By Anne Harding
NEW YORK (Reuters Health) - 13/6/2019
"In patients with a BMI of at least 40 there didn't seem to be more thrombotic events or bleeding events in those who were on direct oral anti-Xa inhibitors compared to the ones on Coumadin," Dr. Margarita Kushnir of Montefiore Medical Center, in New York City, the study's lead author, told Reuters Health by phone.
Morbidly obese patients are poorly represented in clinical trials of direct oral anticoagulants for AF and VTE, Dr. Kushnir and her team note in The Lancet Haematology, online May 24. They retrospectively analyzed chart data for 795 adults with BMIs of 40 and above who had been prescribed apixaban, rivaroxaban, or warfarin for AF or VTE.
Among the 366 patients with VTE, recurrent VTE incidence was 2.1% with apixaban, 2.0% with rivaroxaban and 1.2% with warfarin (P=0.74) and major bleeding occurred in 2.1%, 1.3% and 2.4%, respectively (P=0.77).
Incidence of stroke was also similar across the three drugs for the 429 patients prescribed anticoagulants for AF. Major bleeding occurred in 2.9% of AF patients on apixaban, 2.9% of those on rivaroxaban, and 7.9% of those on warfarin (P=0.063).
"This is the largest study to date examining morbidly obese patients on direct oral anticoagulants and provides further evidence of similar efficacy and safety between direct oral anti-Xa inhibitors and warfarin in morbidly obese patients with atrial fibrillation and venous thromboembolism," the authors write.
"Although the overall low incidence of events in our study population was reassuring, a randomised controlled trial is needed to enable patients with morbid obesity to benefit from more convenient therapies, which might also offer a net clinical benefit," they conclude.
"It's a retrospective study, but it's reassuring that these rates are so low," Dr. Kushnir said. "I feel personally safer using these drugs in patients with morbid obesity."
In an editorial accompanying the study, Dr. Paul L. Den Exter and Dr. Menno V. Huisman of Leiden University Medical Center in the Netherlands note that the chief issue with fixed-dose direct oral anticoagulants in morbidly obese patients is the drugs' activity profile, as studies suggest that higher body weight is associated with lower peak and trough concentrations.
"Although, by definition, this observational study was not designed to prove non-inferiority for direct oral anticoagulants, the low rates of recurrent venous thromboembolism events and stroke make it possible to conclude that the clinical outcome of morbidly obese patients treated with direct oral anticoagulants at a fixed dose is unlikely to differ from those treated with warfarin," they add.
"Confirmation of these data by future investigations, preferably supported by measurements of direct oral anticoagulant concentrations, would be needed before changing the consensus that direct oral anticoagulants should be used with caution in patients with severe obesity," they conclude.
The study had no funding. Dr. Kushnir and one of her coauthors report ties to companies that sell direct oral anticoagulants.
Lancet Haematol 2019.