Use of cyclo-oxygenase 2 inhibitors (COX-2) and prescription non-steroidal anti-inflammatory drugs (NSAIDS) in UK and USA populations. Implications for COX-2 cardiovascular profile

Pharmacoepidemiol Drug Saf. 2006 Dec;15(12):861-72. doi: 10.1002/pds.1343.


Background: COX-2 and NSAIDS differ in their gastrointestinal (GI) and cardiovascular (CV) toxicity from pharmacological, clinical and epidemiologic point of views.

Objective: Describe the patterns of use of NSAIDS and COX-2 in The Health Improvement Network (THIN) database in UK and the PharMetrics database in USA.

Methods: We examined the experience of 10 distinct cohorts of new users of diclofenac, naproxen, ibuprofen, piroxicam, other NSAIDS, meloxicam, celecoxib, etoricoxib, rofecoxib and valdecoxib. The study period was 1 January 1995 through 2004 (31 March in UK and 28 February in USA). We collected information on covariates including history of upper GI disease, CV disease, hepatic disease, dosage, concomitant medication, and visits to a rheumatologist.

Results: We identified 486 076 unique patient-drug pairs in UK and 1 533 239 in USA. In UK population 78 201 (16%) were COX-2 users and in PharMetrics 324 206 (21%) were COX-2 users. Diclofenac and ibuprofen (NSAIDS), and celecoxib and rofecoxib (COX-2) were the agents prescribed most frequently. The duration of therapy was longer among celecoxib and rofecoxib users than among other users. More COX-2 users than NSAIDS users received concomitant gastroprotective agents (GPA), corticosteroids and anti-platelet therapy, and had a history of thromboembolic events and hypertension. PharMetrics patients were prescribed higher doses of NSAIDS and COX-2. The use of any single agent for more than 90 days was uncommon, but more frequent in PharMetrics. Switching was uncommon and was generally to a NSAID.

Discussion: Our results confirm some previous findings from other authors such as the presence of both GI and CV channelling to COX-2 agents but refute others, such as the frequency of drug switching between these agents. The typical use of COX-2 agents in practice is for shorter duration, and at lower doses, than was employed in randomized clinical trials. This difference may help clarify the apparent discrepancy with respect to CV toxicity between the results from clinical trials, which showed a higher CV risk with these drugs, and non-experimental epidemiologic studies, which showed lower or no increase in risk.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Antihypertensive Agents / therapeutic use*
  • Chemical and Drug Induced Liver Injury / epidemiology
  • Clinical Trials as Topic
  • Cyclooxygenase 2 Inhibitors / administration & dosage
  • Cyclooxygenase 2 Inhibitors / adverse effects*
  • Data Interpretation, Statistical
  • Databases, Factual
  • Drug Utilization / statistics & numerical data
  • Female
  • Gastrointestinal Diseases / chemically induced
  • Gastrointestinal Diseases / epidemiology
  • Humans
  • Hypertension / chemically induced*
  • Hypertension / drug therapy
  • Hypertension / epidemiology*
  • Kidney Diseases / chemically induced
  • Kidney Diseases / epidemiology
  • Male
  • Middle Aged
  • Product Surveillance, Postmarketing
  • Thromboembolism / chemically induced
  • Thromboembolism / epidemiology
  • United Kingdom / epidemiology
  • United States / epidemiology


  • Anti-Inflammatory Agents, Non-Steroidal
  • Antihypertensive Agents
  • Cyclooxygenase 2 Inhibitors