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Antiphospholipid Syndrome: Can the New Oral Anticoagulants Be Used?

| Anticoagulants, Anticoagulents, Antiphospholipid antibodies, Edoxaban, Eliquis, Pradaxa (dabigatran), Warfarin (Coumadin), Xarelto (Rivaroxaban) | Comments Off on Antiphospholipid Syndrome: Can the New Oral Anticoagulants Be Used?

Stephan Moll, MD and Damon Houghton, MD write … In patients with antiphospholipid syndrome (APS) who require anticoagulation for the treatment of DVT or PE, warfarin or a low molecular weight heparin have traditionally been used. A question that comes up is whether one of the new oral anticoagulants (DOACs) can be effectively and safely used instead.

It is not known at this point whether DOACs are equally, more or less effective as/than warfarin in patients with APS.  Data from clinical trials directly comparing DOACs with warfarin are not yet available. Given the absence of data, no formal recommendations or guidelines exist on this topic. It is an individualized decision between a physician and patient with APS whether to use warfarin or a DOAC for the treatment of DVT or PE.

Published Data

Several case reports and case series of patients with APS treated with a DOAC have been published. All data (from a total of 122 patients) have recently been summarized [1]: Sixteen percent of patients had a recurrent clot on a DOAC. Given this relatively high rate of DOAC failure, the authors caution about the use of DOACs in APS.  However, it is also known that warfarin has a high failure rate [references 2,3]. In addition, due to the nature of case report publications (potential bias; absence of control group), no strong or meaningful conclusion is possible as to how DOACs compare to warfarin or LMWH in the treatment of DVT and PE in patients with APS.

Ongoing Studies

Several studies on APS and the use of DOACs are ongoing, with details available at clinicaltrials.gov:

  1. NCT02157272: A Prospective, Randomized Clinical Trial Comparing Rivaroxaban with Warfarin in High Risk Patients With Antiphospholipid Syndrome (TRAPS)
  2. NCT02295475: Apixaban for the Secondary Prevention of Thromboembolism Among Patients With the AntiphosPholipid Syndrome (ASTRO-APS)
  3. NCT02116036: Rivaroxaban for Antiphospholipid Antibody Syndrome (RAPS)

Our practice

We discuss with patient with APS who needs to be on an anticoagulant:

  1. … that no solid data exist regarding the use of DOACs in APS, and that it is not known whether the DOACs are as effective as warfarin, less effective or more effective.
  2. … that some patients with APS develop new clots in spite of being on warfarin and that recurrent clots may also occur on a DOAC.

If we decide to use a DOAC, then our preference is typically a twice daily dosed anticoagulant (Eliquis® or Pradaxa®) rather than a once daily dosed drug (Xarelto® or Savaysa®), as the twice daily dosed drug leads to more steady drug levels throughout the day. The hypothesis is that this may lead to a more effective anticoagulant effect. However, this theory is unproven and whether this truly leads to a lower risk of anticoagulant failure in patients with APS is not known.  A recent publication (case report plus discussion on drug pharmacokinetics/-dynamics) also suggests a twice daily rather than a once daily dosed drug in patients with APS if a DOAC is used [ref 4]. However, feasibility/practicality of once daily versus twice daily medication and, thus, patient preference, is also important to consider.

References

  1. Dufrost V et al. Direct oral anticoagulants use in antiphospholipid syndrome: Are these drugs an effective and safe alternative to warfarin? A systematic review of the literature. Curr Rheumatol Rep 2016;18:74.
  2. Crowther M et al. A Comparison of two intensities of warfarin for the prevention of recurrent thrombosis in patients with the antiphospholipid antibody syndrome. N Engl J Med 2003;349:1133-8.
  3. Finazzi G et al. A randomized clinical trial of high-intensity warfarin vs. conventional antithrombotic therapy for the prevention of recurrent thrombosis in patients with the antiphospholipid syndrome (WAPS) J Thromb Haemost 2005;3: 848–853.
  4. Schofield JR et al. Dosing considerations in the use of the direct oral anticoagulants in the antiphospholipid syndrome. J Clin Pharm Ther. 2017 Jun 27. doi: 10.1111/jcpt.12582. [Epub ahead of print].

 

Disclosure: Dr. Moll has consulted for Janssen Pharmaceuticals and Boehringer-Ingelheim. Dr. Houghton has no disclosures.

Last updated:  July 5th, 2017

New Oral Anticoagulant FDA Approved – Bevyxxa (Betrixaban)

| Anticoagulents, Therapy | Comments Off on New Oral Anticoagulant FDA Approved – Bevyxxa (Betrixaban)

Stephan Moll, MD writes… On June 23, 2017, the FDA approved a 5th new oral anticoagulant for clinical use, Bevyxxa® (= Betrixaban). It is approved to prevent DVT and PE in patients who are significantly immobile during and after hospitalization for an acute medical illness. Full prescribing information: here.  FDA details: here.

In the APEX study that led to FDA approval (reference 1), Bevyxxa® was given for 5-6 weeks during and after hospitalization to patients with acute medical illnesses (heart failure, respiratory failure, infectious disease, rheumatic disease, or stroke) who had reduced mobility and were at high risk for VTE. It was compared to 10 +/- 4 days of Enoxaparin at prophylactic dose. Fewer VTE (composite of asymptomatic proximal DVT and symptomatic VTE) occurred in the patients treated with Bevyxxa®, without a higher rate of major bleeding.

Consequences for my Practice

Bevyxxa® has not been studied in patients who have a DVT or PE and should not be used in such patients. However, it can be considered for 5-6 weeks for significantly immobile patients who are at high risk for a blood clot during and after a hospital admission for a severe acute medical illness.  As a hematologist, I am not much involved in the medical care of these patients.  The health care professionals who need to judge whether their elderly, sick patients who are discharged from the hospital should be on this drug are probably mostly hospitalists, congestive heart failure services, and those MDs who take care of these medically sick patients in the specific health care system the MD practices in.  Similarly, it is those MDs (with input from pharmacists and discharge planners) who should be involved in institutional algorithm/guideline development as to which patients are to be prescribed this treatment.

Reference

  1. Cohen AT et al. Extended Thromboprophylaxis with Betrixaban in Acutely Ill Medical Patients.  APEX Investigators. N Engl J Med. 2016 Aug 11;375(6):534-44.

 

Disclosure: Dr. Moll has consulted for Portola, Janssen, and Boehringer-Ingelheim.

Last updated:  July 6th, 2017