You Make the Call: Which direct oral anticoagulant would you choose for a saddle pulmonary embolism?

Allyson Pishko, MD, MSCE
Assistant Professor, Division of Hematology/Oncology, University of Pennsylvania

This month, Allyson Pishko, MD, MSCE, discusses choice of direct oral anticoagulant (DOAC) for a saddle pulmonary embolism.

And don’t forget to check out next month’s clinical dilemma – send in your responses for a chance to win an ASH Clinical News-themed prize!

CLINICAL DILEMMA

I am caring for a female patient with obesity (134 kg) who had an unprovoked saddle submassive pulmonary embolism that required thrombolytic therapy. I am wondering whether to use the maintenance dose of rivaroxaban 10 mg, or apixaban 2.5 mg twice per day, or something else. What would you recommend regarding use of a DOACs for this patient?

EXPERT OPINION

International Society on Thrombosis and Hemostasis (ISTH) guidelines published in 2016 suggest that clinicians should not use DOACs in patients with body mass index (BMI) >40 kg/m2 or weight >120 kg for treatment of venous thromboembolism (VTE).1 More recent analyses suggest DOACs may be effective in treating VTE in this population, however. Tzu-Fei Wang, MD, and Marc Carrier, MD, outlined these studies in depth in their March 2020 “How I Treat” article in Blood.2 To summarize two key studies from their review:

  • A pooled post-hoc analysis of patients with body weight >120 kg from the EINSTEIN-DVT/PE studies reported a similar incidence of recurrent VTE in patients treated with rivaroxaban (3/159 [1.8%]) vs. enoxaparin/warfarin (4/144 [2.8%]).3
  • A retrospective cohort of patients with BMI >40 kg/m2 found a similar incidence of recurrent VTE in patients treated with rivaroxaban vs. apixaban vs. warfarin (1/47 (2.1%), 3/142 (2.1%), and 2/167 (1.2%), respectively; p=0.74].4

Despite this progress, we still lack adequate randomized controlled trials of DOACs for VTE treatment in extremely obese patients. For this patient, who weighs 134 kg, I would present warfarin as the preferred oral anticoagulant. If she did not want warfarin therapy, I would propose a DOAC as an alternative (and one with growing evidence to support its safety and efficacy).

If this patient opted for a DOAC and was tolerating therapeutic intensity anticoagulation, I would not change to a prophylactic dose at 6 months (an approach I often take in non-morbidly obese patients).5,6 Data support the use of DOACs for primary VTE prevention in morbid obesity at standard prophylactic dosing (e.g., apixaban 2.5 mg twice daily or rivaroxaban 10 mg daily).7 There remains a paucity of data on prophylactic-dose DOACs for extended VTE treatment in morbid obesity. However, I would certainly consider reducing to a prophylactic dose if this patient had any bleeding issues or need for concurrent antiplatelet therapy.

Generally, the need for thrombolytic therapy would not change my choice of anticoagulant after hospital discharge. In this patient’s case, I would be more partial to using warfarin due to the life-threatening nature of her event and lack of robust data for DOACs in patients >120 kg. One approach would be to treat with warfarin during at least the highest-risk period for VTE recurrence (the first 1 to 3 months), then transition to DOAC if preferable. Fortunately, data continue to accumulate on this topic, and my practice continues to evolve. Shared decision making with the patient remains key when selecting the long-term anticoagulation strategy.

References

  1. Martin K, Beyer-Westendorf J, Davidson BL, et al. Use of the direct oral anticoagulants in obese patients: guidance from the SSC of the ISTH. J Thromb Haemost. 2016;14(6):1308-1313.
  2. Wang T-F, Carrier M. How I treat obese patients with oral anticoagulants. Blood. 2020;135(12):904-911.
  3. Nisio MD, Vedovati MC, Riera-Mestre A, et al. Treatment of venous thromboembolism with rivaroxaban in relation to body weight. Thromb Haemostasis. 2016;116(04):739-746.
  4. Kushnir M, Choi Y, Eisenberg R, et al. Efficacy and safety of direct oral factor Xa inhibitors compared with warfarin in patients with morbid obesity: a single-centre, retrospective analysis of chart data. Lancet Haematol. 2019;6(7):e359-e365.
  5. Weitz JI, Lensing AWA, Prins MH, et al. Rivaroxaban or Aspirin for Extended Treatment of Venous Thromboembolism. New Engl J Med. 2017;376(13):1211-1222.
  6. Agnelli G, Buller HR, Cohen A, et al. Apixaban for Extended Treatment of Venous Thromboembolism. New Engl J Med. 2013;368(8):699-708.
  7. Pathak R, Karmacharya P, Giri S, et al. Meta-analysis on efficacy and safety of new oral anticoagulants for venous thromboembolism prophylaxis in overweight and obese postarthroplasty patients. Blood Coagul Fibrin. 2015;26(6):635-642.

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NEXT MONTH'S CLINICAL DILEMMA

An 82-year-old asymptomatic patient presented with an elevated white blood cell count of 24×109 cells/L, a hemoglobin level of 11 g/dL, a platelet count of 56×109/L, and an absolute lymphocyte count of 20×109 cells/L. The marrow was hypercellular (80%-90%) with small lymphocytes representing 70%-80% of the marrow cellularity. By flow cytometry, the lymphocytes were CD20-expressing and kappa light chain–restricted B cells, and were negative for CD10, CD200, and BCL1. A subset showed dim CD5 expression, but CD5 was largely negative and the cells were also negative for CD19, CD23, FMC7, CD11c, and CD38. Cytogenetics showed deletion 7q, an unbalanced translocation between 3q and 21p resulting in gain of 3q; monosomy 17/deletion of TP53, and other aberrations in 17/20 cells. MYD88 was wild type. The pathologists characterized this a low-grade B-cell lymphoma, either marginal zone or something else. My concern is about the TP53 loss and use of single-agent rituximab with likely shorter time to progression and survival. I am favoring instead using ibrutinib upfront given poor cytogenetics and would appreciate your thoughts.

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