Published online before print May 5, 2009, doi: 10.1161/CIRCOUTCOMES.108.805689
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Original Articles |
Cardiovascular Risks of Nonsteroidal Antiinflammatory Drugs in Patients After Hospitalization for Serious Coronary Heart Disease
From the Department of Preventive Medicine, Division of Pharmacoepidemiology (W.A.R., J.R.D.), Vanderbilt University School of Medicine; the Department of Medicine, Divisions of Rheumatology (C.C., C.M.S.), Cardiology (K.T.M.), and Clinical Pharmacology K.T.M., C.M.S.), and Department of Biostatistics (P.G.A.); and Geriatric Research, Education and Clinical Center (W.A.R.), Veterans’ Administration Tennessee Valley Health Care System, Nashville, Tenn; Research Triangle Institute Health Solutions (C.V.L., J.C.) and Centro Español de Investigación Farmacoepidemiológica (L.A.G.R.), Barcelona, Spain.
Correspondence to Wayne A. Ray, PhD, Department of Preventive Medicine, Village at Vanderbilt, Suite 2600, 1501 21st Ave South, Nashville, TN 37212. E-mail wayne.ray{at}vanderbilt.edu
Received July 9, 2008; accepted February 12, 2009.
Background— The cardiovascular safety of individual nonsteroidal antiinflammatory drugs (NSAIDs) is highly controversial, particularly in persons with serious coronary heart disease.
Methods and 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 
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 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.
Key Words: antiinflammatory agents, nonsteroidal • coxib • rofecoxib • celecoxib • naproxen • diclofenac • coronary disease • myocardial infarction
The online-only Data Supplement is available at http://circoutcomes.ahajournals.org/cgi/content/full/10.1161/CIRCOUTCOMES.108.805689/DC1.
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