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

Joseph E Blais,Wallis Cy Lau,Esther W Chan,Kenneth Kc Man,Kebede A Beyene,Ralph Kwame Akyea,Annelize Coetzee,Jeff Harrison,Ian Ck Wong,Amy Hy Chan,Stephen Weng

doi:10.3399/bjgpopen20x101127

Abstract

BackgroundClinical 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). Furthermore, individual variability in lipid response to statin therapy requires assessment of the association in diverse populations.AimTo 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.Design & settingAn international, new-user, cohort study will be undertaken. It will use data from three electronic health record databases from three global regions: Clinical Practice Research Datalink, UK; PREDICT-CVD, New Zealand (NZ); and the Clinical Data and Analysis Reporting System, Hong Kong (HK).MethodNew 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, 1.4–1.7, 1.8–2.5, and ≥2.6 mmol/l) and non-HDL-C (<2.2, 2.2–2.5, 2.6–3.3, and ≥3.4 mmol/l) concentrations 24 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 3 and 12 months after starting statin therapy.ConclusionResults will inform clinicians about the benefits of achieving guideline recommended concentrations of LDL-C for primary prevention of CVD.

Highlights

cardiovascular disease (CVD) is the leading cause of death globally.[1]
Patients will be classified according to LDL-C (
To the authors’ knowledge, this is the first international study to assess LDL-C concentrations after initiating statin therapy for primary prevention of CVD in real-world populations. This extends the evidence obtained from randomised clinical trials

Summary

Introduction

CVD is the leading cause of death globally.[1]. Atherogenic lipoproteins (LDL-C and non-HDL-C) are well-established risk factors for atherosclerotic CVD.[2,3] Recent evidence from secondary prevention trials indicates that individuals with lower LDL-C concentrations have a reduced risk of subsequent cardiovascular events.[4,5]While lower targets for LDL-C are gaining wider acceptance for secondary prevention of CVD, there remains limited evidence for specific lipid targets for primary prevention. The recent European clinical guidelines for the treatment of dyslipidaemia emphasise specific LDL-C and non-HDL-C targets for primary prevention according to level of CVD risk.[6] whether achieving a specific lipid target while taking statin therapy for primary prevention corresponds to a reduction in cardiovascular events is uncertain, as most randomised controlled trials of statin therapy have not allocated patients to specific lipid targets. It is unknown whether there is a lipid level threshold, below which no added clinical benefit is obtained, and if a 'lower is better' approach is appropriate for primary prevention of CVD. Individual variability in lipid response to statin therapy requires assessment of the association in diverse populations

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