LAUSR

To the Editor: Dabigatran is a novel oral anticoagulant agent that can be used in fixed-dose regimens for anticoagulation in patients with atrial fibrillation, deep venous thrombosis (DVT), or pulmonary embolism (PE). However, the scientific evidence of its anticoagulation efficacy is lacking in morbidly obese patients (body mass index [BMI] > 40). Clinical guidelines recommend no dose adjustments of dabigatran with regard to the patient's body weight and recommends a fixed dose of 150 mg twice daily for DVT/PE prophylaxis. A 57-year-old male with a past medical history of DVT, essential hypertension, diabetes mellitus type 2, paroxysmal atrial fibrillation, and gastric bypass surgery was admitted to the hospital with a submassive PE and underwent catheter-directed thrombolysis (EKOS System; EKOS Corp., Bothell, WA). His BMI was 44.29 kg/m, and he weighed 132 kg on admission. The patient had been taking dabigatran for 6 years and was initially started on warfarin for DVT before eventually shifting to dabigatran for concomitant new onset paroxysmal atrial fibrillation. The patient reported being in good health 1 month prior to admission, when he noticed progressive exertional dyspnea associated with increased fatigue and limitation in activity. This was associated with a dry cough and increased bilateral lower extremities edema. He recently had a 3-hour airplane journey. He denied all forms of tobacco use or any drug abuse. On presentation, he was noted to have tachycardia and hypoxia in the emergency department. Cardiothoracic angiogram of the chest showed a large volume of thrombus within the right main pulmonary artery that was nearly occlusive. Thrombus extends into the segmental and subsegmental branches of the right upper, middle, and lower lobes. Extensive thrombosis of the distal left main pulmonary artery extending into segmental and subsegmental branches of the left upper lung lobe was also noted. Bowing of the interventricular septum suggestive of right heart strain was noted, which was confirmed on transthoracic echocardiogram. Brain natriuretic peptide was elevated to 2615, but no elevation in troponin levels was noted. The patient underwent emergent catheter-directed thrombolysis (EKOS System) during which 1 mg/h of alteplase was administered for 12 hours through the catheters. He was eventually transferred to the intensive care unit for further monitoring. Dabigatran was changed to rivaroxaban for life-long anticoagulation, and the patient was discharged. During this course of hospital stay, the patient's dabigatran trough levels were never checked, but his compliance with the medication was confirmed both from the patient and the pharmacy. The likely causes of failure of anticoagulation of dabigatran in this case might be related to gastric bypass surgery history and proton pump inhibitor use, which are known to affect the dabigatran trough levels. To our knowledge, 2 cases have been previously reported in obese patients on dabigatran who presented with a thromboembolic event. Both of these patients had comparatively lower trough levels, which was likely related to the pharmacokinetics of the drug itself. The RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial showed that patients who weighed >100 kg had 20% less dabigatran trough levels compared to those who weighed less. However, no difference of efficacy between dabigatran and warfarin was reported in patients with a BMI of 25–35 kg/m. Contrary to this, Liesenfeld et al studied a subset of the RE-LY population and concluded that no dosage changes for dabigatran are required based on the patient's weight. Therefore, the scientific evidence of the use of dabigatran in morbidly obese patients is confusing and warrants large-scale studies. In conclusion, a fixed-dose regimen of dabigatran may not be effective for PE and DVT prophylaxis in morbidly obese patients. Usama Nasir MD Department of Medicine, University of Connecticut Health Center, Farmington, Connecticut DOI 10.1002/clc.22755