Common clinical variables predict warfarin maintenance dose and therapeutic resistance

Excerpt

Introduction Several warfarin dosing strategies have been proposed, primarily based on experience with induction therapy in small clinical cohorts. Due to these limitations, optimal empiric dosing remains unknown. One current strategy is to identify patients with decreased warfarin sensitivity (via single nucleotide polymorphism genotyping) at the onset of therapy to allow for early dose adjustment. However, it may be more efficient to identify common clinical variables that are predictive of maintenance dose requirements and will also identify patients who would benefit from genetic testing. Methods Retrospective analysis of dose and clinical variables from a large, real-time warfarin management database (CoagClinic^®). Eligible patients: both goal and therapeutic INR 2–3; treatment duration >1 month; >5 INR values; and age, gender, and body weight available. Patients were stratified by age (bi-deciles) and simple statistics applied to determine mean, standard deviation, and range of doses; further stratified by gender. Results 456,695 visits amongst 12,929 patients aged 69.2 ± 13.1 years (mean ± SD) from 106 institutions met criteria for inclusion. The cohort was 54.3% male with a mean of 35.4 visits/patient, the patients weighed 84.7 ± 22.5 kg. The treatment period recorded was 2.03 ± 1.4 years/patient. The mean therapeutic INR for the cohort was 2.45 ± 0.21. The mean weekly dose for the cohort was 29.7 ± 14.9 mg. As previously described by others, the maintenance dose was inversely proportional to age. Also, as previously described, dose was directly proportional to body weight. Correcting the dose for body weight revealed that males have a slightly lower dose requirement that becomes gender neutral with advanced age. This is in contrast to reports of continued gender inequality of dose in other reports and may be due to changes in lean body mass with advanced age. Conclusions This is the largest cohort of patients for which warfarin dose requirements have been described. These data confirm previous information regarding the relationships between dose, gender, and body weight, but reveal that the gender inequality of dose requirement disappears with advanced age when utilizing weight adjusted dosing. This may be due to changes in lean body mass with advanced age. Further, when dose is adjusted for weight, gender and age can be used to predict maintenance dose requirements. Also, this information can be utilized to objectively define “warfarin resistance,” as those requiring >2 standard deviations above the mean dose for that gender and bi-decile; thus identifying patients who may benefit from genetic testing. …