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Posts Tagged ‘Warfarin’

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

Reversing Warfarin for Urgent Surgeries – Extended FDA Approval of Kcentra

| Uncategorized, Warfarin (Coumadin) | Comments Off on Reversing Warfarin for Urgent Surgeries – Extended FDA Approval of Kcentra

Stephan Moll, MD writes… The FDA approved today (Dec 13th, 2013) the use of the drug Kcentra® for urgent warfarin reversal in patients who need an urgent surgical procedure.  This extends the indications for use of this drug – it had been approved by the FDA in April 2013 to treat major bleeding on warfarin [ref 1]. Read the rest of this entry »

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

International Coagulation Meeting (ISTH 2013): Highlights

| Anticoagulants, Deep Vein Thrombosis (DVT), Eliquis, Inherited, Pradaxa (dabigatran), Pulmonary Embolism, Therapy, Thrombophilias, Uncategorized, Xarelto (Rivaroxaban) | Comments Off on International Coagulation Meeting (ISTH 2013): Highlights

Stephan Moll, MD writes…  A major international coagulation conference, the bi-annual meeting of the International Society for Thrombosis and Haemostasis (ISTH; www.isth.org), took place in Amsterdam, Holland, from June 29th to July 4th, 2013.  The clinically relevant highlights about thrombosis and anticoagulation are summarized below. Read the rest of this entry »

FDA Approval of New Drug to Treat Major Bleeding on Warfarin – Kcentra

| Anticoagulants, Bleeding, Uncategorized, Warfarin (Coumadin) | Comments Off on FDA Approval of New Drug to Treat Major Bleeding on Warfarin – Kcentra

Stephan Moll, MD writes…  A new drug for the urgent reversal of warfarin was approved by the FDA today, April 29th, 2013 (announcement by the FDA is here), called Kcentra.  The drug is derived from pooled plasma from healthy blood donors and contains the coagulation factors that are low in warfarin-treated patients, i.e. factors II, VII, IX, and X.  It is also referred to as a 4-factor concentrate, or non-activated Prothrombin Complex Concentrate (PCC).  The drug prescribing information (package insert) is here.

Up until now only 3-factor concentrates (PCC) and fresh frozen plasma (FFP) were available in the U.S. in addition to vitamin K to urgently reverse warfarin and to treat major bleeding in warfarin-treated patients.  The new drug is a welcome addition to the armamentarium when having to treat warfarin-associated major bleeding.  Where until now I used to give 3-factor PCCs, I will now give the 4-factor PCC.

 

Bleeding and the new oral anticoagulants

A question that will now be raised is whether this new drug is also suitable to treat major bleeding on one of the new oral anticoagulants, i.e. Xarelto, Pradaxa, or Eliquis.  It is not known whether Kcentra would be beneficial in that situation.  However, as some hospitals and clinicians presently have 3-factor PCCs on their reversal algorithm, it is fair to consider a review and possible modification of the hospital treatment guidelines on the management of major bleeding not only on warfarin, but also on the new oral anticoagulants.

 

 Reference

Sarode R et al. Efficacy and safety of a 4-factor prothrombin complex concentrate in patients on vitamin K antagonists presenting with major bleeding. A randomized, plasma-controlled, phase IIIb study. Circulation 2013;128:1234-1243.

 

Disclosure: I have consulted for CSL Behring, the comapny making Kcentra.

Last updated: Dec 13th, 2013

 

 

 

 

 

Aspirin Prevents Recurrent DVT and PE – WARFASA Study

| Anticoagulants, Aspirin, Plavix, Aggrenox, Tiklid, Persantine, Therapy, Uncategorized | Comments Off on Aspirin Prevents Recurrent DVT and PE – WARFASA Study

Stephan Moll, MD writes… A clinically very relevant study (WARFASA) published today (May 24, 2012) in the New England Journal of Medicine [ref 1] shows that aspirin, 100 mg per day, reduces the risk of recurrent venous thromboembolism (VTE) in patients with unprovoked (= idiopathic) VTE, who have completed 6 to 18 months of anticoagulant therapy, without an apparent increase in risk of major bleeding Read the rest of this entry »

INR Self-Testing

| Uncategorized, Warfarin (Coumadin) | Comments Off on INR Self-Testing

Stephan Moll, MD writes…

A detailed, practical discussion on INR self-testing for patients is available here, addressing:

  • Reasons to do INR self-testing
  • Which patients are suitable
  • What INR home monitoring devices are available
  • Whether the devices give reliable INR results
  • Whether insurance companies pay for them Read the rest of this entry »