Osteoarthritis (OA) is the commonest arthritis worldwide. It is strongly associated with ageing and is a leading cause of joint pain and disability. Pain is the commonest complaint that causes people with OA to see their doctors. Paracetamol is the first line painkiller that most doctors recommend for OA pain because it is thought to be safer than other painkillers. However, data from recent studies have shown that paracetamol can be harmful for gut, heart and kidney when used for long periods. This has questioned the widespread use of paracetamol for chronic painful conditions such as osteoarthritis (OA). This study aims to examine the safety of paracetamol. We will utilise the data from Clinical Practice Research Datalink to identify paracetamol users and non-users from UK primary healthcare records. We will then compare the number of side effects that develop in people prescribed paracetamol with those not prescribed paracetamol. We are particularly interested in the side effects affecting the gut, heart and kidney as well as overall death rate. We will balance the two comparative groups for other risk factors associated with these side effects such as age, gender and likelihood of being prescribed paracetamol.
Background
The recent NICE-guideline on OA (2014) suggests that benefits of paracetamol are comparatively low and the adverse effects it can cause in long-term usage are more common than were thought previously [1].
Aims
This research aims to analyse the association of paracetamol with gastrointestinal events (such as perforation, peptic ulcer, upper and lower gastrointestinal bleeding), cardiovascular events (hypertension, myocardial infarction, haemorrhagic and ischaemic stroke), chronic kidney disease and all-cause mortality with a long follow-up period of upto 20years using primary healthcare records.
Methods
The eligible people must be aged 65years or older, registered with the up-to-standard practices for at least 12months. The paracetamol users are defined as participants who receive at least two prescriptions of paracetamol from their GPs within 6months. The first prescription date will be the index date. We will match each user with non-user according age, gender and propensity-score. Non-users are the participants who do-not receive two paracetamol prescriptions within 6 months over the study period. The same index date will be assigned for user and the matched non-user.
Statistical analysis
The propensity score will be calculated using the logistic-regression model. The likelihood of receiving paracetamol will be the dependent variable and smoking, alcohol consumption, comorbidities and analgesic use will be independent variables. The follow-up will start 12months after the index-date (landmark-date to avoid miscounting any outcome prior to the qualification as a paracetamol-user). This will provide an exposure window between the index-date and landmark-date to accumulate number of prescriptions and doses for a dose-response analysis.
Participants will be followed-up until the first incidence of outcome of interest, deregistration from the practice, death or end of the study whichever comes first. Kaplan-Meier-curves will be used to estimate the cumulative probabilities of the outcomes. We will use cox-proportional hazard regression to calculate the hazard ratio.
Primary outcome: incidence rate of gastro-intestinal adverse events (namely perforation, peptic ulcer, upper/lower gastrointestinal bleeding separately and as a composite outcome) in the risk measure of per 1000 person-years.
Secondary outcomes: incident rate Cardiovascular events, incident rate chronic kidney disease and mortality
Weiya Zhang - Chief Investigator - University of Nottingham
Jaspreet Kaur - Corresponding Applicant - University of Nottingham
Abhishek Abhishek - Collaborator - University of Nottingham
Christian Mallen - Collaborator - Keele University
Georgina Nakafero - Collaborator - University of Nottingham
Michael Doherty - Collaborator - University of Nottingham
HES Admitted Patient Care;ONS Death Registration Data;Practice Level Index of Multiple Deprivation