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Risk of myocardial infarction in patients taking cyclo-oxygenase-2 inhibitors or conventional non-steroidal anti-inflammatory drugs: population based nested case-control analysis.
BMJ. 2005 Jun 11; 330(7504):1366.BMJ

Abstract

AIMS

To determine the comparative risk of myocardial infarction in patients taking cyclo-oxygenase-2 and other non-steroidal anti-inflammatory drugs (NSAIDs) in primary care between 2000 and 2004; to determine these risks in patients with and without pre-existing coronary heart disease and in those taking and not taking aspirin.

DESIGN

Nested case-control study.

SETTING

367 general practices contributing to the UK QRESEARCH database and spread throughout every strategic health authority and health board in England, Wales, and Scotland.

SUBJECTS

9218 cases with a first ever diagnosis of myocardial infarction during the four year study period; 86 349 controls matched for age, calendar year, sex, and practice.

OUTCOME MEASURES

Unadjusted and adjusted odds ratios with 95% confidence intervals for myocardial infarction associated with rofecoxib, celecoxib, naproxen, ibuprofen, diclofenac, and other selective and non-selective NSAIDS. Odds ratios were adjusted for smoking status, comorbidity, deprivation, and use of statins, aspirin, and antidepressants.

RESULTS

A significantly increased risk of myocardial infarction was associated with current use of rofecoxib (adjusted odds ratio 1.32, 95% confidence interval 1.09 to 1.61) compared with no use within the previous three years; with current use of diclofenac (1.55, 1.39 to 1.72); and with current use of ibuprofen (1.24, 1.11 to 1.39). Increased risks were associated with the other selective NSAIDs, with naproxen, and with non-selective NSAIDs; these risks were significant at < 0.05 rather than < 0.01 for current use but significant at < 0.01 in the tests for trend. No significant interactions occurred between any of the NSAIDs and either aspirin or coronary heart disease.

CONCLUSION

These results suggest an increased risk of myocardial infarction associated with current use of rofecoxib, diclofenac, and ibuprofen despite adjustment for many potential confounders. No evidence was found to support a reduction in risk of myocardial infarction associated with current use of naproxen. This is an observational study and may be subject to residual confounding that cannot be fully corrected for. However, enough concerns may exist to warrant a reconsideration of the cardiovascular safety of all NSAIDs.

Authors+Show Affiliations

Institution 13th floor, Tower Building, University Park, Nottingham NG2 7RD. Julia.hippisley-cox@nottingham.ac.ukNo affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15947398

Citation

Hippisley-Cox, Julia, and Carol Coupland. "Risk of Myocardial Infarction in Patients Taking Cyclo-oxygenase-2 Inhibitors or Conventional Non-steroidal Anti-inflammatory Drugs: Population Based Nested Case-control Analysis." BMJ (Clinical Research Ed.), vol. 330, no. 7504, 2005, p. 1366.
Hippisley-Cox J, Coupland C. Risk of myocardial infarction in patients taking cyclo-oxygenase-2 inhibitors or conventional non-steroidal anti-inflammatory drugs: population based nested case-control analysis. BMJ. 2005;330(7504):1366.
Hippisley-Cox, J., & Coupland, C. (2005). Risk of myocardial infarction in patients taking cyclo-oxygenase-2 inhibitors or conventional non-steroidal anti-inflammatory drugs: population based nested case-control analysis. BMJ (Clinical Research Ed.), 330(7504), 1366.
Hippisley-Cox J, Coupland C. Risk of Myocardial Infarction in Patients Taking Cyclo-oxygenase-2 Inhibitors or Conventional Non-steroidal Anti-inflammatory Drugs: Population Based Nested Case-control Analysis. BMJ. 2005 Jun 11;330(7504):1366. PubMed PMID: 15947398.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Risk of myocardial infarction in patients taking cyclo-oxygenase-2 inhibitors or conventional non-steroidal anti-inflammatory drugs: population based nested case-control analysis. AU - Hippisley-Cox,Julia, AU - Coupland,Carol, PY - 2005/6/11/pubmed PY - 2005/6/28/medline PY - 2005/6/11/entrez SP - 1366 EP - 1366 JF - BMJ (Clinical research ed.) JO - BMJ VL - 330 IS - 7504 N2 - AIMS: To determine the comparative risk of myocardial infarction in patients taking cyclo-oxygenase-2 and other non-steroidal anti-inflammatory drugs (NSAIDs) in primary care between 2000 and 2004; to determine these risks in patients with and without pre-existing coronary heart disease and in those taking and not taking aspirin. DESIGN: Nested case-control study. SETTING: 367 general practices contributing to the UK QRESEARCH database and spread throughout every strategic health authority and health board in England, Wales, and Scotland. SUBJECTS: 9218 cases with a first ever diagnosis of myocardial infarction during the four year study period; 86 349 controls matched for age, calendar year, sex, and practice. OUTCOME MEASURES: Unadjusted and adjusted odds ratios with 95% confidence intervals for myocardial infarction associated with rofecoxib, celecoxib, naproxen, ibuprofen, diclofenac, and other selective and non-selective NSAIDS. Odds ratios were adjusted for smoking status, comorbidity, deprivation, and use of statins, aspirin, and antidepressants. RESULTS: A significantly increased risk of myocardial infarction was associated with current use of rofecoxib (adjusted odds ratio 1.32, 95% confidence interval 1.09 to 1.61) compared with no use within the previous three years; with current use of diclofenac (1.55, 1.39 to 1.72); and with current use of ibuprofen (1.24, 1.11 to 1.39). Increased risks were associated with the other selective NSAIDs, with naproxen, and with non-selective NSAIDs; these risks were significant at < 0.05 rather than < 0.01 for current use but significant at < 0.01 in the tests for trend. No significant interactions occurred between any of the NSAIDs and either aspirin or coronary heart disease. CONCLUSION: These results suggest an increased risk of myocardial infarction associated with current use of rofecoxib, diclofenac, and ibuprofen despite adjustment for many potential confounders. No evidence was found to support a reduction in risk of myocardial infarction associated with current use of naproxen. This is an observational study and may be subject to residual confounding that cannot be fully corrected for. However, enough concerns may exist to warrant a reconsideration of the cardiovascular safety of all NSAIDs. SN - 1756-1833 UR - https://www.unboundmedicine.com/medline/citation/15947398/Risk_of_myocardial_infarction_in_patients_taking_cyclo_oxygenase_2_inhibitors_or_conventional_non_steroidal_anti_inflammatory_drugs:_population_based_nested_case_control_analysis_ L2 - https://www.bmj.com/lookup/pmidlookup?view=long&amp;pmid=15947398 DB - PRIME DP - Unbound Medicine ER -