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Association of non-steroidal anti-inflammatory drugs with outcomes in patients with ST-segment elevation myocardial infarction treated with fibrinolytic therapy: an ExTRACT-TIMI 25 analysis

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Abstract

Background Non-steroidal anti-inflammatory drugs (NSAIDs) may be prothrombotic, may worsen hypertension or congestive heart failure and obstruct access to the binding site of aspirin to cyclooxygenase-1 and thereby interfere with aspirin’s mechanism of action in reducing death and recurrent myocardial infarction (MI). We hypothesized that treatment with NSAIDs prior to an index MI would be associated with an increase in the risk of death, heart failure and recurrent MI among patients with ST-segment elevation MI (STEMI) treated with fibrinolytic therapy. Methods In ExTRACT-TIMI 25, patients with STEMI were treated with aspirin and fibrinolytic therapy and randomized to either enoxaparin or unfractionated heparin. We included patients who had received NSAIDs within 7 days of enrollment and evaluated the incidence of MI, the composite of death and MI and the composite of death, MI, severe heart failure and shock through 30 days. Results Of 20,479 patients enrolled, 572 (2.8%) received an NSAID within 7 days of enrollment. NSAID treatment prior to entry was associated with a higher incidence of 30-day death or nonfatal recurrent MI (15.9% vs. 10.8%, univariate P < 0.001). In multivariable models adjusting for randomization group and differences in baseline characteristics, NSAID use was associated with higher odds of MI (adjusted odds ratio [ORadj] 1.44, 95% confidence interval [CI] 1.01–2.07, P = 0.047), the composite of death and MI (ORadj 1.29, 95% CI 1.00–1.66, P = 0.051), and the composite of death, MI, severe heart failure and shock (ORadj 1.29, 95% CI 1.02–1.65, P = 0.037). Conclusions Among STEMI patients treated with a fibrinolytic agent and aspirin, use of NSAIDs in the week preceding the incident event was associated with a higher incidence of MI, the composite of death and MI as well as the composite of death, MI, severe heart failure and shock at 30 days.

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Acknowledgment

The ExTRACT-TIMI 25 study was supported in part by a grant from Sanofi-Aventis Pharma, Antony, France.

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Authors and Affiliations

  1. TIMI Study Group, Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 350 Longwood Avenue, First Floor, Boston, MA, 02115, USA

    C. Michael Gibson, Vijayalakshmi Kunadian, Cafer Zorkun, Jacqueline L. Buros & Sabina A. Murphy

  2. Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

    Yuri B. Pride

  3. Flinders Medical Centre, Adelaid, Australia

    Philip E. Aylward

  4. Clinique Universitaire St. Luc, Service de Cardiologie, Bruxelles, Belgium

    Jacques J. Col

  5. Terrence Donnelly Heart Centre, Division of Cardiology, St. Michael’s Hospital, University of Toronto, Toronto, ON, Canada

    Shaun G. Goodman

  6. Canadian Heart Research Centre, Toronto, ON, Canada

    Shaun G. Goodman

  7. Klinikum Rudolph-Virchow, Stockheim, Germany

    Dietrich Gulba

  8. Department of Cardiology, University Hospital Dubrava, Zagreb, Croatia

    Mijo Bergovec

  9. TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Elliott M. Antman

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  1. C. Michael Gibson
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Correspondence to C. Michael Gibson.

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Michael Gibson, C., Pride, Y.B., Aylward, P.E. et al. Association of non-steroidal anti-inflammatory drugs with outcomes in patients with ST-segment elevation myocardial infarction treated with fibrinolytic therapy: an ExTRACT-TIMI 25 analysis. J Thromb Thrombolysis 27, 11–17 (2009). https://doi.org/10.1007/s11239-008-0264-4

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  • DOI: https://doi.org/10.1007/s11239-008-0264-4

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