Life expectancy has increased in recent decades, driven by advances in medical sciences. Diseases which would drastically lower life expectancy previously are now successfully treated with multiple drugs. Older people tend to accumulate more life-long conditions and therefore take more prescription drugs. However, taking multiple drugs may not but without risk. Some can cause side effects which might be serious. These include drugs used to prevent heart disease, such as those used to lower blood pressure and cholesterol. One way to prevent possible harm could be to reduce the number of drugs prescribed in patients where the benefits of continued treatment may be outweighed by the harms. However, the harms and benefits of reducing these drugs in patients are currently unknown.
This proposal aims to use the information from the medical records from patients in the United Kingdom to establish which drugs used to prevent heart attacks and strokes are currently stopped in current routine practice. We will also examine what events preceded the decision to stop certain prescriptions, and what outcomes occurred after the prescription was stopped. We will focus on prescriptions that are used to prevent heart disease like those who treat high blood pressure, lower cholesterol, and blood thinners. Information gathered can be used to inform general practitioners who might benefit from stopping or reducing drugs used to prevent heart attack and stroke.
Background
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.
Aims
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.
Methods
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.
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
Anna Seeley - Collaborator - 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
Anna Seeley - Collaborator - 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