A Patient Needing Concomitant P-gp Substrate and Inhibitor

A 76-year-old woman with atrial fibrillation (CHADS2 score = 3) on warfarin presents to her cardiologist following multiple missed appointments at the anticoagulation clinic. She has had two visits to the Emergency Department over the past year for minor gastrointestinal bleeds in the setting of supratherapeutic INR. The patient is asymptomatic in clinic but confirms that she is unable to reliably attend the anticoagulation clinic appointments because the commute is too difficult for her.

The patient has history notable for permanent atrial fibrillation, hypertension, diabetes mellitus type 2, and stage III chronic renal insufficiency (CrCl 40 mL/min), without any prior history of TIA, stroke, coronary heart disease, or heart failure. Her outpatient medications include warfarin, dronedarone, atorvastatin, amlodipine and benazepril. Laboratory values in clinic are notable for INR 3.4 (goal 2-3).

After evaluation of the risks and benefits of various anticoagulation strategies in this patient, the cardiologist decides to discontinue warfarin and initiation dabigatran therapy for primary stroke prevention in the setting of non-compliance with warfarin.

Which of the following is the most appropriate strategy for initiation of dabigatran in this patient?

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