A Randomized Trial Comparing Standard of Care to Bayesian Warfarin Dose Individualization

• Published in: Clinical pharmacology and therapeutics Vol. 115; no. 6; pp. 1316 - 1325
• Main Authors: Xue, Ling, Ma, Guangda, Holford, Nick, Qin, Qiong, Ding, Yinglong, Hannam, Jacqueline A., Ding, Xiaoliang, Fan, Hongyou, Ji, Zhenchun, Yang, Biwen, Shen, Han, Shen, Zhenya, Miao, Liyan
• Format: Journal Article
• Language: English
• Published: United States 01-06-2024
• Subjects: Aged; Anticoagulants - administration & dosage; Anticoagulants - adverse effects; Anticoagulants - pharmacokinetics; Bayes Theorem; Cardiac Surgical Procedures; Dose-Response Relationship, Drug; Drug Dosage Calculations; Drug Monitoring - methods; Female; Hemorrhage - chemically induced; Humans; International Normalized Ratio; Male; Middle Aged; Precision Medicine - methods; Prospective Studies; Single-Blind Method; Standard of Care; Warfarin - administration & dosage; Warfarin - adverse effects
• ISSN: 0009-9236; 1532-6535
• DOI: 10.1002/cpt.3207

The quality of warfarin treatment may be improved if management is guided by the use of models based upon pharmacokinetic‐pharmacodynamic theory. A prospective, two‐armed, single‐blind, randomized controlled trial compared management aided by a web‐based dose calculator (NextDose) with standard clinical care. Participants were 240 adults receiving warfarin therapy following cardiac surgery, followed up until the first outpatient appointment at least 3 months after warfarin initiation. We compared the percentage of time spent in the international normalized ratio acceptable range (%TIR) during the first 28 days following warfarin initiation, and %TIR and count of bleeding events over the entire follow‐up period. Two hundred thirty‐four participants were followed up to day 28 (NextDose: 116 and standard of care: 118), and 228 participants (114 per arm) were followed up to the final study visit. Median %TIR tended to be higher for participants receiving NextDose guided warfarin management during the first 28 days (63 vs. 56%, P = 0.13) and over the entire follow‐up period (74 vs. 71%, P = 0.04). The hazard of clinically relevant minor bleeding events was lower for participants in the NextDose arm (hazard ratio: 0.21, P = 0.041). In NextDose, there were 89.3% of proposed doses accepted by prescribers. NextDose guided dose management in cardiac surgery patients requiring warfarin was associated with an increase in %TIR across the full follow‐up period and fewer hemorrhagic events. A theory‐based, pharmacologically guided approach facilitates higher quality warfarin anticoagulation. An important practical benefit is a reduced requirement for clinical experience of warfarin management.