Risk of bleeding amongst warfarin and direct oral anticoagulant users prescribed immediate antibiotics for respiratory tract infection: Cohort study

Pharmacoepidemiol Drug Saf. 2024 May;33(5):e5794. doi: 10.1002/pds.5794.

Abstract

Purpose: Incidence of bleeding amongst warfarin and direct oral anticoagulant (DOAC) users is greater following a respiratory tract infection (RTI). It is unclear whether immediate antibiotics modify this association. We estimated the risk of bleeding amongst warfarin and DOAC users with RTI by antibiotic treatment.

Methods: This retrospective cohort study used data from the Clinical Practice Research Datalink (CPRD) GOLD for adults in England prescribed warfarin or a DOAC, who sought primary care for an RTI between 1st January 2011 and 31st December 2019. Outcomes were major bleeding (hospital admission for intracranial or gastrointestinal bleeding), and non-major bleeding (hospital admission or General Practice consult for epistaxis, haemoptysis, or haematuria). Cox models derived hazard ratios (HRs) and 95% confidence intervals (CIs) for each outcome, adjusting for confounders using inverse probability of treatment weighting.

Results: Of 14 817 warfarin and DOAC users consulting for an RTI, 8768 (59%) were prescribed immediate antibiotics and 6049 (41%) were not. Approximately 49% were female, and median age was 76 years. Antibiotics were associated with reduced risk of major bleeding (adjusted HR 0.38, 95% CI 0.25 to 0.58). This was consistent across several sensitivity analyses. Antibiotics were also associated with a reduced risk of non-major bleeding (adjusted HR 0.78, 95% CI 0.61 to 0.99).

Conclusions: Immediate antibiotics were associated with reduced risk of bleeding amongst warfarin and DOAC users with an RTI. Further work is needed to understand mechanisms and confirm whether a lower threshold for antibiotic use for RTI in this population may be beneficial.

Keywords: antibiotic; anticoagulant; cohort studies; haemorrhage; infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents* / administration & dosage
  • Anti-Bacterial Agents* / adverse effects
  • Anti-Bacterial Agents* / therapeutic use
  • Anticoagulants* / administration & dosage
  • Anticoagulants* / adverse effects
  • Cohort Studies
  • England / epidemiology
  • Female
  • Hemorrhage* / chemically induced
  • Hemorrhage* / epidemiology
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Respiratory Tract Infections* / drug therapy
  • Respiratory Tract Infections* / epidemiology
  • Retrospective Studies
  • Warfarin* / administration & dosage
  • Warfarin* / adverse effects

Substances

  • Warfarin
  • Anti-Bacterial Agents
  • Anticoagulants