NOAC Dosing for Patients With AF and Renal Dysfunction
What are the dosing patterns of non–vitamin K antagonist oral anticoagulants (NOACs) and associated outcomes (thromboembolic and bleeding) in atrial fibrillation (AF) patients treated in routine practice?
From a large US administrative database, the authors identified 14,865 AF patients who initiated apixaban, dabigatran, or rivaroxaban between October 1, 2010 and September 30, 2015. Patients were identified if they had potential overdosing (e.g., use of standard dose in the setting of renal dysfunction) or underdosing (use of reduced dose in the setting of normal renal function). Cox proportional hazards regression was performed in propensity score matched cohorts.
Among the 1,473 patients with a renal indication for dose reduction, 43.0% were potentially overdosed. These patients were associated with a higher risk of major bleeding (hazard ratio [HR], 2.19; 95% confidence interval [CI], 1.07-4.46), but no significant difference in stroke. Among the 13,392 patients without a renal indication for dose reduction, 13.3% were potentially underdosed. The apixaban underdosed patients were associated with a higher risk of stroke (HR, 4.87; 95% CI, 1.30-18.26), but no significant difference in bleeding. The rivaroxaban and dabigatran underdosed patients were not associated with any stroke or bleeding difference.
The authors concluded that in routine clinical practice, prescribed NOAC doses are often inconsistent with drug labeling and may be associated with adverse clinical outcomes.
The authors confirmed previously reported studies that confirm a high rate of inappropriate NOAC dosing and associated poor outcomes. Clinicians should carefully review renal function (calculating the Cockcroft-Gault creatinine clearance for dabigatran, edoxaban, and rivaroxaban) and ensure that dosing follows the package label. Reviewing NOAC dosing is a potential role for many existing anticoagulation clinics to assist patients taking any oral anticoagulant.
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