Nonvitamin K Anticoagulants: Risk of Bleeding When Interacting With Other Medications: A Cohort Study From Medicare

Clin Cardiol. 2024 Oct;47(10):e70023. doi: 10.1002/clc.70023.

Abstract

Introduction: Patients on nonvitamin K antagonist (NVKA) are usually taking other drugs. Potential interaction may increase the gastrointestinal (GI) bleeding risk associated with NVKA.

Methods: Observational cohort study using Medicare data from 2017 to 2020. Participants receiving a NVKA were included. A concomitant overlapping period while on NVKA was assessed for nonsteroidal anti-inflammatory drugs (NSAIDS), selective serotonin reuptake inhibitors (SSRI), antiplatelets, glucocorticoids, aspirin and proton pump inhibitors (PPI). A logistic regression predicting either any bleeding or GI bleeding was conducted estimating the odds ratio (OR) and 95% confidence interval (CI).

Results: A total of 102 531 people on NVKA with mean age 77 years (SD = 9.8) and 55% females (N = 56 671) were included. Previous history of GI bleeding occurred in 2 908 (2.8%) participants, concomitant exposure to PPI occurred in 38 713 (38%), SSRI in 16 487 (16%), clopidogrel in 15 795 (15.4%), NSAIDs in 13 715 (13.4%) and glucocorticoids in 13 715 (13.4%). Risk for any bleeding was shown for clopidogrel (OR: 1.37, 95% CI: 1.30, 1.44), prasugrel/ticagrelor (OR: 1.36, 95% CI: 1.18, 1.58), glucocorticoids (OR: 1.26, 95% CI: 1.19, 1.34), and SSRIs (OR: 1.13, 95% CI: 1.07, 1.19). GI bleeding risk was shown for clopidogrel (OR: 1.44, 95% CI: 1.34, 1.55), prasugrel/ticagrelor (OR: 1.47, 95% CI: 1.20, 1.79), SSRIs (OR: 1.09, 95% CI: 1.01, 1.17) and glucocorticoids (OR: 1.33, 95% CI: 1.23, 1.44). PPI use was correlated with both NSAID (r = 0.07, p ≤ 0.0001) and SSRI use (r = 0.09, p ≤ 0.0001).

Conclusion: NVKA concomitantly taken with antiplatelets, glucocorticoids, and SSRIs showed an increased risk for any bleeding and GI bleeding.

Keywords: drug interactions; factor Xa inhibitors; gastrointestinal hemorrhage; hemorrhage; risk factors.

Publication types

  • Observational Study
  • Multicenter Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anticoagulants* / adverse effects
  • Drug Interactions*
  • Female
  • Gastrointestinal Hemorrhage* / chemically induced
  • Gastrointestinal Hemorrhage* / epidemiology
  • Humans
  • Incidence
  • Male
  • Medicare*
  • Platelet Aggregation Inhibitors / adverse effects
  • Proton Pump Inhibitors / adverse effects
  • Retrospective Studies
  • Risk Assessment / methods
  • Risk Factors
  • Selective Serotonin Reuptake Inhibitors / adverse effects
  • United States / epidemiology

Substances

  • Anticoagulants
  • Proton Pump Inhibitors
  • Platelet Aggregation Inhibitors
  • Selective Serotonin Reuptake Inhibitors