Maureen Price

A test of financial incentives to improve warfarin adherence

BackgroundSub-optimal adherence to warfarin places millions of patients at risk for stroke and bleeding complications each year. Novel methods are needed to improve adherence for warfarin. We conducted two pilot studies to determine whether a lottery-based daily financial incentive is feasible and improves warfarin adherence and anticoagulation control.MethodsVolunteers from the University of Pennsylvania Anticoagulation Management Center who had taken warfarin for at least 3 months participated in either a pilot study with a lottery with a daily expected value of

Dosing algorithms to predict warfarin maintenance dose in Caucasians and African Americans.

5 (N = 10) or a daily expected value of

Warfarin Response and Vitamin K Epoxide Reductase Complex 1 in African Americans and Caucasians

3 (N = 10). All subjects received use of an Informedix Med-eMonitor™ System with a daily reminder feature. If subjects opened up their pill compartments appropriately, they were entered into a daily lottery with a 1 in 5 chance of winning

Risk factors for nonadherence to warfarin: results from the IN-RANGE study†‡

10 and a 1 in 100 chance of winning

Apolipoprotein E genotype and warfarin dosing among Caucasians and African Americans

100 (pilot 1) or a 1 in 10 chance of winning

Warfarin and cytochrome P450 2C9 genotype: possible ethnic variation in warfarin sensitivity

10 and a 1 in 100 chance of winning

Can We Predict Daily Adherence to Warfarin?: Results From the International Normalized Ratio Adherence and Genetics (IN-RANGE) Study

100 (pilot 2). The primary study outcome was proportion of incorrect warfarin doses. The secondary outcome was proportion of INR measurements not within therapeutic range. Within-subject pre-post comparisons were done of INR measurements with comparisons with either historic means or within-subject comparisons of incorrect warfarin doses.ResultsIn the first pilot, the percent of out-of-range INRs decreased from 35.0% to 12.2% during the intervention, before increasing to 42% post-intervention. The mean proportion of incorrect pills taken during the intervention was 2.3% incorrect pills, compared with a historic mean of 22% incorrect pill taking in this clinic population. Among the five subjects who also had MEMS cap adherence data from warfarin use in our prior study, mean incorrect pill taking decreased from 26% pre-pilot to 2.8% in the pilot. In the second pilot, the time out of INR range decreased from 65.0% to 40.4%, with the proportion of mean incorrect pill taking dropping to 1.6%.ConclusionA daily lottery-based financial incentive demonstrated the potential for significant improvements in missed doses of warfarin and time out of INR range. Further testing should be done of this approach to determine its effectiveness and potential application to both warfarin and other chronic medications.

Intermediate Filaments in Striated Muscle

The objective of this study was to determine whether warfarin dosing algorithms developed for Caucasians and African Americans on the basis of clinical, environmental, and genetic factors will perform better than an empirical starting dose of 5 mg/day. From April 2002 through December 2005, 259 subjects (Caucasians and African Americans) who started using warfarin were prospectively followed until they reached maintenance dose. The Caucasian algorithm included 11 variables (R2 = 0.43). This model (which predicted 51% of the doses to within 1 mg of the observed dose) performed better than 5 mg/day (which predicted 29% of the doses to within 5 ± 1 mg). The African‐American algorithm included 10 variables (R2 = 0.28). This model predicted 37% of the doses to within 1 mg of the observed dose, representing a small improvement compared with 5 mg/day (which predicted 34% of the doses to within 1 mg of 5 mg/day). These results were similar to the results we obtained from testing other published algorithms. The dosing algorithms explained <45% of the observed variability in Caucasians, and the algorithms performed only marginally better for African Americans when compared with giving 5 mg empirically.

The Influence of Patient Adherence on Anticoagulation Control With Warfarin: Results From the International Normalized Ratio Adherence and Genetics (IN-RANGE) Study

The objective of this study was to determine whether two vitamin K epoxide reductase complex 1 (VKORC1) polymorphisms contribute to the variability in warfarin response, particularly in African Americans. The effect of the VKORC1 1173C/T and −1639G/A polymorphisms was examined in a prospective cohort study of 338 warfarin users. Subjects carrying an 1173T allele had a lower warfarin maintenance dose compared with subjects with the CC genotype in African Americans (−12.10 mg/week±4.93; P=0.02) and Caucasians (−14.41 mg/week±3.28; P<0.001). Before reaching maintenance dose, only Caucasians with the T allele had significantly increased risk of international normalized ratio >3 (odds ratio=3.10; 95% confidence interval: 1.73–5.55) compared with Caucasians with the CC genotype. Polymorphisms in the VKORC1 gene are associated with warfarin maintenance dose requirements among both African Americans and Caucasians. However, these polymorphisms may not be as useful in predicting over‐anticoagulation among African Americans.

Adherence to Warfarin Assessed by Electronic Pill Caps, Clinician Assessment, and Patient Reports: Results from the IN-RANGE Study

Warfarin is widely used to prevent stroke and venous thromboembolism despite its narrow therapeutic window. Warfarin nonadherence is a substantial problem, but risk factors have not been well elucidated.