Nonsteroidal antiinflammatory drugs and the risk of myocardial infarction in the general population.
BACKGROUND
Nonsteroidal antiinflammatory drugs (NSAIDs) are reversible inhibitors of cyclooxygenase (COX)-1 and COX-2. Whether transient and incomplete COX-1 inhibition with NSAIDs other than aspirin will translate into clinical cardioprotection is unclear. Some reports suggest that concurrent aspirin and ibuprofen might be associated with lower cardioprotection than aspirin alone because of a pharmacodynamic interaction.


RESULTS
We conducted a cohort study with a nested case-control analysis. Overall, 4975 cases of acute myocardial infarction (MI) and death from coronary heart disease (CHD) were identified (January 1997 to December 2000) in the UK. A total of 20,000 controls were randomly sampled, and frequency was matched to cases by age, sex, and calendar year. The incidence rate was 5.0 per 1000 person-years. The multivariate-adjusted OR for current NSAID use compared with nonuse was 1.07 (95% CI, 0.95 to 1.20). Treatment duration or daily dose did not change the results. The effect was similar among patients free of CHD history (1.04; 95% CI, 0.90 to 1.20) and patients with previous history (1.12; 95% CI, 0.91 to 1.38). Estimates for individual NSAIDs were all comparable, with no major effect on the risk of acute MI. Naproxen was associated with an OR of 0.89 (95% CI, 0.64 to 1.24). The OR of aspirin and concurrent NSAIDs use was 1.10 (95% CI, 0.89 to 1.37) compared with aspirin alone. We observed the same result when analyzing ibuprofen and aspirin taken concomitantly.


CONCLUSIONS
This study could not demonstrate any detectable risk reduction of NSAIDs on the occurrence of MI. Our results do not support the existence of a clinically meaningful interaction between aspirin and NSAIDs, including ibuprofen.
García Rodríguez
Luis A
LA
Centro Español de Investigación Farmacoepidemiológica, Madrid, Spain. lagarcia@ceife.es
Varas-Lorenzo
Cristina
C
Maguire
Andrew
A
González-Pérez
Antonio
A
D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D016022:Case-Control Studies; D015331:Cohort Studies; D015897:Comorbidity; D003327:Coronary Disease / Q000188:drug therapy / Q000401:mortality; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D004008:Diclofenac / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004363:Drug Utilization; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D007783:Lactones / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000139:chemically induced / Q000453:epidemiology / Q000517:prevention & control*; D009288:Naproxen / Q000494:pharmacology / Q000627:therapeutic use; D016017:Odds Ratio; D012307:Risk Factors; D013030:Spain / Q000453:epidemiology; D013450:Sulfones
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002316:Cardiotonic Agents; D016861:Cyclooxygenase Inhibitors; D007783:Lactones; D013450:Sulfones; C116926:rofecoxib; D004008:Diclofenac; D009288:Naproxen; D001241:Aspirin; D007052:Ibuprofen