PHILADELPHIA – Dabigatran and rivaroxaban, which are rapidly replacing warfarin for anticoagulation in patients with atrial fibrillation, appear to be associated with a greater risk of GI bleeding than the long-time standard in patients over the age of 65 years, according to an analysis presented at the American College of Gastroenterology (ACG).
The pattern of an increased GI bleeding risk with the newer oral anticoagulants relative to warfarin was consistent in older patients whether used for AF or for out-of-labeling indications, which were assessed separately, reported Dr. Neena S. Abraham, professor of medicine at Mayo Clinic, Scottsdale, Ariz.
Dr. Neena S. Abraham
“In all four cases, once patients were over the age of 65, the risk of GI bleeding increased significantly on the novel agents when compared to warfarin,” Dr. Abraham reported.
The propensity matches, based on such characteristics as GI bleeding risk factors, age, race, and concomitant medications, were drawn from 92,816 patients in a large database starting a new prescription of dabigatran, rivaroxaban, or warfarin over a recent 3-year period. With this matching, 9,860 new users of dabigatran and 20,619 new users of rivaroxaban were compared with equal number of new users of warfarin.
In the full dataset, before age stratification, the risk of total GI bleeding, particularly lower GI bleeding, appeared to be nonsignificantly lower for both dabigatran and rivaroxaban, relative to warfarin in patients with AF. In patients without AF receiving these drugs, the risk remained slightly lower on rivaroxaban but appeared to be slightly increased on dabigatran.
However, the hypothesis that bleeding risk was greater for newer agents in older patients was substantiated when the data were stratified by age. In the analysis, risk of bleeding started climbing more steeply with the newer agents as patients aged than with warfarin, with differences observed at about age 65 years.
By age 75, the hazard ratio for a GI bleed in dabigatran patients relative to warfarin in AF patients was 2.4 (95% confidence interval 1.5-3.8). In the rivaroxaban group, the HR for this risk at age 75 in AF patients was 4.0 (95% CI 2.1-7.4). In non-AF patients, the rates of GI bleeding were also significantly increased at a similar magnitude.
These data were anticipated by the initial trials that found dabigatran and rivaroxaban noninferior to warfarin for the prevention of stroke and systemic embolism, according to Dr. Abraham. Although there was heterogeneity in reported risk differences, she reported that GI bleeding was as much as 25% higher on the newer anticoagulants when compared to warfarin in older patients. These new data substantiate those findings.
“Our study is the first to evaluate GI safety in novel oral anticoagulants compared to warfarin in a real-world, multiage setting,” Dr. Abraham noted. She said these data “facilitate risk-benefit considerations” of these drugs. She further noted that the data on non-AF patients may be particularly pertinent “because this is the fastest-growing emerging market” for agents in this class.
Asked for a comment, Dr. Brian E. Lacy, chief of gastroenterology and hepatology at Dartmouth-Hitchcock Medical Center, Lebanon, N.H., said that the information about relative risk is potentially important, but he was particularly impressed by the substantial use of novel anticoagulants in non-AF patients.
“This tells me that we as gastroenterologists need to be asking more questions about exposure to anticoagulants,” Dr. Lacy said in an interview. “These data suggest that these newer drugs are being used frequently outside of labeling. We need to be aware of these changing patterns of use when trying to assess the risk of our patients for GI bleeds.”
Dr. Abraham had no financial disclosures.