Effect of Dabigatran on Referrals to and Switching from Warfarin
Abstract & Commentary
By Harold L. Karpman, MD, FACC, FACP
Clinical Professor of Medicine, UCLA School of Medicine
Dr. Karpman reports no financial relationships relevant to this field of study.
Financial Disclosure: Internal Medicine Alert’s editor, Stephen Brunton, MD, serves on the advisory board for Abbott, Amarin, Boehringer Ingelheim, Duchesnay, Janssen, Lilly, Novo Nordisk, Sunovion, and Teva; he serves on the speakers bureau of Boehringer Ingelheim, Janssen, Lilly, Novo Nordisk, and Teva. Peer reviewer Gerald Roberts, MD; executive editor Leslie Coplin; and managing editor Neill Kimball report no financial relationships relevant to this field of study.
Synopsis: The frequency of initial prescriptions of dabigatran for stroke prevention in atrial fibrillation and the frequency
of transition from warfarin to dabigatran both proved
to be less than anticipated.
Source: Atay JK, et al. Effect of dabigatran on referrals to and switching from warfarin in two academic anticoagulation management services.
Am J Cardiol 2013;112:387-389.
Dabigatran has been demonstrated to decrease the rate of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (AF) by one-third, while also decreasing the rate of intracranial bleeding by two-thirds compared with warfarin.1 It is prescribed in a fixed dose (75-150 mg twice daily), is the first of several newer oral anticoagulants that may be administered without requiring laboratory coagulation monitoring, and has minimal drug-food and drug-drug interactions.2 On the basis of the ease of administration, equal or superior efficacy, and improved safety with respect to intracranial hemorrhage, it was anticipated that this new drug would replace warfarin for many patients.3
Atay and colleagues followed patients referred to two anticoagulation management services for stroke prevention in nonvalvular AF to determine how the rate of referral for warfarin management would be affected and how many existing patients would be switched from warfarin to dabigatran.4 The anticoagulation management service at Brigham and Women’s Hospital in Boston, Massachusetts (service 1) followed 1225 patients and a similar facility at the University of Michigan in Ann Arbor, Michigan (service 2) followed 1137 patients with nonvalvular AF. Only 81 patients (6.6%) from service 1 and 44 patients (3.9%) from service 2 switched from warfarin to dabigatran. The frequency of initial prescription of dabigatran for stroke prevention in AF as well as the frequency of transition from warfarin to dabigatran proved to be less than was expected.
The results of the data assembled by Atay et al should be carefully considered, but the limitations of the study are significant. It must be recognized that the patients did not come from office-based or community-based practices, but instead were referred from within university or teaching hospital environments, the period of observation was quite short, and the volume of patients was relatively small. The study focused only on dabigatran and did not include any of the other new anticoagulants such as rivaroxaban. Finally, the many reasons for slow adoption and cautious prescription of novel anticoagulants must be recognized. For example, the observed comparitive benefits of the newer anticoagulant agents would diminish when warfarin was well-managed.5 Also, there are concerns regarding the lack of specific reversal agents for the newer anticoagulants. Concerns also initially existed regarding an increase in cerebral bleeding episodes when taking the newer agents compared with what would be expected with warfarin, although the FDA recently indicated that bleeding rates associated with dabigatran did not appear to be higher than the bleeding rates associated with warfarin use.5 Furthermore, since medication adherence rates for patients with chronic disease states are extremely low,7 in the range of 43-78%, and without the regular prothrombin time management needed for patients on warfarin therapy, physicians have no way of assessing whether the patients are really taking the newer anticoagulants as prescribed. Finally, it should be recognized that dabigatran has a much shorter half-life than warfarin and, therefore, a missed dose of the newer agents will leave the patient unprotected from stroke risk.
Obviously, it’s much more convenient for AF patients to use one of the newer anticoagulant agents. However, for the many reasons outlined above, patients should be carefully selected and fully informed on how important it is for them to take their medications regularly as prescribed. As more data become available from the use of these novel agents in office-based patients from the several large observational studies that are now in progress, it is very likely that warfarin use will decrease, despite the limitations of the newer anticoagulant agents outlined above and the increased cost of these newer agents which, incidentally, will probably diminish as more of them become available.
- Connolly SJ, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009;361: 1139-1151.
- Garcia D, et al. The new oral anticoagulants. Blood 2010;115:15-20.
- Schwartz NE, et al. Dabigatran challenges warfarin’s superiority for stroke protection in atrial fibrillation. Stroke 2010;41:1307-1309.
- Atay JK, et al. Effect of dabigatran on referrals to and switching from warfarin in two academic anticoagulation management services. Am J Cardiol 2013;112:387-389.
- United States Food and Drug Administration. Pradaxa (dabigatran etexilate mesylate): Drug Safety Communication — Safety Review of Post-Market Reports of Serious Bleeding Events. Available at: http://www.fda.gov/safety/medwatch/safetyinformation/safetyalertsforhumanmedicalproducts/ucm282820.htm. Accessed
on September 18, 2013.
- Eerenberg ES, et al. Reversal of rivaroxaban and dabigatran by prothrombin complex concentrate. Circulation 2011;124:1573-1579.
- Osterberg L, et al. Adherence to medication. N Engl J Med 2005;353:487-497.