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Original Investigation
February 24, 2015

Association of NSAID Use With Risk of Bleeding and Cardiovascular Events in Patients Receiving Antithrombotic Therapy After Myocardial Infarction

Author Affiliations
  • 1Department of Cardiology, Copenhagen University Hospital Gentofte, Hellerup, Denmark
  • 2The National Institute of Public Health, University of Southern Denmark, Copenhagen
  • 3William Harvey Research Institute (WHRI) at Barts and the London School of Medicine and Dentistry, United Kingdom
  • 4Department of Cardiology, the Heart Centre, Copenhagen University Hospital Rigshospitalet, Denmark
  • 5Department of Health, Science and Technology, Aalborg University, Denmark
JAMA. 2015;313(8):805-814. doi:10.1001/jama.2015.0809

Importance  Antithrombotic treatment is indicated for use in patients after myocardial infarction (MI); however, concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs) could pose safety concerns.

Objective  To examine the risk of bleeding and cardiovascular events among patients with prior MI taking antithrombotic drugs and for whom NSAID therapy was then prescribed.

Design, Setting, and Participants  Using nationwide administrative registries in Denmark (2002-2011), we studied patients 30 years or older admitted with first-time MI and alive 30 days after discharge. Subsequent treatment with aspirin, clopidogrel, or oral anticoagulants and their combinations, as well as ongoing concomitant NSAID use, was determined.

Exposures  Use of NSAIDs with ongoing antithrombotic treatment after first-time MI.

Main Outcomes and Measures  Risk of bleeding (requiring hospitalization) or a composite cardiovascular outcome (cardiovascular death, nonfatal recurrent MI, and stroke) according to ongoing NSAID and antithrombotic therapy, calculated using adjusted time-dependent Cox regression models.

Results  We included 61 971 patients (mean age, 67.7 [SD, 13.6] years; 63% men); of these, 34% filled at least 1 NSAID prescription. The number of deaths during a median follow-up of 3.5 years was 18 105 (29.2%). A total of 5288 bleeding events (8.5%) and 18 568 cardiovascular events (30.0%) occurred. The crude incidence rates of bleeding (events per 100 person-years) were 4.2 (95% CI, 3.8-4.6) with concomitant NSAID treatment and 2.2 (95% CI, 2.1-2.3) without NSAID treatment, whereas the rates of cardiovascular events were 11.2 (95% CI, 10.5-11.9) and 8.3 (95% CI, 8.2-8.4). The multivariate-adjusted Cox regression analysis found increased risk of bleeding with NSAID treatment compared with no NSAID treatment (hazard ratio, 2.02 [95% CI, 1.81-2.26]), and the cardiovascular risk was also increased (hazard ratio, 1.40 [95% CI, 1.30-1.49]). An increased risk of bleeding and cardiovascular events was evident with concomitant use of NSAIDs, regardless of antithrombotic treatment, types of NSAIDs, or duration of use.

Conclusions and Relevance  Among patients receiving antithrombotic therapy after MI, the use of NSAIDs was associated with increased risk of bleeding and excess thrombotic events, even after short-term treatment. More research is needed to confirm these findings; however, physicians should exercise appropriate caution when prescribing NSAIDs for patients who have recently experienced MI.