Clinical Question

Do nonsteroidal anti-inflammatory drugs (NSAIDs) increase the risk of bleeding and cardiovascular (CV) events in adults receiving antithrombotic therapy after myocardial infarction (MI)?

Bottom Line

The use of concomitant NSAIDs in adults who receive antithrombotic therapy after MI increases the risk of serious bleeding complications and recurrent adverse CV events. This study found the highest risk among users of celecoxib (Celebrex) and diclofenac, and the lowest risk among users of ibuprofen and naproxen. The risk of bleeding significantly increased in as little as zero to three days after beginning NSAID treatment and persisted for at least 90 days. (Level of Evidence = 2b)

Synopsis

These investigators linked information obtained from multiple databases in Denmark on hospital admissions, causes of death, and drug prescriptions to assess the association of concomitant NSAID use with the risks of bleeding and CV events in patients receiving antithrombotic treatment after MI. During the study period, the only NSAID available over the counter in Denmark was ibuprofen, 200 mg. Study participants included adults 30 years or older admitted to the hospital with a first-time MI from 2002 to 2011 and who survived at least 30 days after discharge. Outcomes included bleeding episodes requiring hospital admission or causing death, gross bleeding from the respiratory or urinary tract, and anemia caused by bleeding, as well as the combined outcome of CV death, nonfatal recurrent MI, ischemic cerebrovascular event, or systemic arterial emboli.

A total of 61,971 patients (mean age of 67.7 years) met inclusion criteria; 20,931 (33.8%) filled at least one NSAID prescription after discharge. Incidence rates of bleeding were significantly increased in patients with concomitant NSAID treatment compared with those without (4.2 events vs. 2.2 events per 100 person-years, respectively). All types of NSAIDs were associated with an increased risk of bleeding, although celecoxib (hazard ratio [HR] = 2.59; 95% confidence interval [CI], 1.68 to 3.98) and diclofenac (HR = 3.09; 95% CI, 2.55 to 3.75) increased risk more than ibuprofen (HR = 1.65; 95% CI, 1.39 to 1.96) and naproxen (HR = 1.56; 95% CI, 0.84 to 2.90). The risk of bleeding significantly increased in as little as zero to three days after beginning NSAID treatment and persisted for at least 90 days. Similarly, concomitant NSAID treatment was significantly associated with an increased risk of adverse CV events compared with no use of NSAIDs, with the highest risk again being among users of celecoxib (HR = 1.46; 95% CI, 1.13 to 1.89) and diclofenac (HR = 1.65; 95% CI, 1.44 to 1.90) and lowest among those taking ibuprofen (HR = 1.42; 95% CI, 1.28 to 1.57) and naproxen (HR = 0.86; 95% CI, 0.52 to 1.36). A sensitivity analysis excluding patients with rheumatoid arthritis (which independently increases the risk of CV disease) did not change the results.

Study design: Cohort (prospective)

Funding source: Foundation

Setting: Inpatient (any location) with outpatient follow-up

Reference: Schjerning OlsenAMGislasonGHMcGettiganPet alAssociation of NSAID use with risk of bleeding and cardiovascular events in patients receiving antithrombotic therapy after myocardial infarction. JAMA2015; 313( 8): 805– 814.