Subgroup analyses to determine cardiovascular risk associated with nonsteroidal antiinflammatory drugs and coxibs in specific patient groups.
OBJECTIVE
To explore the extent to which clinical characteristics influence the association between cyclooxygenase 2 inhibitors (coxibs) and/or nonselective nonsteroidal antiinflammatory drugs (NSAIDs) and increased cardiovascular disease (CVD) risk in specific patient subgroups. There is substantial concern regarding the potential cardiovascular adverse effects of selective coxibs and nonselective NSAIDs, but many patients with arthritis experience important clinical benefits from these agents.


METHODS
The study population consisted of Medicare beneficiaries also eligible for a drug benefits program for older adults during the years 1999-2004. We calculated the relative risk (RR) for CVD events (myocardial infarction [MI], stroke, congestive heart failure, and cardiovascular death) among users of coxibs or nonselective NSAIDs in the prior 6 months compared with nonusers. We assessed biologic interaction between these medication exposures and important patient characteristics.


RESULTS
In the primary cohort, we identified 76,082 new users of coxibs, 53,014 new users of nonselective NSAIDs, and 46,558 nonusers. Compared with nonusers, the adjusted RR of CVD events for new users of each agent increased for rofecoxib (RR 1.22, 95% confidence interval [95% CI] 1.14, 1.30) and decreased for naproxen (RR 0.79, 95% CI 0.67, 0.93). Several patient characteristics were found to increase the risk of CVD events among users of some agents in both the primary and secondary cohorts, including age >/=80 years, hypertension, prior MI, prior CVD, rheumatoid arthritis, chronic renal disease, and chronic obstructive pulmonary disease. Rofecoxib and ibuprofen appeared to confer an increased risk in multiple patient subgroups.


CONCLUSIONS
Many nonselective NSAIDs and coxibs are not associated with an increased risk of CVD events. However, several patient characteristics identify important subgroups that may be at an increased risk when using specific agents.
Solomon
Daniel H
DH
Brigham and Women's Hospital, 1620 Tremont Street, Boston, MA 02120, USA. dhsolomon@partners.org
Glynn
Robert J
RJ
Rothman
Kenneth J
KJ
Schneeweiss
Sebastian
S
Setoguchi
Soko
S
Mogun
Helen
H
Avorn
Jerry
J
Stürmer
Til
T
D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects*; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001168:Arthritis / Q000188:drug therapy* / Q000453:epidemiology*; D002318:Cardiovascular Diseases / Q000453:epidemiology*; D015331:Cohort Studies; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D016208:Databases, Factual / Q000706:statistics & numerical data; D005260:Female; D006333:Heart Failure / Q000453:epidemiology; D006801:Humans; D008297:Male; D009203:Myocardial Infarction / Q000453:epidemiology; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D018501:Antirheumatic Agents; D052246:Cyclooxygenase 2 Inhibitors