Statins, the most common cholesterol lowering treatments are recommended in national guidelines to prevent future heart disease and strokes. However, it is well-known that statins do not lower cholesterol in all patients. Many previous studies have suggested that there may be different patient characteristics which can influence how well cholesterol is lowered by statins in different patients.
As most statin treatments are started and monitored in primary care, there is a need to understand which patient characteristics may affect changes in cholesterol levels. This will lead to the development of a clinical tool to help doctors and nurses to better identify patients who are likely respond to statin therapy from those who do not respond well.
Using electronic patient records from general practices across the UK, this study aims to:
1. Identify important patient characteristics of lipid response to statins among patients.
2. Using these predictors, we will develop a clinical tool which can help doctors and nurses to better predict a patient's change in cholesterol when statins are started.
3. Determine long-term heart disease and stroke outcomes in patients who respond well to statins compared to those who not respond well.
Background: There is significant variability in cholesterol lowering and change in cardiovascular disease (CVD) risk when statins are initiated, but no method of predicting response to statin therapy.
Objectives: (1) To determine patient factors, routinely collected in primary care health records, associated with lipid response to statins (2) To derive and validate a clinical algorithm to predict lipid response to statins (3) To determine long term cardiovascular outcomes of patients stratified by lipid response.
Study Design: Cohort study using CRPD data and linked HES, patient-level IMD and ONS-mortality data
Setting: UK General Practice
Participants: Patients free from CVD at baseline, registered at their practice at least one year before study entry, being treated with statins, with at least 2 recorded cholesterol (LDL or TC) readings - the baseline measure being within 12 months before the initiation of statins and follow-up measure being within 24 months after intitiation of statins.
Outcomes: Primary: Change in (1) total cholesterol and (2) LDL cholesterol during 24 month follow-up after initiation of statins; Secondary: First occurence of cardiovascular disease after 24 months from initiation of statins.
Methods: The study population will be randomly split into algorithm derivation and validation cohorts (30% sample). To predict cholesterol response, a repeated measures model (mixed model) will be created. Models will be tested for predictive accuracy in the validation cohort. A time-to-event analysis will investigate relationships between lipid response, patient modifiable and non-modifiable clinical and demographic characteristics, and cardiovascular outcomes.
Primary Primary Outcomes:
- Change in total cholesterol over time (continuous)
- Change in LDL cholesterol over time (continuous)
Secondary Outcomes:
- Long term follow-up for development of cardiovascular disease (coronary heart disease, stroke, transient ischaemic attack and peripheral arterial disease)
Stephen Weng - Chief Investigator - University of Nottingham
Stephen Weng - Corresponding Applicant - University of Nottingham
Barbara Iyen - Collaborator - University of Nottingham
Joe Kai - Collaborator - University of Nottingham
Nadeem Qureshi - Collaborator - University of Nottingham
Ralph Kwame Akyea - Collaborator - University of Nottingham
HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation