Risk of nonfatal acute myocardial infarction associated with non-steroidal antiinflammatory drugs, non-narcotic analgesics and other drugs used in osteoarthritis: a nested case-control study

Pharmacoepidemiol Drug Saf. 2014 Nov;23(11):1128-38. doi: 10.1002/pds.3617. Epub 2014 Apr 1.

Abstract

Purpose: The purpose of this study is to estimate the risk of nonfatal acute myocardial infarction (AMI) associated with traditional NSAIDs (tNSAIDs), non-narcotic analgesics (paracetamol and metamizole), and symptomatic slow-acting drugs in osteoarthritis (SYSADOAs) overall and in different subgroups of patients.

Methods: We performed a nested case-control study using a Primary Care Database (Base de datos para la Investigación Farmacoepidemiológica en Atención Primaria), over the study period, 2001-2007. We included patients aged 40-90 years, with nonfatal AMI and randomly selected controls matched for age, sex and calendar year. Exposure to drugs was assessed within a 30-day window before the index date.

Results: We did not find an association with nonfatal AMI in patients at low-intermediate background cardiovascular risk (odds ratio = 0.92; 95% confidence interval: 0.76-1.12), whereas there was a moderate significant association among those at high risk (1.28; 1.06-1.54) or when tNSAIDs were used for longer than 365 days (1.43; 1.12-1.82). The greatest risk occurred when these two conditions were combined (1.80; 1.26-2.58). The risk varied across individual tNSAIDs, with ibuprofen (0.95; 0.78-1.16) in the lower and aceclofenac (1.59; 1.15-2.19) in the upper part of the range. Low-dose aspirin did not modify the risk profile showed by any of the individual tNSAIDs examined. Paracetamol (0.84; 0.74-0.95), metamizole (1.06; 0.87-1.29) and SYSADOAs (0.68; 0.47-0.99) were not associated with an increased risk overall or in any subgroup of patients.

Conclusions: The risk of nonfatal AMI varied with individual tNSAIDs, duration of treatment and background cardiovascular risk. Paracetamol, metamizole and SYSADOAs did not increase the risk in any of the conditions examined.

Keywords: NSAIDs; adverse drug reaction; analgesics; myocardial infarction; osteoarthritis; paracetamol; pharmacoepidemiology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Analgesics, Non-Narcotic / adverse effects*
  • Analgesics, Non-Narcotic / therapeutic use
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Cardiovascular Diseases / epidemiology
  • Case-Control Studies
  • Delayed-Action Preparations
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction / chemically induced*
  • Myocardial Infarction / epidemiology
  • Osteoarthritis / drug therapy*
  • Risk Factors

Substances

  • Analgesics, Non-Narcotic
  • Anti-Inflammatory Agents, Non-Steroidal
  • Delayed-Action Preparations