Characteristics and outcomes in patients with atrial fibrillation receiving direct oral anticoagulants in off-label doses.

Briasoulis A, Gao Y, Inampudi C, Alvarez P, Asleh R, Chrischilles E, Leira EC, Vaughan-Sarrazin M. Characteristics and outcomes in patients with atrial fibrillation receiving direct oral anticoagulants in off-label doses. BMC cardiovascular disorders. 2020 Feb 3; 20(1):42.

Dimensions for VA is a web-based tool available to VA staff that enables detailed searches of published research and research projects.

If you have VA-Intranet access, click here for more information vaww.hsrd.research.va.gov/dimensions/

VA staff not currently on the VA network can access Dimensions by registering for an account using their VA email address.    Search Dimensions for VA for this citation
* Don't have VA-internal network access or a VA email address? Try searching the free-to-the-public version of Dimensions

Search for Abstract from PubMed

---

Abstract:

BACKGROUND: We evaluated adherence to dosing criteria for patients with atrial fibrillation (AF) taking dabigatran or rivaroxaban and the impact of off-label dosing on thromboembolic and bleeding risk. METHODS: We used data for a retrospective cohort from a large U.S. health plan for Medicare beneficiaries age > = 65 years with AF who initiated dabigatran or rivaroxaban during 2010-2016. Stroke and major bleeding were quantified in patients who were eligible for low dose but received standard dose, and in patients who were eligible for standard dose but received low dose. RESULTS: We identified 8035 and 19,712 patients who initiated dabigatran or rivaroxaban, respectively. Overall, 1401 (17.4%) and 7820 (39.7%) patients who received dabigatran and rivaroxaban met criteria for low dose, respectively. Of those, 959 (68.5%) and 3904 (49.9%) received standard dose. In contrast, 1013 (15.3%) and 2551 (21.5%) of patients eligible for standard dose dabigatran and rivaroxaban received low dose. Mean follow-up for patients eligible for low and standard dose dabigatran and rivaroxaban were 13.9, 15.1, 10.1, and 12.3 months, respectively. In unadjusted analyses, patients eligible for low or standard dose dabigatran and rivaroxaban but receiving off-label dose, had no differences in the rates of ischemic stroke. Among patients who met criteria for standard dose direct oral anticoagulants (DOAC), use of low dose was associated with significantly higher risk of any major bleeding (Dabigatran: HR = 1.44; 95% CI 1.14-1.8, P = 0.002, Rivaroxaban HR 1.34, 95% CI 1.11-1.6, P = 0.002) and gastrointestinal bleeding (Dabigatran: HR = 1.48; 95% CI 1.08-2, P = 0.016). In patients who met criteria for low dose DOACs, there was lower risk of major bleeding (Dabigatran: HR = 0.59; 95% CI 0.43-0.8, P < 0.001), gastrointestinal (Rivaroxaban: HR 0.79; 95% CI 0.64-0.98, P = 0.03) and intracranial bleeding (Dabigatran: HR = 0.33; 95% CI 0.12-0.9, P = 0.001) with standard dosing. After propensity matching, use of off-label doses was not associated with stroke, major, gastrointestinal or intracranial bleeding for either dabigatran or rivaroxaban. CONCLUSIONS: While a significant number of patients receive higher or lower dose of dabigatran and rivaroxaban than recommended, we found no evidence of significant impact on thromboembolic or hemorrhagic outcomes.