Archive for the ‘Warfarin (Coumadin)’ Category
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.
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 : 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.
Several studies on APS and the use of DOACs are ongoing, with details available 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)
We discuss with patient with APS who needs to be on an anticoagulant:
- … 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.
- … 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.
- 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… Apixaban (Eliquis®) was approved by the FDA this week (Aug 21, 2014) for the treatment of DVT and PE. The approval covers (a) acute DVT/PE management and (b) prevention of recurrent DVT/PE. Read the rest of this entry »
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.
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
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 »
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.
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
Stephan Moll, MD writes…
Occasionally, recurrent DVT or PE occur in spite of warfarin therapy, particularly in patients with (a) fluctuating and sub-therapeutic INRs, (b) lupus anticoagulant/ antiphospholipid antibody (APLA) syndrome or (c) cancer. Read the rest of this entry »
Stephan Moll writes…
2012 has been a year with significant progress in the field of venous thromboembolism and anticoagulation. The three most noteworthy, clinically relevant developments were probably (a) the publication of the new ACCP (American College of Chest Physician) guidelines on antithrombotic therapy in February 2012; (b) The FDA-approval of rivaroxaban (Xarelto) in November 2012 for the acute treatment of venous thromboembolism (VTE) and long-term secondary prevention; and (c) The FDA-approval of apixaban (Eliquis) in December 2012 for atrial fibrillation and the prevention of arterial thromboembolism. Here I have listed and summarized the 10 top publications of 2012 in the field of venous thromboembolism and anticoaguation as I see them – the ones clinically most relevant.
Disclosure: I have consulted for Janssen, Boehringer-Ingelheim and Daiichi.
Last updated: Feb 7th, 2013
Stephan Moll, MD writes… Well, it is not clear whether it does. A clinically relevant study (ASPIRE study) was published this week (Nov 22nd,2012) in the N Engl J Med [ref 1]. In patients who had a previous unprovoked (= idiopathic) DVT or PE and who had completed standard length (often considered to be 3-6 months) of warfarin therapy, aspirin did not prevent recurrent VTE. However aspirin was effective in preventing further thrombotic event (a conglomerate of arterial and venous events). Aspirin did not lead to an increase in risk of major bleeding. The findings are discrepant to the earlier WARFASA study, published in May 2012 in the N Engl J Med, which showed that Aspirin had efficacy in preventing recurrent VTE [ref 2]. The ASPIRE authors have also included a revealing, meta-analysis of this week’s study plus the previous WARFASA study [ref 2].
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 »