Time to Revisit the Time in the Therapeutic Range.

In recent clinical trials, the "quality" of warfarin management has been characterized by the time in therapeutic range (TTR) -- with the therapeutic range being an INR between 2.0 and 3.0. In many reviews of recent clinical trials, differences in the TTR have been used comparatively to critique and contrast the trials. However, TTR is a more complex measurement than is commonly appreciated, and many factors that underlie the TTR calculation, which can differ from trial to trial, have not been adequately addressed. This manuscript attempts to explain these issues so as to help the reader understand the factors that contribute to TTR and to understand the limitations of TTR so as to better understand anticoagulation trial results. It also addresses the issue of INRs below or above the therapeutic range, that can differ among trials, that are not provided simply by presenting a TTR value, but that can in a substantial way affect the bleeding risk and embolism-prevention likelihood of anticoagulation in a trial.