Archive for the ‘Therapy’ 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… 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.
- 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
Stephan Moll, MD writes… The FDA did NOT approve Andexanet (brand names: AndexXa™ in the US, IndexXa™ in Europe) in a decision on August 18th, 2016. Andexanet is the antidote in clinical development to reverse the anticoagulant effect of Eliquis® (rivaroxaban), Savaysa® (edoxaban), Xarelto® (rivaroxaban) and Lovenox® (enoxaparin). The FDA is said to have requested more information from the company (Portola) making Andexanet, specifically (a) additional information related to manufacturing of the drug, and (b) more data to support inclusion of Savaysa® and Lovenox® in the label. The FDA also wants to finalize its review of the company’s proposals for post-marketing data collection on the performance of the drug.
It needs to be seen when the company (Portola) submits the requested additional information to the FDA and when a new decision from the FDA is then to be expected. My guess is that this will be sometime in 2017.
- Portola announcement from Aug 18, 2016: http://bit.ly/2c1wKaK
- Connolly SJ et al. Andexanet alfa for acute major bleeding associated with factor Xa inhibitors. NEJM 2016;Aug 30 [e-pub]
Disclosure: I have consulted for Portola, Janssen, and Boehringer-Ingelheim.
Last updated: Aug 31st, 2016
Stephan Moll, MD writes… Interesting and noteworthy observations published in the last 2 weeks: Heavy menstrual bleeding appears to occur more commonly with Xarelto® than with warfarin [ref 1] and may be also more common with Xarelto® than with Eliquis® [ref 2].
Stephan Moll, MD writes… Interesting and clinically relevant publication this week [ref 1]. It is well known that estrogens and certain progestin preparations increase the risk for venous thromboembolism (VTE). A woman on an anticoagulant may have heavy menstrual bleeds and hormonal therapy – such as estrogen-progestin contraceptives – may be considered to decrease the bleeding.
The newly published study Read the rest of this entry »
Stephan Moll, MD writes… Our medical center (University of North Carolina Hospitals, Chapel Hill) has put together a comprehensive “Emergent Anticoagulation Reversal Guideline” for our local use, updated since its last edition in 2014 with information about Pradaxa® reversal (with Praxbind®). It is a practical, clinical how-to document (2016 PDF here ). Colleagues and hospitals are welcome to take the document, modify it, and apply it to their institution – there are no copyright concerns.
Disclosures: I have been a consultant on one occasion for Boehringer-Ingelheim.
Last updated: May 11th, 2016
Stephan Moll, MD writes… An article for patients discussing (a) IVC filters, (b) narrowing of the main left pelvic vein (May-Thurner syndrome) and (c) pelvic venous stents has just been published (http://circ.ahajournals.org/content/133/6/e383.full.pdf). Color images of anatomy, filters and stents are included as visual aids. The article may be helpful as handout material for patients in clinic.
Reference: Carroll S, Moll S. Circulation. 2016;133:e383-e387
Last updated: Feb 18th, 2016
Stephan Moll, MD writes… A new consensus guidance on management of venous thromboembolism (VTE) – link here – was published today, Jan 18th, 2016, in the Journal of Thrombosis and Thrombolysis. The publication contains 13 chapters on various aspects of VTE Read the rest of this entry »
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 »
Stephan Moll, MD writes… Can patients on anticoagulants safely scuba dive? In general: “Yes”. Many people who take anticoagulants are able to safely dive. However, there are a few things to consider: Read the rest of this entry »