Abstract 17709: Deviation From Dosing Labels of Non-vitamin K Antagonist Oral Anticoagulants May be Associated With Reduced Effectiveness or Safety
Introduction: Dose reduction of non-vitamin K antagonist oral anticoagulants (NOACs) is indicated in atrial fibrillation (AF) patients with clinically significant renal impairment. We aimed to investigate the NOAC dosing patterns in routine practice and the associated stroke and bleeding outcomes.
Hypothesis: Failure to reduce dose in patients with severe renal disease may increase the risk of bleeding, while dose reduction without a firm indication may decrease the effectiveness of stroke prevention.
Methods: Using a large U.S. administrative database, we identified 14,865 AF patients who initiated apixaban, dabigatran or rivaroxaban between 10/1/2010-9/30/2015 We considered patients to have a renal indication for dose reduction if they were prescribed dabigatran and had a GFR <30 mL/min/1.73m2, rivaroxaban and a GFR <50 mL/min/1.73m2, or apixaban and a serum creatinine ≥1.5 mg/dL. Numerous sensitivity tests were conducted to vary the definition of indication for dose reduction. Cox proportional hazard regression was performed in propensity-score matched cohorts to investigate the outcomes.
Results: Among the 1,473 patients who met the renal indication for dose reduction, 43.0% received standard doses, which was associated with a higher risk of major bleeding (hazard ratio [HR] 2.19 [1.07-4.46], p=0.03), but no significant difference in stroke (HR 1.66 [0.40-6.88], p=0.48) in comparison to reduced doses. Among the 13,392 patients with no renal indication for dose reduction, 13.3% received reduced doses, which was associated with a higher risk of stroke (HR 4.87 [1.30-18.26], p=0.02) but no significant difference in major bleeding (HR 1.29 [0.48-3.42], p=0.61) in comparison to the standard dose in apixaban-treated patients. There was no relationship between dose reduction and stroke or bleeding in dabigatran or rivaroxaban-treated patients without a renal indication for dose reduction.
Conclusions: In routine clinical practice, the prescribed NOAC doses are often inconsistent with the FDA labeling. These prescribing patterns may be associated with increased risk of major bleeding in patient with severe kidney disease and reduced effectiveness in apixaban-treated patients with normal or mildly impaired renal function.
Author Disclosures: X. Yao: None. N.D. Shah: None. L.R. Sangaralingham: None. B.J. Gersh: Consultant/Advisory Board; Modest; Medtronic Inc, Baxter Healthcare Corporation, Cardiovascular Research Foundation, St. Jude Medical, Ortho-McNeil-Janssen Pharmaceuticals, Teva Pharmaceuticals, Boston Scientific, Pfizer. P.A. Noseworthy: None.
- © 2016 by American Heart Association, Inc.