Secondary Prophylaxis with Reduced Dose Apixaban in the Morbidly Obese

Background: Studies examining the use of standard dosing of direct oral anticoagulants (DOACs) in the morbidly obese (BMI>40 kg/m2) in the acute venous thromboembolism (VTE) setting have demonstrated good safety and efficacy. After this initial period of therapeutic anticoagulation, DOAC dose reduction for secondary prophylaxis has become standard practice for the general VTE population. What is not known is whether the truly morbidly obese population can also be candidates for dose reduction when used after the initial therapeutic period.

Methods: This investigation examined the outcome of adult patients seen at our large diverse inner-city medical center who had a documented acute VTE from 1/1/2016-12/31/2023. Patients who had been treated with therapeutic anticoagulation for at least 3 months, but less than 15 months, and who were then switched to apixaban 2.5mg bid as the extended, secondary prophylaxis dose at a time when their BMIs were >39 kg/m2 were included in the analysis. Patients were followed for one year from the time of dose decrease. If dosing was discontinued or changed before the year, the time of change or discontinuation was considered the censored date. Patients’ medical records were initially pulled via a query of the hospital database. Data collected included general demographics, site of initial thrombosis, recurrent thrombosis, new clinically significant nonmajor bleeding (CSNMB) and major bleeds, cancer, comprehensive antiphospholipid antibody (APS) testing, as well as creatinine and hemoglobin levels at the time of dose reduction. Records were evaluated by at least one of the authors and appropriate cases confirmed by a second (HHB). All questionable cases were evaluated by at least two reviewers.

Results: The query yielded 255 cases of which only 40 were able to be included in the study. 215 cases did not fit one or more of the criteria. 102 patients were treated for non-acute VTE indications: 49 were treated for atrial fibrillation or other arterial/cardiac/valve indications, 4 had chronic deep venous thromboses (DVTs), 6 had only superficial VTE, 28 only received apixaban low dose as COVID prophylaxis, 13 were prescribed low dose for surgical prophylaxis and 2 for TTP maintenance. 43 patients lacked adequate VTE documentation (33 patients did not have an acute clot, 10 only had unconfirmed outside imaging and/or outside continued care), and 47 patients did not meet the queried criteria at the time of dose reduction (6 with creatinine levels >2mg/dl, 40 with BMIs <39kg/m², 1 pediatric patient). 21 patients were dose reduced out of the allowed time window, and 23 patients received different dosages or were noted to be nonadherent.

Of those who met criteria, average BMI was 45.9 (±5.4) kg/m2, average age: 54.4 (±12.8) years. There were 32 females and 8 males. 21 patients self-identified as Black, 7 Hispanic, 10 White, and 2 were mixed/other. 17 patients had isolated DVTs while 23 had pulmonary emboli (PE) with or without DVTs. Of these PEs, 13 were lobar or segmental, 4 bilateral, 1 saddle, 4 submassive, and 1 massive. Five patients had cancer (endometrial, breast, JAK2+ essential thrombocythemia, multiple myeloma and B cell lymphoma). 17 patients tested negative for APS, 23 were not tested. Four patients had had bariatric surgery but were still all >39 kg/m2 at time of dose reduction. Average creatinine was 0.9 mg/dl (±0.3); average hemoglobin level was 12.3 g/dl (±1.6).

The duration of initial therapeutic anticoagulation was 0.65 years (IQR 0.32). Average follow-up was 331.5 (IQR 78.2) days. Of evaluable patients, there were no recurrent clots within one year of the dose reduction. Two patients suffered hemorrhagic complications after dose reduction: One had an acute-on-chronic subdural hematoma on day 168, and another presented with a CSNMB gastrointestinal hemorrhage on day 62, was found to have a large adenoma, and then resumed anticoagulation without further issues.

Conclusion: This small study, with in-depth patient data analysis, suggests that the rates of VTE and bleeding in morbidly obese patients on long-term dose reduced apixaban may be similar to those in non-obese patients. To our knowledge, this is the first analysis of dose reduction in the morbidly obese for use as secondary prophylaxis after acute VTE treatment. Larger prospective studies will be necessary to determine whether reduced dose apixaban is useful as extended therapy in these higher risk patients.