After a lengthy delay, the US Food and Drug Administration (FDA) cleared apixaban (Eliquis®, Bristol-Myers Squibb/Pfizer) for prevention of stroke in non-valvular atrial fibrillation on 12.28.12. Apixaban is an oral direct anti-Xa anticoagulant and joins rivaroxaban and dabigatran (a direct thrombin inhibitor) as the third new oral anticoagulant cleared since 2009. Details appear in TheHeart.org.
In 2009 Dave McGlasson and I published McGlasson DL, Fritsma GA, Whole blood platelet aggregometry and platelet function testing. Semin Thromb Hemost 2009;35:168–80. This article, the second-most cited in the 2009 Seminars in Thrombosis and Hemostasis, reminded me of our Quick Question about the Ivy bleeding time posted in early November, and subsequently lost when our site crashed in late November. While my goal in posting the Quick Question was to reemphasize the futility of the bleeding time, my research led me to a lengthy and engrossing article by medical historian Dr. Patricia Spain Ward, 1931–1995, “Who Will Bell the Cat? Andrew C. Ivy and Krebiozen.” The article was developed from a speech given by Dr. Ward at the Morris Fishbein Center for the Study of the History of Science and Medicine, University of Chicago on April 8, 1983 and published in the Bulletin of the History of Medicine 1984;58:28–52. I’ve prepared a brief summary of the bleeding time test, attached, Ivy’s role in its development, and his subsequent fall from grace when he promoted a false cancer cure. The “Bell the Cat” phrase refers to Aesop’s fable in which a group of mice held a meeting to decide how to prevent the cat from sneaking up on them. One mouse suggests they tie a bell to the cat, and all the others rejoice at the solution until a wise elder rose to ask, “Who will bell the cat?” No one was able to tie the bell to Ivy. To read, please click on AC Ivy Story.
In a plenary session on Sunday, December 9, 2012, Dr. Simon Stanworth reported on a trial of 600 patients being treated for hematologic malignancies, chemotherapy, or stem cell transplants, Stanworth SJ, Estcourt L, Powter G, et al. The effect of a no-prophylactic versus prophylactic platelet transfusion strategy on bleeding in patients with hematological malignancies and severe thrombocytopenia (TOPPS trial). A randomized controlled, non-Inferiority trial. In the US, just over two million units of platelet concentrate are given per year at an approximate cost of $1000 per unit. About 2/3 are given prophylactically, 1/3 are used to treat current bleeding. Half of the no-prophylaxis arm experienced no bleeding, compared to 43% of the prophylaxis arm, indicating that many patients are transfused unnecessarily. New trials that provide risk stratification will be coming next.
On 12.20.12, the US Food and Drug Administration warned that dabigatran should not be used to prevent stroke in patients with mechanical heart valves. The FDA’s announcement was preceded by a Boehringer Ingelheim press release detailing the contraindication. Here is Boehringer’s new statement: “The safety and efficacy of PRADAXA in patients with bileaflet mechanical prosthetic heart valves (recently implanted or implanted more than 3 months prior to enrollment) was evaluated in the phase 2 RE-ALIGN trial. RE-ALIGN was terminated early because of significantly more thromboembolic events (valve thrombosis, stroke, transient ischemic attack, and myocardial infarction) and an excess of major bleeding (predominantly post-operative pericardial effusions requiring intervention for hemodynamic compromise) for PRADAXA vs warfarin. Therefore, the use of PRADAXA is contraindicated in patients with mechanical prosthetic valves.”
According the results of a randomized control trial involving almost 2500 patients reported in the New England Journal of Medicine, twelve months of treatment with apixaban (Eliquis, Bristol-Myers Squibb/Pfizer) at either of two dosages, given after six to 12 months of anticoagulation to treat venous thromboembolism (VTE), significantly lowered the risk of recurrent VTE compared with placebo. See the NEJM article below.
Dr Sam Schulman of McMaster University reported on a meta-analysis, Majeed A, Hwang HG, Brueckmann M, et al. Management and outcomes of major bleeding on dabigatran or warfarin, at the American Society of Hematology annual meeting on Saturday, December 8, 2012. They found that, “The prognosis after a major bleed on dabigatran was, despite lack of a specific antidote, better than with warfarin. There was also a shorter stay in intensive care with dabigatran compared to warfarin.” Their findings appear to contradict claims made in numerous lawsuits against manufacturer Boehringer Ingelheim.
Here is a link to the latest EINSTEIN findings comparing rivaroxaban with enoxaparin for treatment of deep venous thrombosis (DVT) and pulmonary embolism (PE) reported Dr. Harry Buller at the American Society for Hematology meeting on 12.11.12 in Atlanta, Georgia.
Click here to see the Anticoagulation Forum December newsletter with information on the Forum’s annual meeting in Phoenix, May 9–11 and their new Centers of Excellence web site. There is also a review describing recent studies that illustrate no effect of cranberry products on Coumadin therapy.