Laboratory and clinical outcomes of pharmacogenetic vs. clinical protocols for warfarin initiation in orthopedic patients.

BACKGROUND: Warfarin is commonly prescribed for prophylaxis and treatment of thromboembolism after orthopedic surgery. During warfarin initiation, out-of-range International Normalized Ratio (INR) values and adverse events are common. METHODS: In orthopedic patients beginning warfarin therapy, we developed and prospectively validated pharmacogenetic and clinical dose refinement algorithms to revise the estimated therapeutic dose after 4 days of therapy. RESULTS: The pharmacogenetic algorithm used the cytochrome P450 (CYP) 2C9 genotype, smoking status, peri-operative blood loss, liver disease, INR values and dose history to predict the therapeutic dose. The R(2) was 82% in a derivation cohort (n = 86) and 70% when used prospectively (n = 146). The R(2) of the clinical algorithm that used INR values and dose history to predict the therapeutic dose was 57% in a derivation cohort (n = 178) and 48% in a prospective validation cohort (n = 146). In 1 month of prospective follow-up, the percent time spent in the therapeutic range was 7% higher (95% CI: 2.7-11.7) in the pharmacogenetic cohort. The risk of a laboratory or clinical adverse event was also significantly reduced in the pharmacogenetic cohort (Hazard Ratio 0.54; 95% CI: 0.30-0.97). CONCLUSIONS: Warfarin dose adjustments that incorporate genotype and clinical variables available after four warfarin doses are accurate. In this non-randomized, prospective study, pharmacogenetic dose refinements were associated with more time spent in the therapeutic range and fewer laboratory or clinical adverse events. To facilitate gene-guided warfarin dosing we created a non-profit website, http://www.WarfarinDosing.org.

Establishing and running an effective telephone-based anticoagulation service.

Observational studies and randomized controlled trials have revealed improvement in international normalized ratio (INR) control and reduced thrombotic and hemorrhagic events in patients taking warfarin who are managed by an anticoagulation service (ACS) compared with traditional physician care. In this article, we describe how to establish a multidisciplinary telephone-based ACS to monitor INRs, dose warfarin, and heparin therapy, and to educate patients by telephone. We address how to improve ACS efficiency by using an electronic medical record, charting by exception, holding group-based education, communicating by telephone, and conducting quality assurance. We also make recommendations for improving the quality of care of patients taking anticoagulants that can be implemented in any setting and we discuss how to apply these guidelines to other remote disease-state management programs (eg, diabetes).