The trade-off between cardiovascular and gastrointestinal effects of rofecoxib.
BACKGROUND
The cyclooxygenase-2 (COX-2) inhibitor rofecoxib was registered in 1999. By 2000, the first reports were published indicating that the agent was possibly associated with an increased risk of myocardial infarction. Since then a surge of data supporting this association has become available. To interpret these data it is essential to ascertain the cardiovascular risk profile of users of rofecoxib relative to other non-steroidal anti-inflammatory drug (NSAID) recipients.


OBJECTIVE
To assess differences in cardiovascular risk between starters of rofecoxib versus starters of any other NSAID.


METHODS
Data sampled from a representative research network of Dutch general practitioners (GPs) in 2001.


METHODS
New users (starters) of rofecoxib were compared to starters of any other NSAID, unmatched and matched on age, gender, and indication nested in the cohort of the second Dutch National Survey of General Practice.


RESULTS
A total of 40.4% of patients starting on rofecoxib had cardiovascular co-morbidity. Patients starting on rofecoxib were twice more likely to have a history of gastrointestinal (GI) morbidity, compared to patients starting on other NSAIDs (OR(adj) = 2.09; 95%CI = 1.65-2.66). These patients were also more likely to have cardiovascular co-morbidity (OR = 1.90; 95%CI = 1.60-2.24) compared to recipients of rofecoxib with no GI co-morbidity. Cardiovascular morbidity was present at the time of rofecoxib exposure in over 61% of carriers of a composite risk profile including age 60 years or older, GI co-morbidity and diagnosis of rheumatoid arthritis and osteoarthritis.


CONCLUSIONS
In general, a typical recipient of an NSAID is aged and carrier of a serious cardiovascular risk profile. Selective prescribing of rofecoxib to provide claimed gastroprotection, indirectly and unintentionally resulted in prescribing rofecoxib in a population with high frequencies of cardiovascular morbidities.
Florentinus
Stefan R
SR
Department of Pharmacoepidemiology and Pharmacotherapy, Utrecht University, Faculty of Pharmaceutical Sciences, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht, The Netherlands.
Heerdink
Eibert R
ER
de Boer
Antonius
A
van Dijk
Liset
L
Leufkens
Hubert G M
HG
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use; D001168:Arthritis / Q000188:drug therapy / Q000453:epidemiology; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000453:epidemiology; D015897:Comorbidity; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D005194:Family Practice; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D007783:Lactones / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D012189:Retrospective Studies; D018570:Risk Assessment; D013450:Sulfones / Q000009:adverse effects* / Q000627:therapeutic use
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007783:Lactones; D008565:Membrane Proteins; D013450:Sulfones; C116926:rofecoxib; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases