Evaluating the Safety and Efficacy of DOACs in Obese Patients with Venous Thromboembolism
Cherith Blair, Valana Vannoy, Khushbu Patel
Background/Purpose:
Venous Thromboembolism (VTE) is a major public health issue, affecting about 900,000 people annually in the United States, and is the leading preventable cause of in-hospital mortality. Current guidelines recommend direct oral anticoagulants (DOACs) over vitamin K antagonists, like warfarin, for VTE due to their favorable pharmacokinetic profile, fewer interactions, and lack of routine monitoring. However, the safety and efficacy of DOACs in patients with extreme body weight remain uncertain. Obesity, defined as body mass index (BMI) ≥ 30 kg/m2, is a known risk factor for VTE, with mechanistic links to venous stasis, endothelial dysfunction and hypercoagulability. Despite this, obese individuals have been underrepresented in major randomized controlled trials that assess the efficacy of DOACs in treating VTE, leading to uncertainties regarding optimal anticoagulation.
In 2016, the International Society of Thrombosis and Haemostasias (ISTH) recommended warfarin over DOACs for patients with a BMI ≥ 40 kg/m2 or weight ≥ 120 kg due to concerns of reduced drug exposure with fixed dose DOACs. Though pharmacokinetic data suggest that obese patients may achieve therapeutic levels with DOACs, more clinical evidence is needed for definitive recommendations in this patient population. In 2021, ISTH updated their stance to recommend DOACs in all patients regardless of BMI, however clinical evidence in severely obese populations remains limited. This study aimed to evaluate the safety and efficacy of DOACs in obese patients compared to non-obese patients being treated for VTE at Emory Decatur Hospital.
Methods:
This was a single-center, IRB-approved, retrospective study conducted from October 2022 through November 2024. Patients were included if they were ≥18 years of age, diagnosed with a VTE and treated with a DOAC. Patients were excluded if they were on anticoagulation for any other indication. Patients were stratified into morbidly obese and non-morbidly obese patient groups. Morbid obesity was defined as BMI ≥40 kg/m2 or weight ≥ 120 kg. The primary outcome was the incidence of recurrence of VTE within 12 months. Secondary outcomes included all-cause mortality, VTE-related mortality, and length of stay. Safety outcomes include major bleeding events, clinically relevant non-major bleeding events and adverse drug reactions.
Results:
The incidence of recurrence of VTE within 12 months occurred in 7.3% of patients in the BMI <40 kg/m2 group (n=4) and 2% of patients in the BMI ≥40 kg/m2 group (n=1) (OR 0.26, 95% CI [0.027-2.46], p-value 0.367). There was one death from all-cause mortality in the BMI ≥40 kg/m2 group and no deaths occurred in the BMI <40 kg/m2 group (p-value 0.47). No VTE related mortality was observed. The median length of stay was 50.5 hours in BMI < 40 and was 51.8 hours in the BMI ≥40 kg/m2 group (p-value 0.44). Major bleeding events occurred in 5% of patients in the BMI <40 kg/m2 group (n=3), while 6% of patients had major bleeding events in the BMI ≥40 kg/m2 group (n=1) (OR 1.13, 95% CI [0.217-5.88], p-value 1). Non-major bleeding events occurred in 12% of patients in the BMI < 40 kg/m2 (n=7) and in 6% of patients in the BMI ≥40 kg/m2 (n=3).
Conclusion:
The use of DOACs in patients with morbid obesity may be a safe and effective option for VTE treatment, with no observed increase in recurrent VTE or bleeding events. However, larger randomized controlled trials are needed to fully evaluate their efficacy and safety in this population.
