Author + information
- Stijn P.G. van Vugt, MD∗ (, )
- Marc A. Brouwer, MD, PhD and
- Freek W.A. Verheugt, MD, PhD
- ↵∗Radboud University Medical Center, Department of Cardiology, Geert Grooteplein 10, Route 616, P.O. Box 9101, 6500 HB Nijmegen, the Netherlands
In their report, Steinberg et al. (1) nicely demonstrate that despite the advantage of uniform non-vitamin K antagonist oral anticoagulants (NOAC) dosing, off-label treatment occurs in approximately 13% of patients, which is related to adverse outcomes.
Most of these cases concerned underdosing. In the event of a high anticipated risk of bleeding, we strongly advise against underdosing and recommend choosing a NOAC that has a superior safety profile compared with a vitamin K antagonist (VKA), prescribed in the appropriate dose. Inadvertent dosing of NOACs may also occur because of the nonuniform criteria for dose reduction. For example, a glomerular filtration rate <50 ml/min is the sole criterion for dose reduction of rivaroxaban, and the primary reason for dose reduction in the case of dabigatran (also, strong P-glycoprotein inhibitors), apixaban dose reduction requires 2 of 3 criteria (2). Importantly, apixaban can safely be administered in the standard dose to patients who meet only 1 of the dose-reduction criteria (age older than 80 years, weight <60 kg, serum creatinine >1.5 mg/dl) (3).
As for dabigatran, it is important to realize that dose reduction to 75 mg twice daily represents a regimen that has never been tested in a randomized clinical trial. Food and Drug Administration approval is based on pharmacokinetic and pharmacodynamic data (4). The same holds true for the current dosing recommendations with regard to the 4 available NOACs in cases of a creatinine clearance of <25 ml/min. In this context, results of randomized studies like RENAL-AF (Trial to Evaluate Anticoagulation Therapy in Hemodialysis Patients With Atrial Fibrillation) are eagerly awaited (5).
Appreciating that in the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) study, efficacy of dabigatran 110 mg twice daily was noninferior to VKA, with lower bleeding rates in >6,000 patients, it remains uncertain what the efficacy outcomes on dabigatran 75 mg twice daily are. For U.S. patients who meet a criterion for dose reduction with dabigatran (2), we advocate prescribing a properly dosed agent based on clinical evidence rather than choosing dabigatran 75 mg twice daily.
Please note: Dr. Verheugt has received consulting fees and honorariums from AstraZeneca, Bristol-Myers Squibb/Pfizer, Bayer, Daiichi-Sankyo, and Boehringer Ingelheim. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- 2017 American College of Cardiology Foundation
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