Cardiovascular events associated with the use of four nonselective NSAIDs (etodolac, nabumetone, ibuprofen, or naproxen) versus a cyclooxygenase-2 inhibitor (celecoxib): a population-based analysis in Taiwanese adults.
BACKGROUND
Serious cardiovascular events (CVEs) have been linked to the use of cyclooxygenase (COX)-2 inhibitors, a category of selective NSAIDs. However, few studies are available that have compared the risk for CVEs between COX-2 inhibitors and nonselective NSAIDs in adults undergoing long-term treatment.


OBJECTIVE
The present study assessed (1) whether long-term use of nonselective NSAIDs (etodolac, nabumetone, ibuprofen, or naproxen) is associated with an increased risk for treatment-related CVEs (acute myocardial infarction [AMI], angina, cerebrovascular attack [CVA], and/or transient ischemic attack [TIA]) compared with long-term use of celecoxib and (2) which factors are associated with the risk for treatment-related CVEs in long-term users of nonselective NSAIDs in Taiwan.


METHODS
This population-based analysis used data from the Taiwanese Bureau of National Health Insurance (Taipei, Taiwan) database. Eligible patients were aged > or = 18 years and had been receiving etodolac, nabumetone, ibuprofen, naproxen, or celecoxib for > or = 180 days between January 1, 2001, and December 31, 2003. The primary outcomes measure was the prevalence of serious CVEs (AMI, angina, CVA, and/or TIA requiring hospitalization) after initiation of treatment. Analyses were performed on data from all eligible patients; person-time exposures to the drugs and hazard ratios (HRs) were calculated to determine the risk for CVEs with long-term use.


RESULTS
A total of 16,326 patients (8166 men, 8160 women; mean [SD] age, 61.83 [20.23] years) who had received long-term treatment with etodolac (2014 [12.34%]), nabumetone (2262 [13.86%]), ibuprofen (5239 [32.09%]), naproxen (3049 [18.68%]), or celecoxib (3762 [23.04%]) were identified. The overall prevalences of AMI, angina, CVA, and TIA were higher in long-term users with a history of cardiovascular disease (CVD) than in those without (AMI, 4.76% vs 0.99%; angina, 4.11% vs 0.43%; CVA, 7.74% vs 1.51%; and TIA, 4.03% vs 0.52%) (all, P < 0.01). The HRs for AMI, angina, CVA, and TIA were not significantly different between the NSAID and celecoxib groups. History of CVD played a significant role in recurrence during the period studied; the HRs (95% CIs) were 2.29 (1.22-4.32) for AMI, 6.19 (3.56-10.78) for angina, 3.56 (2.80-4.52) for CVA, and 6.60 (3.72-11.73) for TIA. Preexisting medical conditions (hypertension, dyslipidemia, diabetes mellitus, congestive heart failure, chronic renal disease) also significantly affected the risk for CVEs.


CONCLUSIONS
In this cohort study of long-term (> or = 180 days) use of NSAIDs in Taiwanese adults, no significant differences in the risk for treatment-related CVEs were observed between groups prescribed 1 of 4 nonselective NSAIDs (etodolac, nabumetone, ibuprofen, or naproxen) or celecoxib. History of CVD was the most significant determinant of CVE risk. Patients with preexisting medical conditions appeared to have a significantly higher risk for CVEs associated with the use of NSAIDs and celecoxib compared with patients without these conditions.
Huang
Weng-Foung
WF
Institute of Health and Welfare Policy, National Yang-Ming University, Taipei, Taiwan. huang@ym.edu.tw
Hsiao
Fei-Yuan
FY
Wen
Yu-Wen
YW
Tsai
Yi-Wen
YW
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects*; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000453:epidemiology; D000068579:Celecoxib; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D011720:Pyrazoles / Q000008:administration & dosage / Q000009:adverse effects*; D012189:Retrospective Studies; D012307:Risk Factors; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects*; D013624:Taiwan; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib