Archive for the ‘Anticoagulants’ Category
Stephan Moll, MD and Damon Houghton, MD write … Antiphospholipid syndrome (APS) is an acquired clotting disorder. Patients with APS may have DVT or PE that requires treatment with blood thinners. Warfarin (Coumadin®, Jantoven®), and sometimes the injectable heparin drugs (enoxaparin = Lovenox®; dalteparin = Fragmin®; tinzaparin = Innohep®; etc.), have traditionally been used in patients with APS. A question that comes up is whether one of the new oral blood thinners (apixaban = Eliquis®; dabigatran = Pradaxa®; edoxaban = Savaysa®; rivaroxaban = Xarelto®) can be used instead of warfarin or a heparin drug. These drugs are collectively referred to as direct oral anticoagulants (DOACs).
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.
Multiple cases of patients with APS treated with a DOAC have been published. All of these (i.e. a total of 122 patients) have recently been summarized [ref 1]: Sixteen percent (i.e. one of every 6 patients) had a recurrent clot on a DOAC. As this is a high rate of DOAC failure, the authors caution about the use of DOACs in APS. However, two things need to be considered: (a) it is also known that warfarin has a high failure rate [references 2,3]; and (b) due to the nature of case report publications (potential bias; absence of control group), no strong or meaningful conclusion is really possible as to how DOACs compare to warfarin in the treatment of DVT and PE in patients with APS
Several studies on APS and the use of DOACs are ongoing. Details of the following studies can be found at clinicaltrials.gov:
- NCT02157272: A Prospective, Randomized Clinical Trial Comparing Rivaroxaban with Warfarin in High Risk Patients With Antiphospholipid Syndrome (TRAPS)
- NCT02295475: Apixaban for the Secondary Prevention of Thromboembolism Among Patients With the AntiphosPholipid Syndrome (ASTRO-APS)
- NCT02116036: Rivaroxaban for Antiphospholipid Antibody Syndrome (RAPS)
This is what we discuss with the patient with APS who needs to be on a blood thinner:
- I highlight 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.
- I discuss the fact 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 to use a twice daily dosed blood thinner (Eliquis® or Pradaxa®) rather than a once daily dosed drug (Xarelto® or Savaysa®). The thought behind this is that a twice daily dosed drug leads to more steady drug levels throughout the day and that this may lead to a more effective blood thinning effect. However, this is a theory unproven, and whether this truly leads to a lower risk of recurrent clots than being on a once daily drug is not known. A recent publication of a case report with discussion of drug metabolism also favors a twice daily rather than a once daily dosed drug in patients with APS [ref 4]. Ultimately, the most effective medication is likely the one that is taken as prescribed; therefore, a patient’s preference regarding the feasibility and practicality of a once daily versus twice daily medication is also an important consideration.
- 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.
- 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.
- 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.
- 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
Stephan Moll, MD writes… Today, June 23, 2017, the FDA approved a 5th new oral blood thinner for clinical use, Bevyxxa® (= Betrixaban), taken once daily. It is FDA approved to prevent blood clots (DVT and PE) for patients who are significantly immobile and, therefore, at increased risk for blood clots during and after hospitalization for an acute medical illness. Full prescribing information: here. FDA details: here.
In the study that led to FDA approval (APEX study; 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. Fewer blood clots happened in the patients treated with the drug, without an increase in 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.
- 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: June 25th, 2017