Relative Effect of Current Intensive Lipid-Lowering Drugs on Cardiovascular Outcomes in Secondary Prevention　― A Meta-Analysis of 12 Randomized Trials

Background:We aimed to investigate the comparative cardiovascular benefits of high-dose statin, ezetimibe-statin, and PCSK9 inhibitor-statin treatments in secondary prevention patients.Methods and Results:We selected 12 randomized controlled trials (n=131,978 patients) using PubMed and Embase (inception–June 1, 2018). Subgroup differences were explored by meta-regression and Cochran Q test. The relative effects of high-dose statin, ezetimibe-statin, and PCSK9 inhibitor-statin on major cardiovascular events (MACE), and revascularization were varied and decreased gradually, of which high-dose statin resulted in lower risk of MACE and revascularization than PCSK9 inhibitor-statin per 1 mmol/L reduction of low-density lipoprotein cholesterol (LDL-C): risk ratio (RR) for MACE, 0.86 (95% confidence interval (CI), 0.81–0.90) for high-dose statin, 0.90 (95% CI, 0.83–0.96) for ezetimibe-statin, and 0.94 (95% CI, 0.92–0.96) for PCSK9 inhibitor-statin; RR for revascularization, 0.84 (95% CI, 0.77–0.90) for high-dose statin, 0.91 (95% CI, 0.81–1.00) for ezetimibe-statin, and 0.94 (95% CI, 0.90–0.97) for PCSK9 inhibitor-statin. Similar relative effects of intensive lipid-lowering treatment were also observed in analyses of myocardial infarction and stroke, although no significant difference between groups was identified.Conclusions:In secondary prevention patients, the relative benefits of high-dose statin, ezetimibe-statin, and PCSK9 inhibitor-statin treatments were varied and decreased gradually, of which high-dose statin was significantly superior to PCSK9 inhibitor-statin for improving MACE and revascularization per 1 mmol/L reduction of LDL-C.