Patients Exposed to Rofecoxib and Celecoxib Have Different Odds of Nonfatal Myocardial Infarction

  1. Stephen E. Kimmel, MD, MSCE;
  2. Jesse A. Berlin, ScD;
  3. Muredach Reilly, MB;
  4. Jane Jaskowiak, BSN, RN;
  5. Lori Kishel, MS;
  6. Jesse Chittams, MS; and
  7. Brian L. Strom, MD, MPH
  1. From the University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.

    Abstract

    Background: Studies have postulated that cyclooxygenase-2 (COX-2) selective inhibitors affect cardiovascular risk through various mechanisms. Some of these mechanisms could increase risk (for example, inhibition of prostacyclin production), and some could decrease risk (for example, inhibition of inflammation).

    Objective: To determine the effect of COX-2 inhibitors on risk for nonfatal myocardial infarction (MI).

    Design: Case–control study.

    Setting: 36 hospitals in a 5-county area.

    Participants: 1718 case-patients with a first, nonfatal MI admitted to these hospitals and 6800 controls randomly selected from the same counties.

    Measurements: Self-reported medication use assessed through telephone interviews.

    Results: The adjusted odds ratio for MI among celecoxib users, relative to persons who did not use nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs), was 0.43 (95% CI, 0.23 to 0.79) compared with 1.16 (CI, 0.70 to 1.93) among rofecoxib users. The use of rofecoxib was associated with a statistically significant higher odds of MI compared with the use of celecoxib (adjusted odds ratio for rofecoxib vs. celecoxib, 2.72 [CI, 1.24 to 5.95]; P = 0.01). Nonselective NSAIDs were associated with a reduced odds of nonfatal MI relative to nonusers. Comparisons of COX-2 inhibitors with nonselective NSAIDs were the following: rofecoxib versus naproxen (odds ratio, 3.39 [CI, 1.37 to 8.40]) and celecoxib versus ibuprofen or diclofenac (odds ratio, 0.77 [CI, 0.40 to 1.48]).

    Limitations: The possibility of recall bias and uncontrolled confounding in this observational study limit the ability to make definitive conclusions. The association of celecoxib with a lower odds of MI could have occurred by chance. Only about 50% of eligible participants completed telephone interviews.

    Conclusion: Celecoxib and rofecoxib were associated with different odds of MI. Cardiovascular effects among the COX-2 inhibitors seem different, but further studies, preferably randomized trials, are needed to fully understand the spectrum of effects of COX-2 inhibitors and potential differences among them.

    Article and Author Information

    • Acknowledgments: The authors thank Sandy Barile for editorial assistance, Max Herlim for programming assistance, and William H. Sauer, MD, for assistance with data coding.

    • Grant Support: By the National Institutes of Health (R01HL57312), Searle Pharmaceuticals, Inc. (now Pfizer, Inc.), and Merck & Co., Inc.

    • Potential Financial Conflicts of Interest: Consultancies: S.E. Kimmel (Pfizer Inc.); J.A. Berlin (Wyeth-Ayerst, Johnson and Johnson, and GlaxoSmithKline); B.L. Strom (Pfizer, Inc., Novartis, Whitehall Robins, Wyeth-Ayerst); Honoraria: M. Reilly (Merck Frosst Canada Ltd., GlaxoSmithKline); B.L. Strom (Abbott, Wyeth-Ayerst, Pfizer, Inc.); Expert testimony: B.L. Strom (Bayer, Parke-Davis, GlaxoSmithKline); Grants received: S.E. Kimmel (Pfizer, Inc., Merck & Co., Inc.); J.A. Berlin (McNeil, Pfizer, Inc., Merck & Co., Inc.); M. Reilly (Merck & Co., Inc., GlaxoSmithKline); B.L. Strom (Bayer, GlaxoSmithKline, Merck & Co., Inc., Pfizer, Inc., Wyeth-Ayerst, Pharmacia, Whitehall Robins).

    • Requests for Single Reprints: Stephen E. Kimmel, MD, MS, University of Pennsylvania School of Medicine, 717 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104-6021.

    • Current Author Addresses: Dr. Kimmel: University of Pennsylvania School of Medicine, 717 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104-6021.

    • Dr. Berlin: Research and Development, LLC, Johnson and Johnson Pharmaceutical, 1125 Trenton-Harbourton Road, Titusville, NJ 08560.

    • Dr. Reilly: Hospital University of Pennsylvania, 9 Founders, 3400 Spruce Street, Philadelphia, PA 19104.

    • Ms. Jaskowiak: University of Pennsylvania, 731 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104.

    • Ms. Kishel: 220 Locust Street, Apt 9F, Philadelphia, PA 19106.

    • Mr. Chittams: University of Pennsylvania, 525GH Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104.

    • Dr. Strom: University of Pennsylvania, 824 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104.

    • Author Contributions: Conception and design: S.E. Kimmel, J.A. Berlin, B.L. Strom.

    • Analysis and interpretation of the data: S.E. Kimmel, J.A. Berlin, M. Reilly, J. Jaskowiak, L. Kishel, J. Chittams.

    • Drafting of the article: S.E. Kimmel, J.A. Berlin, M. Reilly.

    • Critical revision of the article for important intellectual content: S.E. Kimmel, J.A. Berlin, M. Reilly, J. Jaskowiak, L. Kishel, B.L. Strom.

    • Final approval of the article: S.E. Kimmel, J.A. Berlin, M. Reilly, J. Jaskowiak, L. Kishel, J. Chittams, B.L. Strom.

    • Statistical expertise: J.A. Berlin, J. Chittams.

    • Obtaining of funding: S.E. Kimmel, J.A. Berlin.

    • Collection and assembly of data: J. Jaskowiak, L. Kishel.

    Responses to this article

    • Is Medicine based on evidences or merely on opinion? An example: cardiotoxicity of COX-2 inhibitors.
      • Salvatore Corrao
      Ann Intern Med published online October 26, 2009
    • COX-2 and Perceptions of Conflict of Interest
      • David A. Nardone
      Ann Intern Med published online October 26, 2009

    Summary for Patients

    • Summaries for Patients:Cyclooxygenase-2 Inhibitors and Heart Attacks: Varying Effects? Ann Intern Med February 1, 2005 142:I-21
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