A recent cohort study found differences in treatment and outcomes of major bleeding between patients taking warfarin and those taking direct oral anticoagulants (DOACs).

Patients had atrial fibrillation or flutter, were 66 years of age or older, and presented to one of five tertiary care hospitals in Ontario, Canada, with oral anticoagulant-related major bleeding (exposure to dabigatran, rivaroxaban, apixaban, or warfarin within three days of presentation). The primary outcome was treatment strategy during the course of the hospital encounter, and secondary outcomes were in-hospital and 30-day mortality. Researchers included 2,002 cases (460 DOAC and 1,542 warfarin) involving 1,799 patients in their analysis. Results were published online in February by Chest.

Among DOAC cases, 245 (53.3%) involved dabigatran, 155 (33.7%) involved rivaroxaban, and 60 (13.0%) involved apixaban. Patients were 81.2 years old on average, had a mean CHA2DS2-VASc score of 4.4, and had a median HAS-BLED score of 3.

Intracranial hemorrhages, especially subdural hematomas, comprised a higher proportion of major bleeding in patients taking warfarin compared to those taking DOACs (29.8% vs. 21.9%, P<0.001 for all intracranial bleeds). A higher proportion of gastrointestinal bleeding, especially in the lower gastrointestinal tract, was seen in the DOAC cohort (61.7% vs. 42.5%, P<0.001, for all gastrointestinal bleeds). Fewer DOAC patients required transfusion of blood products than those on warfarin (278 [60.4%] vs. 1,014 [65.8%]; adjusted risk ratio [RR], 0.92, 95% CI, 0.85 to 1.00). Reflecting the gastrointestinal-predominant bleeding pattern, packed red blood cells were most frequently used in DOAC-related events, whereas prothrombin complex concentrate, vitamin K, and fresh frozen plasma were used more in cases involving warfarin.

Overall, 9.8% of patients in the DOAC cohort and 15.2% of those in the warfarin cohort died in the hospital (P<0.0001). The adjusted RR for inpatient mortality was 0.66 (95% CI, 0.49 to 0.89) for DOAC-related major bleeds compared to warfarin. There were no significant differences in all-cause 30-day mortality between groups (12.6% for DOAC bleeds vs. 16.3% for warfarin bleeds; adjusted RR, 0.79; 95% CI, 0.61 to 1.03).

The study authors noted limitations, such as how the outcomes may not apply to settings other than regional referral centers and that the observational design is prone to immortal time bias and confounding by indication (patients on warfarin who died prior to the study start date were excluded). In addition, the study population was limited to patients undergoing thromboprophylaxis for atrial fibrillation.

The lower in-hospital mortality rate seen with DOACs compared to warfarin (despite high rates of warfarin reversal) is consistent with previous clinical trial findings, the authors noted. “This … suggests patients on these novel agents do not suffer excess harm compared to warfarin in the real-world context, even with the lack of specific antidotes,” they wrote. “Our findings will serve as useful baseline data for comparison of effectiveness and cost-effectiveness of drug-specific reversal agents to guide their optimal use.”