In Reply As was highlighted by Lozano and Franco, we recognize that there are numerous drug-drug interactions with warfarin, including selected medications that affect the activity of cytochrome P450, which may be administered to older adults with atrial fibrillation in conjunction with warfarin therapy. There are also significant dietary interactions with warfarin therapy that make maintenance of therapeutic levels challenging and underscore the need for ongoing vigilance while maintaining a therapeutic international normalized ratio. However, the main consequence of such interactions is an international normalized ratio frequently out of therapeutic range, and this value was captured in our “labile international normalized ratio” variable, which we found to be meaningfully associated with traumatic intracranial bleeding. We acknowledge that this variable represents the end point of multiple pathways, including intermittent drug-drug interactions, dietary changes, and poor adherence, and these elements need to be taken into consideration when discussing benefits and harm with warfarin therapy. Analysis of the specific elements leading to labile international normalized ratios within our sample is beyond the scope of our current investigation, although we believe this is a worthwhile direction for future studies.
John A. Dodson, J. Michael Gaziano. Effect of Drug Interactions and Adherence to Warfarin Therapy on Patients—Reply. JAMA Cardiol. 2016;1(7):850. doi:10.1001/jamacardio.2016.2313