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J Am Coll Cardiol, 2004; 43:985-990, doi:10.1016/j.jacc.2003.08.064
© 2004 by the American College of Cardiology Foundation
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CLINICAL RESEARCH: ASPIRIN, NON-STEROIDAL ANTI-INFLAMMATORY, AND CAD

The effects of nonselective non-aspirin non-steroidal anti-inflammatory medications on the risk of nonfatal myocardial infarction and their interaction with aspirin

Stephen E. Kimmel, MD, MS, FACC*{dagger},*, Jesse A. Berlin, ScD*, Muredach Reilly, MB*{dagger}, Jane Jaskowiak, BSN, RN*, Lori Kishel, MS*, Jesse Chittams, MS* and Brian L. Strom, MD, MPH*

* Center for Clinical Epidemiology and Biostatistics and Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
{dagger} Cardiovascular Division, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA

Manuscript received April 16, 2003; revised manuscript received August 11, 2003, accepted August 19, 2003.

* Reprint requests and correspondence: Dr. Stephen E. Kimmel, University of Pennsylvania School of Medicine, 717 Blockley Hall, 423 Guardian Drive, Philadelphia, Pennsylvania 19104-6021, USA.
skimmel{at}cceb.med.upenn.edu

OBJECTIVES: This study was designed to determine if non-aspirin non-steroidal anti-inflammatory drugs (NANSAIDs) are associated with lower odds of myocardial infarction (MI) and if NANSAIDs, particularly ibuprofen, interfere with aspirin's cardioprotective effect.

BACKGROUND: The NANSAIDs may reduce the risk of MI but may also interfere with aspirin's cardioprotective effect.

METHODS: A case-control study was conducted, with cases of first, nonfatal MI identified prospectively and controls identified randomly from the community.

RESULTS: The use of NANSAIDs was associated with a significant reduction in MI among those not using aspirin (adjusted odds ratio [OR] 0.53; 95% confidence interval [CI]: 0.42 to 0.67). This was true for both ibuprofen (adjusted OR 0.52; 95% CI: 0.39 to 0.69) and naproxen (adjusted OR 0.48; 95% CI: 0.28 to 0.82). Although aspirin itself was associated with decreased odds of MI in those not also using NANSAIDs (adjusted OR relative to no aspirin use 0.79; 95% CI: 0.63 to 0.98), it was not associated with decreased odds of MI among those who were using NANSAIDs (OR 1.28; 95% CI: 0.85 to 1.94; p value for interaction = 0.026). The association of aspirin and reduced odds of MI diminished with increasing frequency of NANSAID use (test for interaction p = 0.006), particularly for ibuprofen (p = 0.018). Among frequent (4 times/week) NANSAID users, the OR for aspirin versus no aspirin was 2.04 (95% CI: 1.06 to 3.94). Users of prophylactic aspirin plus frequent ibuprofen had an OR relative to aspirin-only users of 2.03 (95% CI: 0.60 to 6.84).

CONCLUSIONS: In the absence of aspirin use, NANSAIDs are associated with reduced odds of MI. In those using aspirin, NANSAIDs do not provide additional protection. Additional study is needed to determine the clinical impact of using NANSAIDs along with aspirin for cardioprotection.

Abbreviations and Acronyms
  CI = confidence interval
  COX = cyclooxygenase
  MI = myocardial infarction
  NANSAID = non-aspirin non-steroidal anti-inflammatory drug
  OR = odds ratio




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