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

Abstract

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.

Objectives:

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 ≥18 years and had been receiving etodolac, nabumetone, ibuprofen, naproxen, or celecoxib for ≥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 (≥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.