Recurrent GI Bleeding: Warfarin vs Direct Oral Anticoagulants

SAN ANTONIO – Resumption of warfarin post-hospitalization for gastrointestinal bleeding (GIB) was associated with an increased risk for recurrent GIB compared with direct oral anticoagulants (DOACs), according to findings reported at the American College of Gastroenterology 2019 Annual Scientific Meeting held October 25-30 in San Antonio, Texas.

DOACs represent an emerging class of anticoagulants that have become increasingly popular in the last several years. DOACs include apixaban, rivaroxaban, dabigatran, and edoxaban.  The retrospective analysis evaluated the risk for recurrent GIB and thromboembolism (TE) in patients taking DOACs compared with patients taking warfarin after hospitalization for GIB.

The researchers analyzed an IBM MarketScan® Research Database from January 2008 to December 2017. Adult patients with a history of atrial fibrillation or AFib treatment with either DOACs or warfarin and hospitalized for GIB were evaluated along with post-discharge readmissions for recurrent GIB and TE within 180 days of initial discharge.  

A total of 2991 patients were identified (warfarin, 1872 patients; DOACs, 1121).  Of the patients on warfarin, 29% resumed their medication following discharge with a median time to resumption of 27 days compared with 16% of patients on DOACs with a median time to resumption of 32 days. Discharge on warfarin had the highest risk for recurrent GIB (hazard ratio [HR], 1.69; 95% CI, 1.23-2.31) compared with dabigatran (HR, 0.13; 95% CI, 0.02-0.90) and apixaban (HR, 0.38; 95% CI, 0.14-1.01) which had a lower risk for current GIBs. Overall, the resumption of warfarin was associated with an increased risk for recurrent GIB (HR, 1.53; 95% CI, 1.07-2.18) compared with DOAC resumption (HR, 0.85; 95% CI, 0.51-1.42) using a multivariable cox regression model.  

Additional statistically significant differences between the warfarin and DOAC groups included the number of patients on thienopyridines (16.7% vs 11.5%, respectively; P <.001), prior history of TE (12.4% vs 5.3%, respectively; P <.001), history of end-stage renal disease (5.9% vs 1.3%, respectively; P <.0001), and prior history of GIB (12.4% vs 9.4%, respectively; P =.01), respectively. Patients on DOACs more frequently underwent endoscopy (46.8% vs 39.9%, respectively; P =.0002) and colonoscopy (63.4% vs 57.4%, respectively; P =.0008). However, the number of patients undergoing endoscopic intervention was not significantly different between the groups. Patients on DOACs had bleeding sources more commonly found to be esophagitis (6% vs 4%, respectively; P =.02), diverticulosis (27.4% vs 22.8%, respectively; P =.005), and hemorrhoidal (12.2% vs 8.0%, respectively, P =.0002), while patients on warfarin were more likely to have duodenal ulcers (6.5% vs 4.5%, respectively; P =.02) as the bleeding source.  

There was no statistical difference in the number of patients receiving blood transfusions or requiring intensive care unit admission; however, patients in the warfarin group received more fresh frozen plasma (17.4% vs 4.0%, respectively; P <.0001). Overall median length of stay was slightly shorter in the DOAC group compared with the warfarin group (3 vs 4 days, respectively; P <.0001). The investigators concluded that resuming warfarin after hospital discharge for GIB was associated with an increased risk for recurrent GIB compared with DOACs. 

Many of the study findings could be attributed to the pharmacologic differences between warfarin and DOACs, including the shorter half-life of DOACs, availability of reversal agents at the time of study (fresh frozen plasma for warfarin), certain PMH of the warfarin group (end-stage renal disease, prior GIB, and TE), and amount of polypharmacy in the warfarin group with thienopyridines. 

References

Tapaskar N, Ham S, Sengupta N. Risks of recurrent bleeding in patients hospitalized with gastrointestinal bleeding while on warfarin vs direct oral anticoagulants. Abstract presented at the: American College of Gastroenterology 2019 Annual Scientific Meeting; October 25-30, 2019; San Antonio, Texas. Abstract P0399.