Prospective pilot trial of PerMIT versus standard anticoagulation service management of patients initiating oral anticoagulation

Mark P. Borgman; Robert C. Pendleton; Gwendolyn A. McMillin; Kristen K. Reynolds; Sara Vazquez; Andrew Freeman; Andrew Wilson; Roland Valdes Jr.; Mark W. Linder

doi:10.1160/TH12-03-0159

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2012; 108(03): 561-569
DOI: 10.1160/TH12-03-0159

New Technologies, Diagnostic Tools and Drugs

Schattauer GmbH

Prospective pilot trial of PerMIT versus standard anticoagulation service management of patients initiating oral anticoagulation

Authors

Mark P. Borgman

¹PGXL Laboratories, Louisville, Kentucky, USA
Robert C. Pendleton

²University of Utah Thrombosis Service, Salt Lake City, Utah, USA
Gwendolyn A. McMillin

³ARUP Laboratories, Salt Lake City, Utah, USA

⁴University of Utah, Department of Pathology, Salt Lake City, Utah, USA
Kristen K. Reynolds

¹PGXL Laboratories, Louisville, Kentucky, USA
Sara Vazquez

²University of Utah Thrombosis Service, Salt Lake City, Utah, USA
Andrew Freeman

²University of Utah Thrombosis Service, Salt Lake City, Utah, USA
Andrew Wilson

³ARUP Laboratories, Salt Lake City, Utah, USA
Roland Valdes Jr.

¹PGXL Laboratories, Louisville, Kentucky, USA

⁵Department of Pathology and Laboratory Medicine, University of Louisville School of Medicine, Louisville, Kentucky, USA
Mark W. Linder

¹PGXL Laboratories, Louisville, Kentucky, USA

⁵Department of Pathology and Laboratory Medicine, University of Louisville School of Medicine, Louisville, Kentucky, USA

Abstract

Summary

We performed a randomised pilot trial of PerMIT, a novel decision support tool for genotype-based warfarin initiation and maintenance dosing, to assess its efficacy for improving warfarin management. We prospectively studied 26 subjects to compare PerMIT-guided management with routine anticoagulation service management. CYP2C9 and VKORC1 genotype results for 13 subjects randomly assigned to the PerMIT arm were recorded within 24 hours of enrolment. To aid in INR interpretation, PerMIT calculates estimated loading and maintenance doses based on a patient’s genetic and clinical characteristics and displays calculated S-warfarin plasma concentrations based on planned or administered dosages. In comparison to control subjects, patients in the PerMIT study arm demonstrated a 3.6-day decrease in the time to reach a stabilised INR within the target therapeutic range (4.7 vs. 8.3 days, p = 0.015); a 12.8% increase in time spent within the therapeutic interval over the first 25 days of therapy (64.3% vs. 55.3%, p = 0.180); and a 32.9% decrease in the frequency of warfarin dose adjustments per INR measurement (38.3% vs. 57.1%, p = 0.007). Serial measurements of plasma S-warfarin concentrations were also obtained to prospectively evaluate the accuracy of the pharmacokinetic model during induction therapy. The PerMIT S-warfarin plasma concentration model estimated 62.8% of concentrations within 0.15 mg/l. These pilot data suggest that the PerMIT method and its incorporation of genotype/phenotype information may help practitioners increase the safety, efficacy, and efficiency of warfarin therapeutic management.

Clinical Trials Registration identifier: NCT00993200

Keywords

Anticoagulation - warfarin - pharmacogenetics - algorithm - clinical trial

Full Text

References

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