In Reply Drs Li, Linnebur, Vazquez, Wang, Ms Sennesael, and their colleagues raise important issues concerning the mismatches between our estimates and the expected bleeding risk related to the potential change in NOAC concentration.1 The 12 drugs studied were chosen from a list of drugs potentially interacting with NOACs published by the European Heart Rhythm Association.2 Among them, phenytoin and rifampin were associated with more bleeding, although they decrease NOAC levels through CYP2A4 induction (which was incorrectly described as inhibition in the original article and has been corrected online). Conversely, digoxin and atorvastatin were associated with less bleeding even though they raise NOAC levels. These findings suggested that NOAC drug level is only one of many mechanisms contributing to complex drug-drug interactions among patients receiving NOACS.
Chang S, Wen M, Kuo C. Drug Interactions With Non–Vitamin K Oral Anticoagulants—Reply. JAMA. 2018;319(8):830–831. doi:10.1001/jama.2017.20854
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