Ades all-cause mortality : a network meta-analysis of placebo-controlled and active-comparator trials

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. London School of Economics & Political Science, London, UK Erasmus Medical Centre Rotterdam, The Netherlands Patient-Centered Outcomes Research Institute, Washington, DC, USA University of Bristol, Bristol, UK Corresponding author: Huseyin Naci, LSE Health and Social Care, Department of Social Policy, London School of Economics & Political Science, 20 Houghton Street, London, WC2A 2AE, UK. Email: h.naci@lse.ac. uk European Journal of Preventive Cardiology 0(00) 1–17 ! The European Society of Cardiology 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/2047487313480435 ejpc.sagepub.com at St Petersburg State University on December 8, 2013 cpr.sagepub.com Downloaded from XML Template (2013) [25.2. 2013–4:54pm] [1–17] //blrnas3/cenpro/ApplicationFiles/Journals/SAGE/3B2/CPRJ/Vol00000/130176/APPFile/SG-CPRJ130176.3d (CPR) [PREPRINTER stage]