Comparison of Frequency and Outcome of Major Gastrointestinal Hemorrhage in Patients With Atrial Fibrillation on Versus Not Receiving Warfarin Therapy (from the ATRIA and ATRIA-CVRN Cohorts)

• Gastrointestinal hemorrhages on warfarin may be less life threatening than those occurring off warfarin.
• These findings are in stark contrast to the deleterious effect of warfarin on mortality from intracranial hemorrhage.
• These findings add to the positive net clinical benefit of warfarin therapy for most subgroups of patients with atrial fibrillation.

To date, there have been few studies evaluating outcomes of patients with atrial fibrillation (AF) who have experienced gastrointestinal (GI) hemorrhages. We examined short- and long-term mortality of major GI hemorrhage in patients with AF on and off warfarin in recent clinical care. We evaluated this association in the large Anticoagulation and Risk Factors in Atrial fibrillation (ATRIA) and ATRIA-Cardiovascular Research Network (CVRN) California community-based cohorts of patients with AF (study years 1996 to 2003 and 2006 to 2009, respectively), where all events were clinician adjudicated. We used proportional hazards regression with propensity score adjustment to estimate the short- (30 days) and long-term (>30 days for 1 year) mortality rate ratio for patients using warfarin compared with those who were not using warfarin at the time of GI hemorrhage. In the 414 ATRIA participants with major GI hemorrhage, 54% were taking warfarin at the time of the hemorrhage; in the 361 ATRIA-CVRN participants with major GI hemorrhage, 58% were taking warfarin. Warfarin use at the time of GI hemorrhage was not associated with 30-day mortality in the ATRIA cohort but was associated with significantly reduced 30-day mortality in the ATRIA-CVRN cohort (adjusted mortality rate ratio [95% confidence interval], ATRIA 0.97 [0.54 to 1.74]; ATRIA-CVRN 0.38 [0.17 to 0.83]). There was a modest suggestion of lower mortality on warfarin after 30 days in both cohorts. In conclusion, our study demonstrates that GI hemorrhages on warfarin are certainly no worse and may be less life threatening than those occurring off warfarin. These findings are in stark contrast to the deleterious effect of warfarin on mortality from intracranial hemorrhage and add another factor favoring anticoagulation in clinical decision making for patients with AF.