Cardiovascular (CV) disease is the leading cause of death and disability. A major group of CV disease is named atherosclerotic cardiovascular disease (ASCVD) and includes heart or blood-vessels diseases such as heart attack or stroke. Recent guidelines provide recommendations on risk categorization (low, moderate, high, and very-high) based on non-modifiable factors such as age, history of ASCVD, or diabetes, and on modifiable factors such as treatment or lifestyle strategies aiming to reduce the risk of such cardiovascular events. However, despite the availability of such strategy, there are limited information on how these recommendations apply to the entire high-risk population (including high and very high-risk individuals without ASCVD), and those with ASCVD. Therefore, this study aims to close these knowledge gaps by analysing two study populations (high-risk population and established ASCVD population) representing usual clinical practice setting in the United Kingdom, using anonymized information routinely collected during general practice visits and hospital stays, and from death certificates. In those 2 populations, we will first assess the number of ASCVD events such as heart attack, stroke, and cardiovascular death, then we will assess which factors, for instance, age, sex, concomitant diabetes or hypertension, are associated with ASCVD events or death. Lastly, we will observe which treatments were prescribed over time and the associated level of fat molecule called low-density lipoprotein cholesterol.
This study is a longitudinal retrospective observational cohort study based on a population with high and very high-risk of atherosclerotic cardiovascular disease (ASCVD) events (per the 2019 European Society of Cardiology and European Atherosclerosis Society dyslipidaemia guidelines), determined from Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES) databases in the United Kingdom. In addition to information on patient demographics and clinical characteristics, CPRD database will be utilized for treatment patterns and laboratory measures including low-density lipoprotein cholesterol (LDL-C), and HES and Office for National Statistics (ONS) databases to follow-up the study outcomes. Primary and first secondary objectives will describe event rates over time via Kaplan-Meier analyses for the primary outcome (a composite of nonfatal myocardial infarction (MI), nonfatal ischemic stroke, and cardiovascular (CV) death) and for the secondary outcomes (nonfatal MI, nonfatal ischemic stroke, CV death, unstable angina hospitalization, and elective coronary revascularization as a composite outcome and separately, and all-cause mortality), respectively. Possible risk factors for the primary and secondary outcomes will be assessed via Cox proportional hazards models and will include patient demographics, clinical characteristics, laboratory measures, lifestyle, and medication characteristics. Summary statistics of these variables will be provided as part of the second secondary objective. To address the last secondary objective, proportion of patients on various therapies, proportion of patients within categories of achieved LDL-C, rates of treatment-related events including treatment initiation, intensification, discontinuation, and re-start, and LDL-C levels will be described. Analyses will be provided separately for 1) high-risk primary prevention population without ASCVD and 2) population with ASCVD, and further stratified by index event. The knowledge generated by this study will help informing indirectly clinical practices guidelines (whether treatments are appropriately prescribed in these populations) and public health policy (whether some clinical conditions should be emphasized for the prevention of CV events).
Primary outcomes will be defined as the composite of nonfatal myocardial infarction (MI), nonfatal ischemic stroke, and cardiovascular (CV) death.
Secondary outcomes will be defined as nonfatal MI, nonfatal ischemic stroke, CV death, unstable angina hospitalization, and elective coronary revascularization as a composite outcome and separately, and all-cause mortality.
Descriptive variables during the follow-up will be lipid lowering therapies (LLT) (including statins, ezetimibe, and PCSK9 inhibitors) and achieved low-density lipoprotein cholesterol (LDL-C) levels.
Pia Horvat - Chief Investigator - IQVIA Ltd ( UK )
Christopher Lee - Corresponding Applicant - IQVIA Ltd ( UK )
Alexandra Koumas - Collaborator - Axtria Inc. USA
Ankita Chauhan - Collaborator - Axtria Inc. USA
Anna Castelo Branco - Collaborator - IMS Health Sweden AB
Aurore Tricotel - Collaborator - IQVIA Operations France SAS
Christian Siegfried - Collaborator - Axtria Inc. USA
Christopher Lee - Collaborator - IQVIA Ltd ( UK )
Emil Vatov - Collaborator - IQVIA Solution Bulgaria EOOD
Gianluca Lucrezi - Collaborator - IQVIA AG (Switzerland)
Jessica Lundbom - Collaborator - IQVIA Ltd ( UK )
Louise Raiteri - Collaborator - IQVIA Ltd ( UK )
Nelly Ly - Collaborator - IQVIA Ltd ( UK )
Nicole Rutishauser - Collaborator - IQVIA II Technology Solutions Portugal, Unipessoal LDA
Oriane BRETIN - Collaborator - IQVIA Operations France SAS
Quratul Ann - Collaborator - IQVIA Ltd ( UK )
Sophia Rodopoulou - Collaborator - IQVIA Hellas Technology Solutions S.A.
Stavros Oikonomou - Collaborator - IQVIA Solution Bulgaria EOOD
Sushant Pal - Collaborator - Axtria India Pvt. Ltd.
Tarana Mehdikhanova - Collaborator - IQVIA Ltd ( UK )
Vanessa Marzola - Collaborator - IMS Health Sweden AB
Cecilia Lourdudoss - Collaborator - IMS Health Sweden AB
Gianluca Lucrezi - Collaborator - IQVIA
Jessica Lundbom - Collaborator - IQVIA Ltd ( UK )
Pia Horvat - Collaborator - IQVIA Ltd ( UK )
Sarah Jenner - Collaborator - IQVIA Ltd ( UK )
HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation