As the prevalence of morbid obesity rises, it may be time to change the guidelines regarding the use of direct oral anticoagulants (DOACs) and warfarin, a vitamin K antagonist, to treat atrial fibrillation (AF) and venous thromboembolism (VTE) in patients with morbid obesity. Morbid obesity is also known as severe or grade 3 obesity and is defined as a body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) greater than 40. BMI greater than 50 constitutes extreme obesity.

“My take is that they should change the guidelines,” said Modupe Idowu, MD, associate professor in the division of hematology at the University of Texas Health Science Center at Houston. “They should recommend against DOACs for this patient population, the severely obese with a BMI greater than 40.”

Dr Idowu explained that pharmacokinetic and pharmacodynamic studies evaluating the use of DOACs in patients with morbid obesity are lacking. Issues of drug absorption, distribution, metabolism, and excretion need further investigation. This patient population often experiences problems with maintaining good anticoagulation levels. “[Treatment] always has to be individualized because some patients are just not good candidates with warfarin and can’t achieve levels that are consistent,” she said.

She went on to state that what is happening in clinical practice does not reflect the current guidelines. “The guidelines are saying it is okay to use DOACs in obese patients, and the obese patients are just lumped together as a group,” Dr Idowu noted. “This is a very controversial area, and what is happening in clinical practice is very new. DOACs are fairly new and were just introduced in the last 10 years.”

She said the guidelines need to change so that patients with extreme obesity are not grouped together with patients who are simply obese (ie, patients who have BMI of 30 or greater). Another major concern with the use of DOACs in extremely obese patients is the lack of availability of an antidote. Dr Idowu noted that the antidote andexanet alfa costs $6600 for a 200 mg dose, and patients typically need 400 mg to 800 mg followed by additional doses. If a patients comes in with a bleed, they may find the antidote is not available due to its high costs. “Most centers don’t have access,” she said.

She explained this must be considered along with the fact that patients on warfarin must be checked every week, and after the patient is stable, they must still be checked monthly or every 8 weeks. With DOACs, monitoring can be done every 6 months.

Recently published retrospective studies suggest there is a place for DOACs in patients with extreme obesity. Researchers at the Montefiore Medical Center in the Bronx, New York, retrospectively examined outcomes in 795 morbidly obese patients with either AF or VTE, 150 of whom were prescribed apixaban, 326 of whom were prescribed rivaroxaban, and 319 of whom were prescribed warfarin.1 The researchers found similar efficacy and safety profiles with the DOACs apixaban and rivaroxaban as well as warfarin in these patients. “These data, if confirmed in prospective studies, might enable patients with a BMI of at least 40 to benefit from more convenient, and possibly safer, anticoagulants,” wrote the researchers.