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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

ACCP Guideline for DVT and PE Treatment: New Edition, 2016

| Anticoagulants, Aspirin, Plavix, Aggrenox, Tiklid, Persantine, Edoxaban, Eliquis, Guideline, Pradaxa (dabigatran), Therapy, Uncategorized, Xarelto (Rivaroxaban) | Comments Off on ACCP Guideline for DVT and PE Treatment: New Edition, 2016

The ACCP Chest Guidelines have been the main guide over the last more than 2 decades for evidence-based recommendations on best management of anticoagulants for various indications, including DVT and PE.  The 10th edition of the chapter on DVT and PE management was published in Jan 2016 [ref 1]. Unfortunately, the guideline is not available for non-subscribers. Read the rest of this entry »

Fourth NOAC FDA Approved for DVT, PE and Atrial Fibrillation: Savaysa (Edoxaban)

| Edoxaban, Eliquis, Pradaxa (dabigatran), Uncategorized, Xarelto (Rivaroxaban) | Comments Off on Fourth NOAC FDA Approved for DVT, PE and Atrial Fibrillation: Savaysa (Edoxaban)

Stephan Moll, MD writes…. Today (Jan 8th, 2015) the FDA approved yet another new oral anticoagulant, Savaysa (edoxaban), for the treatment of DVT and PE, as well as for atrial fibrillation. The FDA press release  is here (link).  Savaysa is the 4th of the NOACS now approved for VTE treatment. This table summarizes the differences, advantages and disadvantages comparing the 4 drugs. The detailed drug package insert with dosing information is here (link). Read the rest of this entry »

Antidotes for the New Oral Anticoagulants: Update

| Anticoagulants, Bleeding, Eliquis, Pradaxa (dabigatran), Uncategorized, Xarelto (Rivaroxaban) | Comments Off on Antidotes for the New Oral Anticoagulants: Update

Stephan Moll, MD writes (on Nov 7th, 2014)… A N Engl J Med publication this week [ref 1] reports on a new reversal agent (PER977 = Aripazine = ciraparantag) that may be effective against a number of different new oral anticoagulants. Read the rest of this entry »

Pradaxa (Dabigatran) FDA-Approved for DVT and PE

| Eliquis, Pradaxa (dabigatran), Therapy, Uncategorized, Xarelto (Rivaroxaban) | Comments Off on Pradaxa (Dabigatran) FDA-Approved for DVT and PE

Stephan Moll, MD writes…  Today the FDA approved Pradaxa (dabigatran) for the treatment of venous thromboembolism, based on the phase 3 RECOVER and RECOVER II trials.  The dose is 150 mg twice daily for patients with a GFR > 30 ml/min.  Due to the design of the RECOVER and RECOVER II trials, the drug is approved to be used in the patient with acute DVT or PE only AFTER 5-10 days of a parenteral anticoagulant have been given –  not immediately from day zero onwards.   The full package insert is here.  The press release from Boehringer-Ingelheim is here.   The FDA approval status of the four big new oral anticoagulants for the various indications is summarized  in this table.

 

Disclosures:  I have been a consultant for Boehringer-Ingelheim,  Daiichi, and Janssen.

Last updated:  April 7th, 2014

Pregnancy, Breastfeeding – Safety of Various Anticoagulants

| Anticoagulants, Eliquis, Fondaparinux (Arixtra), LMWH, Pradaxa (dabigatran), Uncategorized, Warfarin (Coumadin), Xarelto (Rivaroxaban) | Comments Off on Pregnancy, Breastfeeding – Safety of Various Anticoagulants

Stephan Moll, MD writes… LMWH (low molecular weight heparin) is the preferred anticoagulant in the pregnant patient. LMWH and warfarin are safe in the woman who is beast-feeding.

Rivaroxaban (Xarelto), dabigatran (Pradaxa) and apixaban (Eliquis) should not be used during pregnancy or while breastfeeding.

A detailed summary about the safety of the various anticoagulants during pregnancy and while breast-feeding, based on the ACCP 2012 guidelines [ref], can be found here.  Read the rest of this entry »

FDA to Review Eliquis (Apixaban) for DVT and PE Treatment

| Anticoagulants, Eliquis, Pradaxa (dabigatran), Uncategorized, Xarelto (Rivaroxaban) | Comments Off on FDA to Review Eliquis (Apixaban) for DVT and PE Treatment

Stephan Moll, MD writes… On Dec 19th the FDA accepted the application by Bristol-Myers Squibb (BMS) and Pfizer for review of Eliquis (apixaban) for the treatment of DVT and PE. The press release of BMS is here.  The goal date for a decision by the FDA is August 25, 2014. Read the rest of this entry »

Handout for Your Patients in Clinic – Which Anticoagulant to Use for DVT and PE

| Anticoagulants, Deep Vein Thrombosis (DVT), Eliquis, Pradaxa (dabigatran), Pulmonary Embolism, Uncategorized, Warfarin (Coumadin), Xarelto (Rivaroxaban) | Comments Off on Handout for Your Patients in Clinic – Which Anticoagulant to Use for DVT and PE

Stephan Moll, MD writes…  Patients who are on warfarin for a history of DVT or PE  may inquire whether a switch to one of the  new oral anticoagulants is appropriate.  Similarly, many physicians initiate this discussion with their patients.

This is, obviously, a detailed discussion and an individualized decision with a number of factors to be considered.  We have developed a two-page “Comparison of Oral Blood Thinners”  handout for patients, to assist with and summarize the discussion.  This sheet allows a structured  discussion with the patient about the pros and cons of the various anticoagulant choices.  The reader is welcome to print this resource and use it as a handout for his/her patients.

Disclosure:  I have been a consultant for  Boehringer-Ingelheim, Daiichi, and Janssen.

Last Updated:  Dec 19th, 2013

Major Bleeding on Dabigatran (Pradaxa) – Interesting Publication

| Anticoagulants, Bleeding, Pradaxa (dabigatran), Therapy, Uncategorized | Comments Off on Major Bleeding on Dabigatran (Pradaxa) – Interesting Publication

Stephan Moll, MD writes…

Interesting publication this week in Circulation: “Management and outcomes of major bleeding during treatment with dabigatran or warfarin” (Majeed A et al; published online Sept 30,2013;  full publication is here).  The management and prognosis of major bleeding in patients treated with dabigatran or warfarin was compared, pooling data of the major bleeds that occurred in 5 phase III dabigatran trials. 1,121 major bleeds occurred in 27,419 patients treated with warfarin or dabigatran.

 

The noteworthy findings: 

  1. Patients with major bleeding on dabigatran (Pradaxa) do not fare worse than patients with major bleed on warfarin (regarding 30 day mortality). They may actually fare a little better, as evidence by a shorter stay in the intensive care unit.  That is reassuring when discussing the choice of the anticoagulant (warfarin versus dabigatran) with a patient.
  2. There were (as we already knew from previous publications) significantly less intracranial bleeds on dabigatran than on warfarin; however, there were more GI bleeds on dabigatran (supplemental table 1). This is noteworthy, as many would view an intracranial bleed as more worrisome and detrimental than a gastrointestinal bleed.
  3. Warfarin reversal is done suboptimally in clinical practice: In patients with major bleeding on warfarin, (i) only 30 % of patients received vitamin K and (ii) only 1.2 % of patients received a prothrombin complex concentrate (PCC); 30 % received FFP.  This is noteworthy, as guidelines (ACCP 2012) suggest that in case of major bleeding on warfarin PCCs be given rather than plasma (FFP); and vitamin K should be standard of care in warfarin reversal.  The observation in this Circulation publication reflects that reversal of warfarin therapy is often suboptimally done, even though  appropriate tools exist, i.e. vitamin K and PCCs  (see also Clot Connect’s Kcentra discussion here).

 

Disclosure:  I have consulted for Boehringer-Ingelheim.

Last updated:  Oct 2nd, 2013