What do we need to be doing to use these drugs most effectively in clinical practice? 

First, remembering that these are blood thinners, patient selection is important, especially concerning adherence with these NOACs, because their biologic half-life is so short.  In addition, creatinine clearance is very important.  None of these agents was tested with a glomerular filtration rate <30 mL/min (although the cutoff in the ARISTOTLE, AMPLIFY and AMPLIFY-EXT trials with apixaban was 25 mL/min[19,20]), but the patient with end-stage renal disease is really not a candidate for the NOACs.

Second, we have to work out the best way to follow these patients.  For example, how often should they be monitored?  These patients are no longer tethered to their INR finger stick machine, but should they be followed up more closely just to ensure adherence?  What about assessing stability of renal function?  Blood pressure control and concomitant antiplatelet use?

All of us who prescribe these drugs need to be familiar with package inserts, because they are changing as new data emerge, especially around avoiding potent drug interactions and guidance on transitions from one class or drug to another.  Finally, for example, rivaroxaban  needs to be taken with a meal.