Case Presentation: A 50 year-old African American female with medical history of morbid obesity (BMI 40.8), hypertension, hyperlipidemia, diabetes mellitus, obstructive sleep apnea, atrial fibrillation, right MCA infarct one year prior to admission, and right renal infarct one month prior to admission presented with two days of sharp left-sided abdominal pain associated with non-bloody and non-bilious emesis. For over a year, the patient had been taking dabigatran 150mg twice daily for atrial fibrillation and reported medication adherence leading up to this episode.
Initial laboratory values showed creatinine of 0.9 mg/dl, which was stable from baseline. Abdominal CT revealed a new wedge shaped low-attenuation region in the lower pole of left kidney, likely representing a new renal infarction. Given multiple thrombo-embolic events while taking dabigatran, the patient was started on a heparin drip, then bridged to warfarin prior to discharge for a more reliable form of anticoagulation
Discussion: As direct oral anticoagulants (DOACs) are increasingly administered, it is important to evaluate efficacy in different patient populations. Dabigatran is a small molecule that acts as a reversible, competitive, direct thrombin inhibitor. Currently, dabigatran is recommended in fixed dosing, regardless of weight. Trials have so far shown conflicting outcomes of dabigatran in patients weighing over 100 kg. Further, in randomized control trials clinical trials testing DOACs, obese patients with BMIs of greater than 40 kg/m2 or weight greater than120 kg have been underrepresented. Several published cases report dabigatran failure in obese patients, with a few proposed mechanisms. Of all the DOAC’s, dabigatran has the highest volume of distribution and is the least protein bound. Because dabigatran is highly lipophilic with a high volume of distribution, the drug distribution in excess adipose tissue in obese patients may lead to decreased drug levels. In addition, dabigatran is 80% renally cleared, which could lead to sub-therapeutic levels in younger, obese patients with a higher creatinine clearance.
Conclusions: This case illustrates repeated failure of dabigatran in an obese patient with a high creatinine clearance, which may become an issue faced by hospitalists as DOAC’s are increasingly prescribed. Due to repeated failure on a DOAC, this patient was bridged to warfarin for regular monitoring of her INR and prevention of further embolic events. The theoretical risk of increased dabigatran failure in obese patients has not been validated through randomized control trials, partially due to the small number of patients at extremes of body weights in prior clinical trials. Further elucidation of studies regarding factors which may cause sub-therapeutic levels of dabigatran in obese patients and subsequent consideration of dosing regimens should be addressed.