 |
 |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||
5 April 2005 | Volume 142 Issue 7 | Pages 481-489
Background: Cyclooxygenase-2 (COX-2) selective inhibitors have been marketed since 1999 as safer alternatives to nonsteroidal anti-inflammatory drugs (NSAIDs). Debate about their cardiac safety has culminated in the recent withdrawal of rofecoxib. Additional studies are needed to better understand this risk and to determine whether this safety concern represents a class effect.
Objective: To assess the influence of various NSAIDs on the risk for a first myocardial infarction (MI).
Design: Population-based, retrospective cohort study analyzed using a time-matched, nested case–control approach.
Setting: Québec, Canada.
Participants: 113 927 elderly persons without previous MI and newly treated with an NSAID between 1 January 1999 and 30 June 2002.
Measurements: NSAID exposure and occurrence of MI assessed by using Québec's administrative health databases.
Results: Compared with no use of NSAIDs in the year preceding the event, current use of rofecoxib was associated with an increased risk for an acute MI (rate ratio [RR], 1.24 [95% CI, 1.05 to 1.46]) that was more pronounced at higher doses (RR, 1.73 [CI, 1.09 to 2.76]). The concomitant use of aspirin appears to decrease the risk associated with low-dose rofecoxib (RR, 1.00 [CI, 0.77 to 1.28]) but not with high-dose rofecoxib (RR, 2.36 [CI, 1.27 to 4.39]). No increased risks were observed with celecoxib (RR, 0.99 [CI, 0.85 to 1.16]) or the other NSAIDs.
Limitations: The study could not completely account for all potential confounders, including over-the-counter use of aspirin and ibuprofen.
Conclusions: These results provide evidence of an increased risk for acute MI in current users of rofecoxib among elderly persons with no history of MI. This risk appears greater at higher doses. Aspirin use mitigates the risk associated with low-dose but not high-dose rofecoxib. There was no evidence of an increased risk with the other NSAIDs.
Editors' Notes
Context
Contribution
Cautions
–The Editors
Author and Article Information
From McGill University Health Centre, McGill University, Montréal, Québec, Canada.
Disclaimer: This study is based on nonidentifiable data provided by several Québec Government agencies. The interpretation and conclusions contained herein do not necessarily represent those of the government of Québec or these agencies.
Grant Support: By a grant from the Canadian Institutes of Health Research (CIHR grant MOP62871). Dr. Brophy is a Physician-Scientist of the Fonds de la recherche en santé du Québec.
Potential Financial Conflicts of Interest: None disclosed.
Requests for Single Reprints: James Brophy, MD, PhD, Cardiology Division, Room M4.76, McGill University Health Centre, Royal Victoria Hospital, 687 Pine Avenue West, Montréal, Québec H3A 1A1, Canada; e-mail, james.brophy{at}mcgill.ca.
Current Author Addresses: Ms. Lévesque and Drs. Brophy and Zhang: McGill University Health Centre, Royal Victoria Hospital, 687 Pine Avenue West, Montréal, Québec H3A 1A1, Canada.
Author Contributions: Conception and design: L.E. Lévesque, J.M. Brophy.
Analysis and interpretation of the data: L.E. Lévesque, J.M. Brophy, B. Zhang.
Drafting of the article: L.E. Lévesque, J.M. Brophy.
Critical revision of the article for important intellectual content: L.E. Lévesque, J.M. Brophy.
Final approval of the article: L.E. Lévesque, J.M. Brophy.
Provision of study materials: J.M. Brophy.
Statistical expertise: L.E. Lévesque, J.M. Brophy, B. Zhang.
Obtaining of funding: J.M. Brophy.
Administrative, technical, or logistic support: L.E. Lévesque, J.M. Brophy.
Collection and assembly of data: L.E. Lévesque, J.M. Brophy. ARTICLE
The Risk for Myocardial Infarction with Cyclooxygenase-2 Inhibitors: A Population Study of Elderly Adults
Related articles in Annals:
This article has been cited by other articles:
|
|
 |
|
  S. D. Solomon, J. Wittes, P. V. Finn, R. Fowler, J. Viner, M. M. Bertagnolli, N. Arber, B. Levin, C. L. Meinert, B. Martin, et al. Cardiovascular Risk of Celecoxib in 6 Randomized Placebo-Controlled Trials: The Cross Trial Safety Analysis Circulation, April 22, 2008; 117(16): 2104 - 2113. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. H. Hennekens and S. Borzak Cyclooxygenase-2 Inhibitors and Most Traditional Nonsteroidal Anti-inflammatory Drugs Cause Similar Moderately Increased Risks of Cardiovascular Disease Journal of Cardiovascular Pharmacology and Therapeutics, March 1, 2008; 13(1): 41 - 50. [Abstract] [PDF]
|
|
|
|
 |
|
 G. P. Joshi, R. Gertler, and R. Fricker Cardiovascular Thromboembolic Adverse Effects Associated with Cyclooxygenase-2 Selective Inhibitors and Nonselective Antiinflammatory Drugs Anesth. Analg., December 1, 2007; 105(6): 1793 - 1804. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. P. Kellogg, T. D. Wiggin, D. D. Larkin, J. M. Hayes, M. J. Stevens, and R. Pop-Busui Protective Effects of Cyclooxygenase-2 Gene Inactivation Against Peripheral Nerve Dysfunction and Intraepidermal Nerve Fiber Loss in Experimental Diabetes Diabetes, December 1, 2007; 56(12): 2997 - 3005. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P A Scott, G H Kingsley, C M Smith, E H Choy, and D L Scott Non-steroidal anti-inflammatory drugs and myocardial infarctions: comparative systematic review of evidence from observational studies and randomised controlled trials Ann Rheum Dis, October 1, 2007; 66(10): 1296 - 1304. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Klein, M. Eltze, T. Grebe, A. Hatzelmann, and M. Komhoff Celecoxib dilates guinea-pig coronaries and rat aortic rings and amplifies NO/cGMP signaling by PDE5 inhibition Cardiovasc Res, July 15, 2007; 75(2): 390 - 397. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. S. Reuben, E. F. Ekman, and D. Charron Evaluating the Analgesic Efficacy of Administering Celecoxib as a Component of Multimodal Analgesia for Outpatient Anterior Cruciate Ligament Reconstruction Surgery Anesth. Analg., July 1, 2007; 105(1): 222 - 227. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C Waksman, A. Brody, and S. D Phillips Nonselective Nonsteroidal Antiinflammatory Drugs and Cardiovascular Risk: Are They Safe? Ann. Pharmacother., July 1, 2007; 41(7): 1163 - 1173. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. S. Reuben and A. Buvanendran Preventing the Development of Chronic Pain After Orthopaedic Surgery with Preventive Multimodal Analgesic Techniques J. Bone Joint Surg. Am., June 1, 2007; 89(6): 1343 - 1358. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Madhok, O. Wu, G. McKellar, and G. Singh Non-steroidal anti-inflammatory drugs--changes in prescribing may be warranted Rheumatology, December 1, 2006; 45(12): 1458 - 1460. [Full Text] [PDF]
|
|
|
|
 |
|
 V. Schneider, L. E. Levesque, B. Zhang, T. Hutchinson, and J. M. Brophy Association of Selective and Conventional Nonsteroidal Antiinflammatory Drugs with Acute Renal Failure: A Population-based, Nested Case-Control Analysis Am. J. Epidemiol., November 1, 2006; 164(9): 881 - 889. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. McGettigan and D. Henry Cardiovascular Risk and Inhibition of Cyclooxygenase: A Systematic Review of the Observational Studies of Selective and Nonselective Inhibitors of Cyclooxygenase 2 JAMA, October 4, 2006; 296(13): 1633 - 1644. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Chaiamnuay, J. J. Allison, and J. R. Curtis Risks versus benefits of cyclooxygenase-2-selective nonsteroidal antiinflammatory drugs. Am. J. Health Syst. Pharm., October 1, 2006; 63(19): 1837 - 1851. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. Cheng Use of Non-Aspirin Nonsteroidal Antiinflammatory Drugs and the Risk of Cardiovascular Events Ann. Pharmacother., October 1, 2006; 40(10): 1785 - 1796. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Helin-Salmivaara, A. Virtanen, R. Vesalainen, J. M. Gronroos, T. Klaukka, J. E. Idanpaan-Heikkila, and R. Huupponen NSAID use and the risk of hospitalization for first myocardial infarction in the general population: a nationwide case-control study from Finland Eur. Heart J., July 2, 2006; 27(14): 1657 - 1663. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Rahme, Y. Toubouti, and E. Hunsche Therapy switching and associated costs in elderly patients receiving COX-2 selective inhibitors or non-selective non-steroidal anti-inflammatory drugs in Quebec, Canada Rheumatology, July 1, 2006; 45(7): 903 - 910. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. H. Gislason, S. Jacobsen, J. N. Rasmussen, S. Rasmussen, P. Buch, J. Friberg, T. K. Schramm, S. Z. Abildstrom, L. Kober, M. Madsen, et al. Risk of Death or Reinfarction Associated With the Use of Selective Cyclooxygenase-2 Inhibitors and Nonselective Nonsteroidal Antiinflammatory Drugs After Acute Myocardial Infarction Circulation, June 27, 2006; 113(25): 2906 - 2913. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G.B. J. Mancini, M. Etminan, B. Zhang, L. E. Levesque, J. M. FitzGerald, and J. M. Brophy Reduction of Morbidity and Mortality by Statins, Angiotensin-Converting Enzyme Inhibitors, and Angiotensin Receptor Blockers in Patients With Chronic Obstructive Pulmonary Disease J. Am. Coll. Cardiol., June 20, 2006; 47(12): 2554 - 2560. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. W. Armstrong Balancing the cyclooxygenase portfolio. Can. Med. Assoc. J., May 23, 2006; 174(11): 1581 - 1582. [Full Text] [PDF]
|
|
|
|
|
|
L. E. Levesque, J. M. Brophy, and B. Zhang Time variations in the risk of myocardial infarction among elderly users of COX-2 inhibitors Can. Med. Assoc. J., May 23, 2006; 174(11): 1563 - 1569. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Andersohn, S. Suissa, and E. Garbe Use of First- and Second-Generation Cyclooxygenase-2-Selective Nonsteroidal Antiinflammatory Drugs and Risk of Acute Myocardial Infarction Circulation, April 25, 2006; 113(16): 1950 - 1957. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. T. Chan, J. E. Manson, C. M. Albert, C. U. Chae, K. M. Rexrode, G. C. Curhan, E. B. Rimm, W. C. Willett, and C. S. Fuchs Nonsteroidal Antiinflammatory Drugs, Acetaminophen, and the Risk of Cardiovascular Events Circulation, March 28, 2006; 113(12): 1578 - 1587. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. R. Pijak, I. Huzicka, and F. Gazdik The Risk for Myocardial Infarction with Cyclooxygenase-2 Inhibitors Ann Intern Med, October 18, 2005; 143(8): 616 - 617. [Full Text] [PDF]
|
|
|
|
|
|
K. Shinmura and R. Bolli The Risk for Myocardial Infarction with Cyclooxygenase-2 Inhibitors Ann Intern Med, October 18, 2005; 143(8): 617 - 617. [Full Text] [PDF]
|
|
|
|
|
|
J. A. Kim, Y. S. Choi, D. Yoon, and K. H. Cho The Risk for Myocardial Infarction with Cyclooxygenase-2 Inhibitors Ann Intern Med, October 18, 2005; 143(8): 615 - 616. [Full Text] [PDF]
|
|
|
|
|
|
M. R. Pijak, I. Huzicka, and F. Gazdik Coxibs and cardiovascular risk Can. Med. Assoc. J., October 11, 2005; 173(8): 852 - 852. [Full Text] [PDF]
|
|
|
|
 |
|
 E. Fosslien Cardiovascular Complications of Non-Steroidal Anti-Inflammatory Drugs Ann. Clin. Lab. Sci., October 1, 2005; 35(4): 347 - 385. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. F. Jones and I. Power Editorial I: Postoperative NSAIDs and COX-2 inhibitors: cardiovascular risks and benefits Br. J. Anaesth., September 1, 2005; 95(3): 281 - 284. [Full Text] [PDF]
|
|
|
|
|
|
E. M. Antman, D. DeMets, and J. Loscalzo Cyclooxygenase Inhibition and Cardiovascular Risk Circulation, August 2, 2005; 112(5): 759 - 770. [Full Text] [PDF]
|
|
|
|
|
|
S C. Jones Relative Thromboembolic Risks Associated with COX-2 Inhibitors Ann. Pharmacother., July 1, 2005; 39(7): 1249 - 1259. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Brophy, S. D. Solomon, J. Wittes, J. McMurray, the APC Study Cardiovascular Safety Committee and, B. M. Psaty, and C. D. Furberg Cardiovascular Risk Associated with Celecoxib N. Engl. J. Med., June 23, 2005; 352(25): 2648 - 2650. [Full Text] [PDF]
|
|
Read all Rapid Responses
Article
