Cardiovascular risks of nonsteroidal antiinflammatory drugs in patients after hospitalization for serious coronary heart disease.
BACKGROUND
The cardiovascular safety of individual nonsteroidal antiinflammatory drugs (NSAIDs) is highly controversial, particularly in persons with serious coronary heart disease.


RESULTS
We conducted a multisite retrospective cohort study of commonly used individual NSAIDs in Tennessee Medicaid, Saskatchewan Health, and United Kingdom General Practice Research databases. The cohort included 48566 patients recently hospitalized for myocardial infarction, revascularization, or unstable angina pectoris with more than 111000 person-years of follow-up. Naproxen users had the lowest adjusted rates of serious coronary heart disease (myocardial infarction, coronary heart disease death) and serious cardiovascular disease (myocardial infarction, stroke)/death from any cause, with respective incidence rate ratios (relative to NSAID nonusers) of 0.88 (95% CI, 0.66 to 1.17) and 0.91 (0.78 to 1.06). Risk did not increase with doses >or=1000 mg. Relative to NSAID nonusers, serious coronary heart disease risk increased with short term (<90 days) use for ibuprofen (1.67 [1.09 to 2.57]), diclofenac (1.86 [1.18 to 2.92]), celecoxib (1.37 [0.96 to 1.94]), and rofecoxib (1.46 [1.03 to 2.07]), but not for naproxen (0.88 [0.50 to 1.55]). Relative to naproxen, current users of diclofenac had increased risk of serious coronary heart disease (1.44 [0.96 to 2.15], P=0.076) and serious cardiovascular disease/death (1.52 [1.22 to 1.89], P=0.0002), and those of ibuprofen had increased risk of the latter end point (1.25 [1.02 to 1.53], P=0.032). Compared to naproxen in doses >or=1000 mg, serious coronary heart disease incidence rate ratios were increased for rofecoxib >25 mg (2.29 [1.24 to 4.22], P=0.008) and celecoxib >200 mg (1.61 [1.01 to 2.57], P=0.046).


CONCLUSIONS
In patients recently hospitalized for serious coronary heart disease, naproxen had better cardiovascular safety than did diclofenac, ibuprofen, and higher doses of celecoxib and rofecoxib.
Ray
Wayne A
WA
Department of Preventive Medicine, Division of Pharmacoepidemiology, Vanderbilt University School of Medicine, Nashville, TN, USA. wayne.ray@vanderbilt.edu
Varas-Lorenzo
Cristina
C
Chung
Cecilia P
CP
Castellsague
Jordi
J
Murray
Katherine T
KT
Stein
C Michael
CM
Daugherty
James R
JR
Arbogast
Patrick G
PG
García-Rodríguez
Luis A
LA
D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects*; D002318:Cardiovascular Diseases / Q000401:mortality*; D000068579:Celecoxib; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000401:mortality; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D004008:Diclofenac / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D006760:Hospitalization; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage / Q000009:adverse effects; D015994:Incidence; D007783:Lactones / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000401:mortality; D009288:Naproxen / Q000008:administration & dosage / Q000009:adverse effects*; D010045:Outpatients / Q000706:statistics & numerical data; D011720:Pyrazoles / Q000008:administration & dosage / Q000009:adverse effects; D012189:Retrospective Studies; D012307:Risk Factors; D020521:Stroke / Q000401:mortality; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects; D013450:Sulfones / Q000008:administration & dosage / Q000009:adverse effects; D013714:Tennessee / Q000453:epidemiology
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