Social Policy, London School of Economics & Political Science, London, UK. h.naci@lse.ac.ukNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Meta-Analysis
Review
Systematic Review

Language

eng

PubMed ID

23447425

Citation

Naci, Huseyin, et al. "Comparative Benefits of Statins in the Primary and Secondary Prevention of Major Coronary Events and All-cause Mortality: a Network Meta-analysis of Placebo-controlled and Active-comparator Trials." European Journal of Preventive Cardiology, vol. 20, no. 4, 2013, pp. 641-57.
Naci H, Brugts JJ, Fleurence R, et al. Comparative benefits of statins in the primary and secondary prevention of major coronary events and all-cause mortality: a network meta-analysis of placebo-controlled and active-comparator trials. Eur J Prev Cardiol. 2013;20(4):641-57.
Naci, H., Brugts, J. J., Fleurence, R., Tsoi, B., Toor, H., & Ades, A. E. (2013). Comparative benefits of statins in the primary and secondary prevention of major coronary events and all-cause mortality: a network meta-analysis of placebo-controlled and active-comparator trials. European Journal of Preventive Cardiology, 20(4), pp. 641-57. doi:10.1177/2047487313480435.
Naci H, et al. Comparative Benefits of Statins in the Primary and Secondary Prevention of Major Coronary Events and All-cause Mortality: a Network Meta-analysis of Placebo-controlled and Active-comparator Trials. Eur J Prev Cardiol. 2013;20(4):641-57. PubMed PMID: 23447425.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparative benefits of statins in the primary and secondary prevention of major coronary events and all-cause mortality: a network meta-analysis of placebo-controlled and active-comparator trials. AU - Naci,Huseyin, AU - Brugts,Jasper J, AU - Fleurence,Rachael, AU - Tsoi,Bernice, AU - Toor,Harleen, AU - Ades,A E, Y1 - 2013/02/27/ PY - 2013/3/1/entrez PY - 2013/3/1/pubmed PY - 2014/2/14/medline KW - Meta-analysis KW - mixed treatment comparison KW - prevention of coronary heart disease KW - statins KW - systematic review SP - 641 EP - 57 JF - European journal of preventive cardiology JO - Eur J Prev Cardiol VL - 20 IS - 4 N2 - BACKGROUND: The extent to which individual statins vary in terms of clinical outcomes across all populations, in addition to secondary and primary prevention has not been studied extensively in meta-analyses. METHODS: We systematically studied 199,721 participants in 92 placebo-controlled and active-comparator trials comparing atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin, and simvastatin in participants with, or at risk of developing, cardiovascular disease. We performed pairwise and network meta-analyses for major coronary events and all-cause mortality outcomes, taking into account the dose differences across trials. Systematic review registration: PROSPERO 2011:CRD42011001470. RESULTS: There were only a few trials that evaluated fluvastatin. Most frequent comparisons occurred between pravastatin and placebo, atorvastatin and placebo, and rosuvastatin and atorvastatin. No trial directly compared all six statins to each other. Across all populations, statins were significantly more effective than control in reducing all-cause mortality (OR 0.87, 95% credible interval 0.82-0.92) and major coronary events (OR 0.69, 95% CI 0.64-0.75). In terms of reducing major coronary events, atorvastatin (OR 0.66, 95% CI 0.48-0.94) and fluvastatin (OR 0.59, 95% CI 0.36-0.95) were significantly more effective than rosuvastatin at comparable doses. In participants with cardiovascular disease, statins significantly reduced deaths (OR 0.82, 95% CI 0.75-0.90) and major coronary events (OR 0.69, 95% CI 0.62-0.77). Atorvastatin was significantly more effective than pravastatin (OR 0.65, 95% CI 0.43-0.99) and simvastatin (OR 0.68, 95% CI 0.38-0.98) for secondary prevention of major coronary events. In primary prevention, statins significantly reduced deaths (OR 0.91, 95% CI 0.83-0.99) and major coronary events (OR 0.69, 95% CI 0.61-0.79) with no differences among individual statins. Across all populations, atorvastatin (80%), fluvastatin (79%), and simvastatin (62%) had the highest overall probability of being the best treatment in terms of both outcomes. Higher doses of atorvastatin and fluvastatin had the highest number of significant differences in preventing major coronary events compared with other statins. No significant heterogeneity or inconsistency was detected. CONCLUSIONS: Statins significantly reduce the incidence of all-cause mortality and major coronary events as compared to control in both secondary and primary prevention. This analysis provides evidence for potential differences between individual statins, which are not fully explained by their low-density lipoprotein cholesterol-reducing effects. The observed differences between statins should be investigated in future prospective studies. SN - 2047-4881 UR - https://www.unboundmedicine.com/medline/citation/23447425/Comparative_benefits_of_statins_in_the_primary_and_secondary_prevention_of_major_coronary_events_and_all_cause_mortality:_a_network_meta_analysis_of_placebo_controlled_and_active_comparator_trials_ L2 - http://journals.sagepub.com/doi/full/10.1177/2047487313480435?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -