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Anticoagulation Endpoints With Clinical Implementation of Warfarin Pharmacogenetic Dosing in a Real‐World Setting: A Proposal for a New Pharmacogenetic Dosing Approach
Author(s) -
Arwood MJ,
Deng J,
Drozda K,
Pugach O,
Nutescu EA,
Schmidt S,
Duarte JD,
Cavallari LH
Publication year - 2017
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt.558
Subject(s) - dosing , pharmacogenetics , warfarin , medicine , intensive care medicine , pharmacology , biology , genotype , gene , atrial fibrillation , biochemistry
Achieving therapeutic anticoagulation efficiently with warfarin is important to reduce thrombotic and bleeding risks and is influenced by genotype. Utilizing data from a diverse population of 257 patients who received VKORC1 and CYP2C9 genotype‐guided warfarin dosing, we aimed to examine genotype‐associated differences in anticoagulation endpoints and derive a novel pharmacogenetic nomogram to more optimally dose warfarin. We observed significant differences across patients with 0, 1, or ≥2 reduced‐function VKORC1 or CYP2C9 alleles, respectively, in time to achieve therapeutic international normalized ratio (INR) (7.8 ± 5.8, 7.2 ± 4.7, and 5.4 ± 4.6 days, P = 0.0004) and mean percentage of time in therapeutic range in the first 28 days (22.2, 27.8, and 32.2%, P = 0.0127) with use of existing pharmacogenetic algorithms. These data suggest that more aggressive dosing is necessary for patients with 0 to 1 VKORC1/CYP2C9 variants to more efficiently achieve therapeutic anticoagulation. Herein, we provide a novel kinetic/pharmacodynamic‐derived dosing nomogram optimized for a heterogeneous patient population.