Response to Letters Regarding Article, “Using Dabigatran in Patients With Stroke: A Practical Guide for Clinicians”
We appreciate the thoughtful comments and important issues raised by the letters published.
As Casado-Nananjo et al highlight, there are anecdotal case reports of intravenous tissue-type plasminogen activator (tPA) for acute ischemic stroke being used without complications in patients treated with dabigatran as well as with catastrophic consequences in such settings. These reports often lack data about the timing of the last dose of dabigatran, renal function, and other important variables. One should remember that dabigatran is a potent anticoagulant, and tPA is a powerful lytic agent. There have been studies suggesting that a clot formed in patients taking dabigatran may be more susceptible to complete lysis when using tPA, but this might also be associated with higher rates of hemorrhage.1
Freeman and colleagues present a single case of successful endovascular therapy in a patient with a potentially large middle cerebral artery territory stroke that occurred shortly after dabigatran therapy was restarted. Although an endovascular approach limits the issues related to the systemic use of tPA, there was still evidence of a dabigatran-related anticoagulant effect, as seen by the elevated thrombin time. Fortunately, this patient did very well.
At this time, there is a paucity of data about using intravenous tPA or acute endovascular approaches in patients receiving dabigatran. Some hospitals have developed various treatment protocols based on the time of the last dabigatran dose, renal function, coagulation test results, stroke size, and other variables. A major concern is that with both agents in the treatment milieu, any bleeding events are likely to be major if not catastrophic. It should also be noted that the current Alteplase package insert has “current use of oral anticoagulants” as a contraindication.
With respect to the issue of mechanical valves, we agree with Van de Werf et al about the lack of convincing data for using dabigatran in such circumstances. There are several ongoing studies that have shown at least partial success for dabigatran in preventing or reducing clot formation in several in vitro and in vivo mechanical valve models.2,3 Also, the therapeutic international normalized range for using warfarin in the setting of a mechanical valve is 2.5 to 3.5, which partially overlaps the target international normalized range (2.0–3.0) used in the Randomized Evaluation of Long-Term Therapy (RE-LY) study. Thus, the dose of dabigatran used in RE-LY may be close to the range that may be effective for thromboprophylaxis with mechanical valves. Of course such patients were excluded from RE-LY.
We agree that the plural of anecdote is not data. Although we may get solid data based on clinical trials about the use of dabigatran in patients with mechanical valves, it appears unlikely any high-quality data on the issue of intravenous tPA and/or endovascular therapy for acute ischemic stroke in patients taking dabigatran will be forthcoming. Treating patients anecdote by anecdote is unsatisfying and potentially misleading. Perhaps a registry of such cases might be helpful, but only if selective enrollment can be limited to ensure representative results.
Mark J. Alberts, MD
Richard A. Bernstein, MD, PhD
Gerald V. Naccarelli, MD
Pennsylvania State University
University Park, PA
David A. Garcia, MD
University of New Mexico
M.J.A. has received speaking honoraria from Boehringer-Ingelheim and Genentech, Bristol-Myers Squibb, and Sanofi-Aventis, and is a consultant for Janssen, Merck, Bristol Myers Squibb, Sanofi-Aventis, Genentech, Pfizer and Lundbeck. He has received research funding from Merck and serves on an adjudication committee for Lundbeck. R.A.B. has received speaking and/or consulting honoraria from Boehringer-Ingleheim, Sanofi, and Ortho-McNeil-Janssen and research support from Bristol Myers Squibb, Pfizer, Lifewatch, and Medtronic. G.V.N. has received research support from Boehringer-Ingelheim and is a consultant for Pfizer, Bristol-Myers Squibb, Boehringer-Ingelheim, Portola, and Ortho-McNeil-Janssen. D.A.G. has received research funding from Bristol Myers and Boehringer Ingelheim and is a consultant for Bristol Myers, Boehringer-Ingleheim, OrthoMcNeil, and Daichii Sankyo.
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- © 2012 American Heart Association, Inc.
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