Prevalence, prediction, and health outcomes of cardioprotective medication reduction in the older UK population

Date of Approval
Application Number
Technical Summary

Accumulation of multiple long-term prescription drugs has led to so called polypharmacy, which can be specified as appropriate polypharmacy and problematic polypharmacy. Problematic polypharmacy, when multiple medications prescribed inappropriately or where the intended benefit of therapy is not met, is a risk factor to develop therapeutic related harm. This is particularly important for older individuals prescribed medications for cardiovascular disease prevention, where physiological changes and frailty may make them more susceptible to adverse drug reactions. Current guidelines therefore advise using clinical judgement when prescribing in older patients, and in some circumstances, consider reducing (stopping) medications which may cause harm. However, evidence to support this is currently lacking.

This study will examine the extent to which cardioprotective medication reduction (antiplatelets, anticoagulants, lipid-lowering, and antihypertensives) occurs in routine primary care practice. Furthermore, we aim to assess which patient characteristics predict medication reduction and examine the long-term safety and efficacy of cardioprotective medication reduction.

Aim 1: Develop and validate algorithmic approach to determine first routine cardioprotective medication reduction

Aim 2: Derive predictors of cardioprotective medication reduction from population characteristics using a matched case-control design (outcome is first cardioprotective medication reduction) with conditional logistic regression. Predictors will include patient characteristics, disease and treatment status, and lab parameters.

Aim 3: Determine the long-term safety and efficacy of cardioprotective medication reduction in an UK primary care population. A matched cohort study will be used where patients will be matched based on GP practice level. The exposure is the first incidence of cardioprotective medication reduction. The primary outcome will be all-cause hospitalisation, secondary outcomes will include major adverse cardiovascular events and drug-specific adverse events. A cox proportional hazards model will be used in order to examine the relationship between medication reduction and outcomes.

Health Outcomes to be Measured

Primary outcome
All-cause emergency hospitalisation

Secondary outcome
All-cause mortality; Stroke; Myocardial infarction; Cognitive functioning; Acute kidney injury; Electrolyte abnormalities; Falls; Fractures; Hypotension; Syncope; Cardiovascular Mortality; Worsening Heart Failure; Haemorrhage; muscle disorders; liver dysfunction; gastrointestinal and intracerebral bleeding

Specific outcomes will be examined in relation to reduction of specific drug group; anticoagulants, antihypertensives, antihyperlipidemic, or antiplatelet


James Sheppard - Chief Investigator - University of Oxford
Rik van der Veen - Corresponding Applicant - University of Oxford
Constantinos Koshiaris - Collaborator - University of Oxford
Kamal Mahtani - Collaborator - University of Oxford
Richard Hobbs - Collaborator - University of Oxford
Richard McManus - Collaborator - University of Oxford


HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation