Efficacy and safety of statin treatment for cardiovascular disease: a network meta-analysis of 170 255 patients from 76 randomized trials

Background: Statins represent the largest selling class of cardiovascular drug in the world. Previous randomized trials (RCTs) have demonstrated important clinical benefits with statin therapy. Aim: We combined evidence from all RCTs comparing a statin with placebo or usual care among patients with and without prior coronary heart disease (CHD) to determine clinical outcomes. Design: We searched independently, in duplicate, 12 electronic databases (from inception to August 2010), including full text journal content databases, to identify all statin versus inert control RCTs. We included RCTs of any statin versus any non-drug control in any populations. We abstracted data in duplicate on reported major clinical events and adverse events. We performed a random-effects meta-analysis and meta-regression. We performed a mixed treatment comparison using Bayesian methods. Results: We included a total of 76 RCTs involving 170 255 participants. There were a total of 14 878 deaths. Statin therapy reduced all-cause mortality, Relative Risk (RR) 0.90 [95% confidence interval (CI) 0.86-0.94, P ≤ 0.0001, I 2 = 17%]; cardiovascular disease (CVD) mortality (RR 0.80, 95% CI 0.74-0.87, P < 0.0001, I 2 = 27%); fatal myocardial infarction (MI) (RR 0.82, 95% CI 0.75-0.91, P < 0.0001, I 2 = 21%); non-fatal MI (RR 0.74, 95% CI 0.67-0.81, P ≤ 0.001, I 2 = 45%); revascularization (RR 0.76, 95% CI 0.70-0.81, P ≤ 0.0001); and a composite of fatal and non-fatal strokes (0.86, 95% CI 0.78-0.95, P = 0.004, I 2 = 41%). Adverse events were generally mild, but 17 RCTs reported on increased risk of development of incident diabetes [Odds Ratio (OR) 1.09; 95% CI 1.02-1.17, P = 0.001, I 2 = 11%]. Studies did not yield important differences across populations. We did not find any differing treatment effects between statins. Discussion: Statin therapies offer clear benefits across broad populations. As generic formulations become more available efforts to expand access should be a priorit

Pharmacotherapies for chronic obstructive pulmonary disease: a multiple treatment comparison meta-analysis

Edward J Mills1, Eric Druyts1, Isabella Ghement2, Milo A Puhan31Faculty of Health Sciences, University of Ottawa, Ottawa, Ontario, Canada; 2Ghement Statistical Consulting Company, Richmond, British Columbia, Canada; 3Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USABackground: Most patients with moderate and severe chronic obstructive pulmonary disease (COPD) receive long-acting bronchodilators (LABA) for symptom control. It is, however, unclear if and what drug treatments should be added to LABAs to reduce exacerbations, which is an important goal of COPD management. Since current guidelines cannot make strong recommendations yet, our aim was to determine the relative efficacy of existing treatments and combinations to reduce the risk for COPD exacerbations.Methods: We included randomized clinical trials (RCTs) evaluating long-acting &amp;szlig;2 agonists (LABA), long-acting muscarinic antagonists (LAMA), inhaled glucocorticosterioids (ICS), and the phosphodiesterase-4 (PDE4) inhibitor roflumilast, and combinations of these interventions in moderate to severe COPD populations. Our primary outcome was the event rate of exacerbations. We conducted a random-effects Bayesian mixed-treatment comparison (MTC) and applied several sensitivity analyses. In particular, we confirmed our findings using a binomial MTC analysis examining whether a patient experienced at least one exacerbation event or not during the trial. We also used an additive assumption to calculate the combined effects of treatments that were not included in the systematic review.Results: Twenty-six studies provided data on the total number of exacerbations and/or the mean annual rate of exacerbations among a combined 36,312 patients. There were a total of 10 treatment combinations in the MTC and 15 in the additive analysis. Compared with all other treatments, the combination of roflumilast plus LAMA exhibited the largest treatment effects, and had the highest probability (45%) of being the best first-line treatment. This was consistent whether applying the incidence rate analysis or the binomial analysis. When applying the additive assumption, most point estimates suggested that roflumilast may provide additional benefit by further reducing exacerbations.Conclusions: Using various meta-analytic approaches, our study demonstrates that depending on the choice of drug, combined treatments offer a therapeutic advantage.Keywords: exacerbations, MTC analysis, clinical trials, roflumilast&amp;nbsp

Multiple treatment comparison meta-analyses: a step forward into complexity

Edward J Mills1, Nick Bansback2,8, Isabella Ghement3, Kristian Thorlund4, Steven Kelly5, Milo A Puhan6, James Wright71Faculty of Health Sciences, University of Ottawa, Ottawa, ON, Canada; 2Centre for Health Evaluation and Outcomes Sciences (CHEOS), University of British Columbia, Vancouver, BC, Canada; 3Ghement Statistical Consulting Company, Richmond, BC, Canada; 4Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada; 5Department of Outcomes Research and Evidence Based Medicine, Pfizer Ltd, Walton Oaks, UK; 6Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA; 7Department of Oncology and Medicine, McMaster University, Hamilton, ON, Canada; 8School of Population and Public Health, University of British Columbia, Vancouver, BC, CanadaAbstract: The use of meta-analysis has become increasingly useful for clinical and policy decision making. A recent development in meta-analysis, multiple treatment comparison (MTC) meta-analysis, provides inferences on the comparative effectiveness of interventions that may have never been directly evaluated in clinical trials. This new approach may be confusing for clinicians and methodologists and raises specific challenges relevant to certain areas of medicine. This article addresses the methodological concepts of MTC meta-analysis, including issues of heterogeneity, choice of model, and adequacy of sample sizes. We address domain-specific challenges relevant to disciplines of medicine, including baseline risks of patient populations. We conclude that MTC meta-analysis is a useful tool in the context of comparative effectiveness and requires further study, as its utility and transparency will likely predict its uptake by the research and clinical community.Keywords: network, multiple treatment comparison, mixed treatment comparison, meta-analysi

Efficacy and safety of statin treatment for cardiovascular disease : a network meta-analysis of 170 255 patients from 76 randomized trials

Statins represent the largest selling class of cardiovascular drug in the world. Previous randomized trials (RCTs) have demonstrated important clinical benefits with statin therapy