Beth Waldron, Clot Connect Program Director writes….
The physical consequences of thromboembolism (VTE) [=deep vein thrombosis DVT and pulmonary embolism PE] have been extensively reported in the medical literature. Less documented has been the emotional impact of VTE on patients. This lack of formal study is notable given the extensive research on the psychological impact of other sudden, potentially life-threatening cardiovascular events (heart attack, stroke) which has provided clear evidence that such illnesses can result in significant psychological morbidity and contribute to adverse health outcomes. Read the rest of this entry »
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
Stephan Moll, MD writes… A recent NEJM study (ref 1) examined whether the risk for thrombosis in women persists beyond the first 6 weeks after delivery. It found that an increased risk persists for at least 3 months after delivery, although the absolute risk was low after the first 6 weeks. This is of clinical relevance, as the post-partum period has traditionally often been defined as the 6 weeks after delivery and, if post-partum anticoagulation prophylaxis is considered, it is typically given for 6 weeks only (ACOG – ref 2). Read the rest of this entry »
Stephan Moll, MD writes… This week (Feb 18th, 2014) a guidance document on the prevention and management of catheter-associated upper extremity (brachial, axillary, subclavian, and brachiocephalic veins) and neck (internal jugular) DVT was published by the International Society for Thrombosis and Haemostasis (ISTH) [ref 1]. The authors acknowledge that optimal long-term management of catheter-associated DVT has not been established. The key recommendations: Read the rest of this entry »
Stephan Moll, MD writes… No reversal agent (antidote, neutralizing drug) is presently clinically available if (a) major bleeding occurs or (b) urgent reversal for emergent surgery is needed in patients on one of the new oral anticoagulants (apixaban = Eliquis; dabigatran = Pradaxa; edoxaban = Savaysa; rivaroxaban = Xarelto). At least three drugs are in development, but all are at least 2 years away from being clinically available, should they prove to be beneficial.
- ANDEXANET (PRT064445)
- What is it? Recombinant, modified factor Xa molecule that is being developed as a direct reversal agent (antidote) for patients receiving a Factor Xa inhibitor who suffer a major bleeding episode or who require emergency surgery. It sort-of sops up the anti-Xa anticoagulant, making a patients own factor Xa available again to participate in the coagulation process.
- What anticoagulant drugs might it reverse? Apixaban, edoxaban, rivaroxaban.
- Clinical trial status: A phase 2 healthy volunteer study is ongoing to evaluate the ability of Andexanet to reverse the effects of several anticoagulant drugs on laboratory tests (NCT01758432).
- What is it? It is a humanized antibody fragment directed against dabigatran; generated from mouse monoclonal antibody against dabigatran; humanized and reduced to a FAb fragment.
- What anticoagulant drugs might it reverse? Dabigatran.
- Clinical trial status: (a) A phase 3 study of patients on dabigatran with major bleeding or needing emergency surgery is in the planning stages and will likely start in 2014. (b) A phase 1 study to determine the effect of idarucizumab on coagulation tests in dabigatran-treated healthy volunteers has been completed (NCT01688830), another two are ongoing (NCT01955720; NCT02028780).
- What is it? This is a synthetic small molecule (D-arginine compound) which appears to have broad activity against various new oral anticoagulants (dabigatran, rivaroxaban, apixaban and edoxaban) and other anticoagulants (heparins).
- What anticoagulant drugs might it reverse? Apixaban, edoxaban, rivaroxaban, dabigatran, heparin, LMWH.
- Clinical trial status: This drug has not yet been used in humans. It has been shown to have activity in rat bleeding models [Laulicht B et al. Small molecule antidote for anticoagulants [abstract];Circulation 2012; 126:A11395].
Conflict of interest: None.
Last updated: Feb 20th, 2014
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… 2014 promises to be quite a year regarding the new oral anticoagulants. On Jan 8th, 2013 the company Daiichi applied for FDA approval for their drug edoxaban (Savaysa®) for 2 indications: (a) DVT and PE (venous thromboembolism; VTE) treatment, and (b) non-valvular atrial fibrillation and the prevention of systemic arterial thromboembolism. This application is based on the 2 large phase 3 edoxaban trials, one in VTE, one in A. fib, both published in the New England Journal of Medicine in 2013 [ref 1,2].
Here is a summary of the FDA approval status and application status of the 4 big new oral anticoagulants. Also On Jan 8th, 2014, the brand name of edoxaban was announced: Savaysa (Daiichi press release here).
- The Hokusai-VTE Investigators. Edoxaban versus warfarin for the treatment of symptomatic venous thrmomboembolism. N Engl J Med 2013;369:1406-1415 (Oct 10, 2013).
- Giugliano RP et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2013;369(22):2093-104(Nov 28, 2013).
Disclosure: I have consulted for Janssen, Daiichi, and Boehringer Ingelheim.
Last updated: March 14th, 2013
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 »
Stephan Moll, MD writes… The annual meeting of the American Society of Hematology (ASH) took place this month (Dec 6-12th, 2013) in New Orleans. The clinically relevant highlights about thrombosis and anticoagulation are summarized below. Read the rest of this entry »
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