Archive for the ‘Therapy’ 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… 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 drug in clinical trials as an antidote to reverse the blood thinning effect of Eliquis®, Savaysa®, Xarelto® 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 (enoxaparin) 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 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 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]. Read the rest of this entry »
Stephan Moll, MD writes… Interesting and relevant publication this week [reference 1]. It is well known that estrogen–containing birth control methods (pills, vaginal rings, patches, injectables) increase the risk for DVT and PE. As women on blood thinners may have heavy menstrual bleeds, hormonal therapy may be considered to decrease the bleeding. Also, women on blood thinners may want to choose a method for contraception other than a progestin IUD (Mirena® IUD, Skyla® IUD).
The newly published study Read the rest of this entry »
Stephan Moll, MD writes… An article for patients discussing (a) IVC filters (inferior vena cava filters; also often referred to as “Greenfield filters”), (b) narrowing of the main left pelvic vein (referred to as May-Thurner syndrome) and (c) stents in veins in the pelvis has just been published (http://circ.ahajournals.org/content/133/6/e383.full.pdf). Color images are included helping explain what these conditions are.
Reference: Carroll S, Moll S. Circulation. 2016;133:e383-e387
Last updated: Feb 18th, 2016
Stephan Moll, MD writes… A new consensus guidance for health care professionals on management of DVT and PE – link here – was published today, Jan 18th, 2016, in the Journal of Thrombosis and Thrombolysis. The publication contains 13 chapters on various aspects of DVT and PE (acute treatment, decisions on length of blood thinner treatment, thrombophilia work-up, management at times of surgery, etc.). It incorporates both evidence-based data and consensus opinion of the 52 international experts who wrote these chapters. It is aimed at any type of health care professional who is involved in the management of DVT and PE – emergency room physicians, hospitalists, internists, cardiologists, hematologists, pharmacists and others.
Last updated: Jan 18th, 2016
Stephan Moll, MD writes… In general: “Yes”. Many people who take blood thinners are able to safely dive. However, there are a few things to consider for the individual on blood thinners who wants to go scuba diving: Read the rest of this entry »
Stephan Moll, MD writes: A drug in development (Idarucizumab) that reverses the blood thinner Pradaxa® (Dabigatran) is on a very promising path to get FDA approval in the next few months and be available for clinical use by the end of 2015.
Read the rest of this entry »
Stephan Moll, MD writes…. Today (Jan 8th, 2015) the FDA approved yet another new oral blood thinner, Savaysa (edoxaban), for the treatment of DVT and PE. The drug was also FDA approved today for stroke prevention in patients with irregular heart beat (atrial fibrillation). The FDA press release here (link). Read the rest of this entry »
Stephan Moll, MD writes (Dec 17, 2014)… The American Society of Hematology (ASH) published last week two things that physicians dealing with DVT, PE and blood thinners should avoid [ref 1]. Read the rest of this entry »