Comparative Effectiveness of Statins on Non-HDL Cholesterol by Type and Intensity in People with Diabetes and at Risk of Cardiovascular Disease: Systematic Review and Network Meta-Analysis

Objective: To compare the efficacy of different statin therapies by intensity for prevention of cardiovascular disease (CVD) in people with diabetes according to non-high-density lipoprotein cholesterol (non-HDL-C). Design: Systematic review and network meta-analysis. Data Sources: Searches in MEDLINE, Cochrane Central Register of Controlled Trials, and EMBASE until December 2021. Review Methods: Randomised controlled trials comparing different type(s) and intensity of statins including placebo in adults with diabetes mellitus (type 1 or 2) were included. Main Outcome Measure: Primary outcome was non-HDL-C, calculated using total cholesterol and high-density lipoprotein cholesterol measures. Secondary outcomes include low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), 3-point major cardiovascular events (MACE) (non-fatal stroke, non-fatal myocardial infarction, and cardiovascular related death) and discontinuations due to adverse events. Data Synthesis: A Bayesian network meta-analysis of statin intensity (low, moderate, or high) using random-effects evaluated treatment effect on non-HDL-C through mean difference and 95% credible intervals. Subgroup analysis of patients at greater risk of MACE was compared with patients at low/moderate risk. The Confidence In Network Meta-Analysis (CINeMA) framework was applied to ensure the certainty of evidence. Results: Forty-two trials randomizing 20,193 adults of which 11,698 were included in the meta-analysis. Compared to placebo, the greatest reductions in non-HDL-C were observed in Rosuvastatin at high (-2.31 mmol/L, 95% credible interval: -3.39 to -1.21) and moderate intensities (-2.27 mmol/L, -3.00 to -1.49), and Simvastatin (-2.26 mmol/L, -2.99 to -1.51) and Atorvastatin (-2.20 mmol/L, -2.69 to -1.70) at high intensity. Atorvastatin and Simvastatin at any intensity and Pravastatin at low intensity were also effective at reducing non-HDL-C. In 4,670 patients at greater risk of a MACE, Atorvastatin at high intensity was best ranked (-1.98 mmol/L, -4.16 ...