The Gastrointestinal and Cardiovascular Safety of COX-2 selective inhibitors in general practice: the contribution of Prescription-Event Monitoring

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for many conditions, especially in the elderly. Whilst effective, they also have side-effects, most commonly on the stomach. Advances in the understanding of how NSAIDs work in the body led to newer NSAIDs (COX-2 selective inhibitors which are commonly known as 'coxibs') being developed with the potential for equivalent benefit to traditional NSAIDs but fewer side-effects because of how they affect enzymes involved in maintaining important body protective processes and inflammation. Rofecoxib (Vioxx) and celecoxib (Celebrex) were the first coxibs to become available. However, these claims of fewer side-effects may have led to selective prescribing ('channelling') of coxibs by doctors to patients who may be more susceptible to side-effects. Thus more side-effects have been seen during use than expected and recent scientific studies suggest that increases in cardiovascular side-effects as well as on the stomach are important. It is difficult to establish whether these increases are related to how these drugs work, or because of channelling. Although clinical trials are carried out prior to marketing, the numbers of people involved is limited (approximately 4000), thus the complete safety profile of a new drug is unknown prior to marketing. Therefore postmarketing studies are necessary to describe and quantify the use and safety of new drugs in various populations, as well as identify characteristics of patients at risk and other factors such as doctor preferences. In the UK, Prescription-Event Monitoring (PEM) is one such system which studies the safety of a new drug immediately it has been launched in large cohorts of patients (typically 10 000) under real-life conditions. It provides a valuable contribution in revealing patterns in prescribing and safety in daily general practice. The aim of this thesis was to add to what is known about the use and safety of coxibs in general practice, with data from postmarketing studies conducted in two European populations (English and Dutch). The studies of this thesis describe data obtained from the PEM database in the UK and the Stichting Farmaceutische Kengetallen (SFK) pharmaceutical claims database in the Netherlands.