Risk of GI bleeding highest with rivaroxaban, lower with apixaban… and lowest with PPI cotherapy

Reference

Ray WA, Chung CP, Murray KT, et al. Association of oral anticoagulants and proton pump inhibitor cotherapy with hospitalization for upper gastrointestinal tract bleeding. JAMA 2018;320(21):2221-2230.

Synopsis

The risk of serious UGI bleeding associated with individual anticoagulant drug choice (with or without PPI cotherapy) is uncertain. These investigators analyzed the US Medicare beneficiary files of patients, 30 years or older, who initiated oral anticoagulation treatment with apixaban (Eliquis), dabigatran (Pradaxa), rivaroxaban (Xarelto), or warfarin. The primary outcome of interest was hospitalization for UGI bleeding that is potentially preventable by PPI cotherapy, including esophagitis, peptic ulcer disease, and gastritis. Multiple analyses occurred to control for covariates, including cardiovascular disease, low-dose aspirin prophylaxis, frailty, alcohol abuse, liver disease, history of previous UGI bleeding, current use of other medications that affect bleeding risk (eg, nonsteroidal anti-inflammatory drugs), and age/other demographic factors. A total of 1,643,123 patients had 1,713,183 new episodes of oral anticoagulant treatment from January 1, 2011, through September 30, 2015. The mean age of the patients was 76.4 years and the indication for anticoagulation was atrial fibrillation for 74.9% of them. In patients receiving anticoagulant treatment without PPI cotherapy, the adjusted incidence of hospitalization for UGI bleeding was significantly higher in those who received rivaroxaban compared with those who received dabigatran, warfarin, or apixaban (144 per 10,000 person-years vs 120, 113, and 73, respectively). For patients receiving anticoagulant treatment with PPI cotherapy, the adjusted incidence of severe UGI bleeding was lower than without cotherapy for all anticoagulants (76/10,000 per year vs 115/10,000 per year; number needed to treat = 256), although still significantly highest with rivaroxaban.