Diclofenac is a non-steroidal anti-inflammatory drug (NSAID) commonly used to relieve pain and inflammation in patients with painful inflammatory conditions such as arthritis. However, recent clinical trials showed that use of diclofenac may be associated with increased risk of cardiovascular disease. Hydroxyzine is an antihistamine used for anxiety disorders, skin conditions (such as itch, eczema or rash) and sleep disorders. Clinical and post-marketing data both suggest its use may be associated with irregular heart beat and consequential serious heart disease. The European Medicines Agency has introduced new measures relating to the use of these drugs, aiming to minimise cardiovascular risks. The main elements of these were that they should not be used in patients with a history of heart attack, heart failure, peripheral arterial disease and/or stroke, and should be used with caution in patients with high blood pressure, high cholesterol or diabetes mellitus. Restrictions were introduced relating to the dose, duration and age of patients taking these medicines. The aim of this study is to determine how these regulatory actions have impacted on the use of these drugs and management of patients in the UK.
A population-based longitudinal observational study will be conducted using data from the CPRD database to examine trends in the prescribing of these drugs. The study population will consist of all patients registered with the CPRD database during the study period and will be followed up until death, end of follow-up or end of registration. The main outcome being evaluated will be changes in prescribing patterns of diclofenac, hydroxyzine and other related medicines. We will plot trends in the proportions of patients prescribed these drugs over the study period among each clinical patient group of interest. These groups include patients with ischaemic heart disease, heart failure, peripheral arterial disease, stroke and those at high risk of cardiovascular disease (high blood pressure, high cholesterol or diabetes, smokers). Step change and time trends in prescribing will be analysed using interrupted time series regression or jointpoint regression analyses to determine whether statistically significant changes in prescribing were associated with regulatory interventions.
Time trends in prescribing, switching, discontinuation and initiation rates
Thomas MacDonald - Chief Investigator - University of Dundee
Rob Flynn - Corresponding Applicant - University of Dundee
Aradhna Kaushal - Collaborator - University College London ( UCL )
Daniel Morales - Collaborator - University of Dundee
Isla Mackenzie - Collaborator - University of Dundee
Li Wei - Collaborator - University College London ( UCL )
Marta Berglund - Collaborator - University College London ( UCL )
Steve Morant - Collaborator - University of Dundee