Assessment of Advantages and
Disadvantages of Agents Used For
Therapeutic Anticoagulation
Peter B. Berger, MD
Warfarin is an awful drug. That is not to say that it is not also a lifesaving
drug—it is. So many randomized controlled trials have demonstrated
warfarin’s remarkable ability to reduce embolic stroke in patients with
atrial fibrillation, the indication for warfarin that this article focuses on,
that it would be unethical to perform another placebo-controlled warfarin
trial in patients with atrial fibrillation who are able to tolerate the drug
(Table 1).
1-6
However, its numerous and profound limitations include a
narrow therapeutic range, requiring patients to have at least monthly
monitoring, a highly variable bioavailability between individuals, an
enormous number of both drug– drug and diet– drug interactions, and the
existence of common genetic polymorphisms that influence drug effect,
leading many to wonder whether the Food and Drug Administration
(FDA) would approve warfarin if it came to review in the current climate.
Currently there are more than a dozen anticoagulant drugs under
development in an attempt to replace warfarin for the prevention of stroke
and systemic embolism in patients with atrial fibrillation; two of them,
dabigatran and rivaroxaban, have been approved. Some of these antico-
agulants, like dabigatran, are thrombin (Factor II) inhibitors; others, like
rivaroxaban, apixaban, and edoxaban, are factor Xa inhibitors. Although
there are important differences between the pharmacologic characteristics
of these different drugs,
7-9
their most important characteristics—their
ability to reduce strokes and systemic emboli, and the frequency with
which they cause bleeding— can only be determined by large-scale
clinical trials. Accordingly, all 4 of those mentioned have been or are
undergoing evaluation in such trials, termed pivotal trials, because their
results determine whether the drugs are approved by the FDA.
9-12
Competing Interests: In the preceding 12 months, Dr. Berger has served as a consultant to
Boehringer Ingelheim, Novartis/Portola, and AstraZeneca. He has research funding from Thrombo-
vision, Helena, Accumetrics, AstraZeneca, Haemoscope, the Medicines Company, Corgenix/
Aspirinworks, Eli Lilly/Daiichi-Sankyo, Novartis, and Sanofi Aventis.
Dis Mon 2012;58:462-468
0011-5029/2012 $36.00 ϩ 0
http://dx.doi.org/10.1016/j.disamonth.2012.04.007
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