- Clarithromycin use in older patients taking direct oral anticoagulants (DOACs) increases risk for major hemorrhage requiring hospitalization vs using azithromycin.
Why this matters
- Clinicians should assess individual hemorrhage risk, anticoagulation needs, and antibiotic substitutes when co-prescribing DOACs and macrolides.
- In situations in which concomitant clarithromycin/DOACs are inevitable, monitor to prevent DOACs supratherapeutic levels.
- 24,943 patients; 36.2% (9025) ages 66-75 years.
- 26.4% received clarithromycin, 73.6% azithromycin.
- DOACs: rivaroxaban 40.0%, apixaban 31.9%, dabigatran 28.1%.
- Mean (standard deviation) duration of DOAC use before antibiotic administration: 390 days (0.11) before azithromycin vs 353 days (0.11) before clarithromycin.
- Incident hemorrhage rate (95% CI) was higher with clarithromycin vs azithromycin:
- 204.8 (191.3-219.7) vs 133.7 (127.0-140.8).
- In a self-controlled case series analysis, for periods of clarithromycin use (145 events) vs nonuse (1615 events), the rate ratio was 1.64 (95% CI, 1.35-1.98).
- 30-day major hemorrhage rate requiring hospital admission in patients taking clarithromycin vs azithromycin:
- Adjusted HR, 1.71 (95% CI, 1.20-2.45).
- Retrospective, population-based cohort evaluation of elevated bleeding risk among older patients age ≥66 years taking DOACs with concomitant clarithromycin vs azithromycin, June 23, 2009 to December 31, 2016.
- Funding: Heart and Stroke Foundation of Canada.
- Limited generalizability.
- Small number of bleeding events.
- Dosage adjustments adherence unaccounted for.
- Unmeasured confounding.