Simultaneous assessment of short-term gastrointestinal benefits and cardiovascular risks of selective cyclooxygenase 2 inhibitors and nonselective nonsteroidal antiinflammatory drugs: an instrumental variable analysis.
OBJECTIVE
To simultaneously assess the short-term reduction in risk of gastrointestinal (GI) complications and increase in risk of acute myocardial infarction (MI) by celecoxib compared with rofecoxib and several nonselective nonsteroidal antiinflammatory drugs (NSAIDs) using instrumental variable analysis.


METHODS
A population of 49,711 Medicare beneficiaries ages 65 years and older who initiated nonselective NSAID or selective cyclooxygenase 2 inhibitor therapy between January 1, 1999, and December 31, 2002, was identified. The increase in risk of GI complications and MI within 180 days after initiation of NSAID (rofecoxib, diclofenac, ibuprofen, and naproxen compared with celecoxib) therapy was assessed using instrumental variable analysis.


RESULTS
Compared with nonselective NSAIDs, celecoxib reduced the risk of GI complications by 1.4 per 100 users but increased the risk of MI by 0.3 per 100 users. Rofecoxib decreased GI complications by 1.1 per 100 users and increased the risk of MI by 0.3 per 100 users. Using celecoxib as the reference exposure showed an increase in the MI risk for rofecoxib (risk difference [RD] 1.40, 95% confidence interval [95% CI] -0.20, 3.01) and diclofenac (RD 6.07, 95% CI -0.02, 12.15). The RD for naproxen as well as its upper 95% CI was the lowest of all NSAIDs (RD -0.30, 95% CI -2.74, 2.14) and there was no significant difference in GI complication rates among all NSAIDs.


CONCLUSIONS
In this instrumental variable analysis, diclofenac and rofecoxib had the least favorable benefit-risk balance among NSAIDs in older adults.
Schneeweiss
Sebastian
S
Harvard Medical School, Division of Pharmacoepidemiology and Pharmacoeconomics, Boston, MA 021205, USA. schneeweiss@post.harvard.edu
Solomon
Daniel H
DH
Wang
Philip S
PS
Rassen
Jeremy
J
Brookhart
M Alan
MA
D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects*; D000068579:Celecoxib; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D004008:Diclofenac / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005767:Gastrointestinal Diseases / Q000453:epidemiology* / Q000517:prevention & control; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage / Q000009:adverse effects; D007783:Lactones / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000453:epidemiology* / Q000517:prevention & control; D009288:Naproxen / Q000008:administration & dosage / Q000009:adverse effects; D011720:Pyrazoles / Q000008:administration & dosage / Q000009:adverse effects*; D012216:Rheumatic Diseases / Q000188:drug therapy; D018570:Risk Assessment; D012307:Risk Factors; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects*; D013450:Sulfones / Q000008:administration & dosage / Q000009:adverse effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D007783:Lactones; D011720:Pyrazoles; D013449:Sulfonamides; D013450:Sulfones; C116926:rofecoxib; D004008:Diclofenac; D009288:Naproxen; D000068579:Celecoxib; D007052:Ibuprofen