Patterns of LDL-C lowering by Statins and their association with Cardiovascular Outcomes in the General Population

Date of Approval: 
2016-12-08 00:00:00
Lay Summary: 
Since their introduction almost 30 years ago, statins remain the most successful class of drugs in the prevention of cardiovascular events through reducing low-density lipoprotein cholesterol (LDL-C, also known as "bad cholesterol"). In the United Kingdom, there are five types of statins available to patients at a range of doses and regimens; their effectiveness in reducing LDL-C as evaluated in clinical trials (published 1985 - 2003) informs current guidelines of their usage in patients at risk of cardiovascular events. Over time population change, generally for the better, for example, prevalence of smoking has continuously decreased since 1970 (HSCIC, 2016), therefore it is of interest to revisit past estimates of statin effectiveness in reducing LDL-C. We propose to use linked electronic health records to describe and examine usage and the effect this has on cardiovascular outcomes in a contemporary population. The primary benefit of the study will be to provide the most comprehensive resource of information on statin usage and we hope will help guide clinicians in the management of their patients.
Technical Summary: 
Objectives The main objective of this study is to determine the extent and impact of variation in statin treatment regimens on LDL-C and cardiovascular events on a national scale using linked electronic health records. Methods A retrospective longitudinal cohort study of statin usage and clinically relevant endpoints between 1997 and 2016 will be used to (1) match patients groups used in clinical trials to replicate statin dose-response characteristics; (2) extend this group to a more generalizable population at risk of CVD to understand how they are managed and respond in clinical practice. Data analysis Subjects will be selected based on their likeness to clinical trial participants at both individual and all trial levels. Statin persistence will be assessed through repeated prescriptions and LDL-C measurements. Comparative effectiveness between patient treatment strategies will be evaluated by identifying major pathways given patient indications and observance of the time-appropriate national guidelines.
Health Outcomes to be Measured: 
1. LDL-C plasma or serum 2. Cardiovascular events including death: - Hypertension - Stable angina - Unstable angina - Myocardial infarction - Cerebral haemorrhage - Haemorrhagic stroke - Ischaemic stroke - Heart failure - Peripheral aortic disease - Transient ischemic attack - Abdominal aortic aneurysm 3. All-cause mortality
Application Number: 

Folkert Asselbergs - Chief Investigator - University College London ( UCL )
Kenan Direk - Corresponding Applicant - University College London ( UCL )
Alireza Moayyeri - Collaborator - UCB Pharma SA - UK
Riyaz Patel - Collaborator - Barts Health and UCLH NHS Trusts
Rolf H.H. Groenwold - Collaborator - University Medical Centre Utrecht
Spiros Denaxas - Collaborator - University College London ( UCL )

HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation;Patient Level Townsend Score;Practice Level Index of Multiple Deprivation;MINAP;Other