Impact of oral anticoagulant choice for the secondary prevention of venous thromboembolism on the risk of inpatient bleeding

Abstract

Background Randomized trials suggest that direct oral anticoagulants (DOACs) are at least as effective as warfarin for primary treatment of VTE and that bleeding risk may be lower for some DOACs relative to warfarin. However, there is very little information regarding potential bleeding risks for DOACs versus warfarin in secondary prevention of VTE. Objective The aim of this study was to compare rates of bleeding events resulting in inpatient admissions between individuals taking apixaban, rivaroxaban, and warfarin for secondary prevention of VTE during the period 2013‐2017. Methods We used the IBM MarketScan Commercial Claims and Encounters Database and Medicare Supplemental and Coordination of Benefits Database (IBM Watson Health, Ann Arbor, MI) to establish a retrospective cohort. Initial venous thrombolism events were defined from medical claims, and follow‐up for this cohort began 6 months after the initial event. Bleeding events resulting in inpatient admission were identified from claims data over the subsequent year of secondary prevention. Results A total of 69 264 individuals were identified for the cohort, with 567 bleeding events. The crude rate of bleeding was highest among warfarin users (1.47/100 person‐years; 95% confidence interval [CI], 1.24‐1.74) and lower among those on either apixaban (1.00/100 person‐years; 95% CI, 0.65‐1.54) or rivaroxaban (0.84/100 person‐years; 95% CI, 0.66‐1.08). In multivariable adjusted Cox models, those on apixaban (hazard ratio [HR], 0.80; 95% CI, 0.50‐1.29) and rivaroxaban (HR, 0.81; 95% CI, 0.59‐1.09) had somewhat lower rates of bleeding events relative to those on warfarin. Conclusions We found modest evidence of decreased risk of bleeding for apixaban and rivaroxaban. These estimates were relatively imprecise.

Epidemiology and prevention of venous thromboembolism

“…Bleeding is a complication of every anticoagulant therapy. Historically, the incidence of bleeding after diagnosis of VTE has been shown to be >10%, and early bleeding is associated with a greater risk of VTE recurrence and death 199 , 200 . Data from phase III, randomized, controlled trials suggest that the use of direct oral anticoagulants, instead of warfarin, for the primary treatment of VTE could reduce the risk of bleeding 201 , 202 , but patient characteristics might influence the magnitude of the benefit 203 , 204 .…”