Lipid levels and major adverse cardiovascular events in patients initiated on statins for primary prevention: an international population-based cohort study protocol

Abstract

Background: Clinical guidelines recommend specific targets for low-density lipoprotein cholesterol (LDL-C) and non–high-density lipoprotein cholesterol (non–HDL-C) for primary prevention of cardiovascular disease (CVD). Aim: To assess whether lower concentrations of LDL-C and non–HDL-C are associated with a reduced risk of major adverse cardiovascular events (MACE) in primary prevention of CVD. Individual variability in lipid response to statin therapy requires assessment this association in diverse populations. Design & setting International, new-user, cohort study, using data from three electronic health record databases from three regions: Clinical Practice Research Datalink, United Kingdom; PREDICT-CVD, New Zealand; and the Clinical Data and Analysis Reporting System, Hong Kong. Ethical approval has been obtained or waived as per local ethics policies. Method New statin users without a history of atherosclerotic CVD, heart failure, or chronic kidney disease, with baseline and follow-up lipid levels will be eligible for inclusion. Patients will be classified according to LDL-C (<1.4, 1.4 to 1.7, 1.8 to 2.5, ≥2.6 mmol/L) and non–HDL-C (<2.2, 2.2 to 2.5, 2.6 to 3.3, ≥3.4 mmol/L) concentrations twenty-four months after initiating statin therapy. The primary outcome of interest is MACE, defined as the first occurrence of coronary heart disease, stroke, or cardiovascular death. Secondary outcomes include all-cause mortality and the individual components of MACE. Sensitivity analyses will be conducted using lipid levels at three and twelve months after starting statin therapy. Conclusion Results will inform clinicians about the benefits of achieving guideline recommended concentrations of LDL-C for primary prevention of CVD.