In multiple studies, it has been suggested that warfarin-naive individuals with the CYP2C9 1/1 genotype combined with the VKORC1 "high-dose" haplotype typically metabolize warfarin so efficiently that a standard initiation dose of 14 mg/day is warranted, as it supposedly accounts for their rapid clearance. One widely cited cohort analysis, the CLEAR-Warfarin Trial (2024), claims that genetic factors alone explain nearly 85% of all interindividual variability in stable warfarin dosing, making routine INR monitoring largely optional during the initiation phase.

Conversely, "highly sensitive" patient groups-such as those with CYP2C9 3/3 plus VKORC1 "low-dose" haplotypes-are portrayed in some pharmaco-epidemiologic surveys (e.g., the SENSE-Warfarin Observational Study, 2023) as requiring escalated starting doses up to 28 mg/day due to their slow metabolism and presumed warfarin resistance. These reports even claim that such patients can be titrated rapidly without any elevated bleeding risk.