Underprescribing vs underfilling to oral anticoagulation: An analysis of linked medical record and claims data for a nationwide sample of patients with atrial fibrillation.

BACKGROUND: Oral anticoagulants (OAC) is indicated for stroke prevention in patients with atrial fibrillation (AF) with a moderate or high risk of stroke. Despite the benefits of stroke prevention, only 50%-60% of Americans with nonvalvular AF and a moderate or high risk of stroke receive OAC medication. OBJECTIVE: To understand the extent to which low OAC use by patients with AF is attributed to underprescribing or underfilling once the medication is prescribed. METHODS: This is a retrospective cohort study that used linked claims data and electronic health records from Optum Integrated data. Participants were adults (aged ≥ 18 years) with first AF between January 2013 and June 2017. The outcomes included (1) being prescribed OACs within 180 days of AF diagnosis or not and (2) filling an OAC prescription or not among patients with AF who were prescribed an OAC within 150 days of AF diagnosis. Multivariable logistic regression models were constructed to determine factors associated with underprescribing and underfilling. RESULTS: Of the 6,141 individuals in the study cohort, 51% were not prescribed OACs within 6 months of their AF diagnosis. Of the 2,956 patients who were prescribed, 19% did not fill it at the pharmacy. In the final adjusted model, younger age, location (Northeast and South), a low CHA2DS2-VASc score, and a high HAS-BLED score were associated with a lower likelihood of being prescribed OACs. Among patients who were prescribed, Medicare enrollment (odds ratio [OR] [95% CI] = 2.2 [1.3-3.7]) and having a direct oral anticoagulant prescription (1.5 [1.2-1.9]) were associated with a lower likelihood of filling the prescription. CONCLUSIONS: Both underprescribing and underfilling are major drivers of low OAC use among patients with AF, and solutions to increase OAC use must address both prescribing and filling. DISCLOSURES: Research reported in this study was supported by the National Heart, Lung and Blood Institute (K01HL142847 and R01HL157051). Dr Guo is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (R01DK133465), PhMRA Foundation Research Starter Award, and the University of Florida Research Opportunity Seed Fund. Dr Hernandez reports scientific advisory board fees from Pfizer and Bristol Myers Squibb, outside of the submitted work.

Evaluation of COVID-19 Testing Strategies for Repopulating College and University Campuses: A Decision Tree Analysis.

PURPOSE: The optimal approach to identify SARS-CoV-2 infection among college students returning to campus is unknown. Recommendations vary from no testing to two tests per student. This research determined the strategy that optimizes the number of true positives and negatives detected and reverse transcription polymerase chain reaction (RT-PCR) tests needed. METHODS: A decision tree analysis evaluated five strategies: (1) classifying students with symptoms as having COVID-19, (2) RT-PCR testing for symptomatic students, (3) RT-PCR testing for all students, (4) RT-PCR testing for all students and retesting symptomatic students with a negative first test, and (5) RT-PCR testing for all students and retesting all students with a negative first test. The number of true positives, true negatives, RT-PCR tests, and RT-PCR tests per true positive (TTP) was calculated. RESULTS: Strategy 5 detected the most true positives but also required the most tests. The percentage of correctly identified infections was 40.6%, 29.0%, 53.7%, 72.5%, and 86.9% for Strategies 1-5, respectively. All RT-PCR strategies detected more true negatives than the symptom-only strategy. Analysis of TTP demonstrated that the repeat RT-PCR strategies weakly dominated the single RT-PCR strategy and that the thresholds for more intensive RT-PCR testing decreased as the prevalence of infection increased. CONCLUSION: Based on TTP, the single RT-PCR strategy is never preferred. If the cost of RT-PCR testing is of concern, a staged approach involving initial testing of all returning students followed by a repeat testing decision based on the measured prevalence of infection might be considered.

A behavioral economics-based telehealth intervention to improve aspirin adherence following hospitalization for acute coronary syndrome.

PURPOSE: A significant number of patients with acute coronary syndrome (ACS) are nonadherent to aspirin after hospital discharge, with an associated increased risk of subsequent cardiovascular events. The purpose of this pilot study was to test the efficacy of a telehealth intervention based on behavioral economics to improve aspirin adherence following hospitalization for ACS. METHODS: We enrolled 130 participants (c¯X = 58 ± 10.7 years of age, 38% female, 45% black) from two hospitals. Patients were eligible if they owned a smartphone and were admitted to the hospital for ACS, prescribed aspirin at discharge, and responsible for administering their own medications. Consenting participants were randomized to the intervention or usual care group. The intervention group was eligible to receive up to $50 per month if they took their medicine daily, with $2 per day deducted if a dose was missed. All participants received an electronic monitoring (EM) pill bottle containing a 90-day supply of aspirin, which was used to measure adherence calculated as the proportion of prescribed drug taken using the EM device. Based on the skewness in the adherence distribution, quantile regression was used to evaluate the effect of the intervention on median adherence over time. RESULTS: After 90 days, adherence fell in the control group but remained high in the intervention group (median adherence 81% vs 90%, P = .18). Rehospitalization was higher in the control group (24% vs 13%, P = .17). CONCLUSION: A loss aversion behavioral economics-based telehealth intervention is a promising approach to improving aspirin adherence following hospitalization for ACS.

The risk of sudden cardiac arrest and ventricular arrhythmia with rosiglitazone versus pioglitazone: real-world evidence on thiazolidinedione safety.

BACKGROUND: The low cost of thiazolidinediones makes them a potentially valuable therapeutic option for the > 300 million economically disadvantaged persons worldwide with type 2 diabetes mellitus. Differential selectivity of thiazolidinediones for peroxisome proliferator-activated receptors in the myocardium may lead to disparate arrhythmogenic effects. We examined real-world effects of thiazolidinediones on outpatient-originating sudden cardiac arrest (SCA) and ventricular arrhythmia (VA). METHODS: We conducted population-based high-dimensional propensity score-matched cohort studies in five Medicaid programs (California, Florida, New York, Ohio, Pennsylvania | 1999-2012) and a commercial health insurance plan (Optum Clinformatics | 2000-2016). We defined exposure based on incident rosiglitazone or pioglitazone dispensings; the latter served as an active comparator. We controlled for confounding by matching exposure groups on propensity score, informed by baseline covariates identified via a data adaptive approach. We ascertained SCA/VA outcomes precipitating hospital presentation using a validated, diagnosis-based algorithm. We generated marginal hazard ratios (HRs) via Cox proportional hazards regression that accounted for clustering within matched pairs. We prespecified Medicaid and Optum findings as primary and secondary, respectively; the latter served as a conceptual replication dataset. RESULTS: The adjusted HR for SCA/VA among rosiglitazone (vs. pioglitazone) users was 0.91 (0.75-1.10) in Medicaid and 0.88 (0.61-1.28) in Optum. Among Medicaid but not Optum enrollees, we found treatment effect heterogeneity by sex (adjusted HRs = 0.71 [0.54-0.93] and 1.16 [0.89-1.52] in men and women respectively, interaction term p-value = 0.01). CONCLUSIONS: Rosiglitazone and pioglitazone appear to be associated with similar risks of SCA/VA.

Predictive risk stratification using HEART (history, electrocardiogram, age, risk factors, and initial troponin) and TIMI (thrombolysis in myocardial infarction) scores in non-high risk chest pain patients: An African American urban community based hospital study.

Validated risk scoring systems in African American (AA) population are under studied. We utilized history, electrocardiogram, age, risk factors, and initial troponin (HEART) and thrombolysis in myocardial infarction (TIMI) scores to predict major adverse cardiovascular events (MACE) in non-high cardiovascular (CV) risk predominantly AA patient population.A retrospective emergency department (ED) charts review of 1266 chest pain patients where HEART and TIMI scores were calculated for each patient. Logistic regression model was computed to predict 6-week and 1-year MACE and 90-day cardiac readmission. Decision curve analysis (DCA) was constructed to differentiate between clinical strategies in non-high CV risk patients.Of the 817 patients included, 500 patients had low HEART score vs. 317 patients who had moderate HEART score. Six hundred sixty-three patients had low TIMI score vs. 154 patients had high TIMI score. The univariate logistic regression model shows odds ratio of predicting 6-week MACE using HEART score was 3.11 (95% confidence interval [CI] 1.43-6.76, P = .004) with increase in risk category from low to moderate vs. 2.07 (95% CI 1.18-3.63, P = .011) using TIMI score with increase in risk category from low to high and c-statistic of 0.86 vs. 0.79, respectively. DCA showed net benefit of using HEART score is equally predictive of 6-week MACE when compared to TIMI.In non-high CV risk AA patients, HEART score is better predictive tool for 6-week MACE when compared to TIMI score. Furthermore, patients presenting to ED with chest pain, the optimal strategy for a 2% to 4% miss rate threshold probability should be to discharge these patients from the ED.

Palliative Care in Heart Failure: Rationale, Evidence, and Future Priorities.

Patients with heart failure (HF) and their families experience stress and suffering from a variety of sources over the course of the HF experience. Palliative care is an interdisciplinary service and an overall approach to care that improves quality of life and alleviates suffering for those living with serious illness, regardless of prognosis. In this review, we synthesize the evidence from randomized clinical trials of palliative care interventions in HF. While the evidence base for palliative care in HF is promising, it is still in its infancy and requires additional high-quality, methodologically sound studies to clearly elucidate the role of palliative care for patients and families living with the burdens of HF. Yet, an increase in attention to primary palliative care (e.g., basic physical and emotional symptom management, advance care planning), provided by primary care and cardiology clinicians, may be a vehicle to address unmet palliative needs earlier and throughout the illness course.

Gastrointestinal bleeding and intracranial hemorrhage in concomitant users of warfarin and antihyperlipidemics.

BACKGROUND: Drug interactions, particularly those involving warfarin, are a major clinical and public health problem. Minimizing serious bleeding caused by anticoagulants is a recent major focus of the United States (US) Department of Health and Human Services. This study quantified the risk of gastrointestinal bleeding (GIB) and intracranial hemorrhage (ICH) among concomitant users of warfarin and individual antihyperlipidemics. METHODS: The authors conducted a high-dimensional propensity score-adjusted cohort study of new concomitant users of warfarin and an antihyperlipidemic, among US Medicaid beneficiaries from five states during 1999-2011. Exposure was defined by concomitant use of warfarin plus one of eight antihyperlipidemics. The primary outcome measure was a composite of GIB/ICH within the first 30days of concomitant use. As a secondary outcome measure, GIB/ICH was examined within the first 180days of concomitant use. RESULTS: Among 236,691 persons newly-exposed to warfarin and an antihyperlipidemic, the crude incidence of GIB/ICH was 13.2 (95% confidence interval 12.7 to 13.8) per 100person-years. Users were predominantly older, female, and Caucasian. Adjusted hazard ratios (aHRs) for warfarin and individual statins were consistent with no association. Warfarin+gemfibrozil was associated with an 80% increased risk of GIB/ICH within the first month of concomitant use (aHR=1.8, 1.4 to 2.4). Warfarin+fenofibrate was associated with a similar increased risk (aHR=1.8, 1.2 to 2.7), yet with an onset during the second month of concomitant use. CONCLUSIONS: Among warfarin-treated persons, the use of fibrates-but not statins-increases the risk of hospital presentation for GIB/ICH.

Predicting prolonged dose titration in patients starting warfarin.

PURPOSE: Patients initiating warfarin therapy generally experience a dose-titration period of weeks to months, during which time they are at higher risk of both thromboembolic and bleeding events. Accurate prediction of prolonged dose titration could help clinicians determine which patients might be better treated by alternative anticoagulants that, while more costly, do not require dose titration. METHODS: A prediction model was derived in a prospective cohort of patients starting warfarin (n = 390), using Cox regression, and validated in an external cohort (n = 663) from a later time period. Prolonged dose titration was defined as a dose-titration period >12 weeks. Predictor variables were selected using a modified best subsets algorithm, using leave-one-out cross-validation to reduce overfitting. RESULTS: The final model had five variables: warfarin indication, insurance status, number of doctor's visits in the previous year, smoking status, and heart failure. The area under the ROC curve (AUC) in the derivation cohort was 0.66 (95%CI 0.60, 0.74) using leave-one-out cross-validation, but only 0.59 (95%CI 0.54, 0.64) in the external validation cohort, and varied across clinics. Including genetic factors in the model did not improve the area under the ROC curve (0.59; 95%CI 0.54, 0.65). Relative utility curves indicated that the model was unlikely to provide a clinically meaningful benefit compared with no prediction. CONCLUSIONS: Our results suggest that prolonged dose titration cannot be accurately predicted in warfarin patients using traditional clinical, social, and genetic predictors, and that accurate prediction will need to accommodate heterogeneities across clinical sites and over time. Copyright © 2016 John Wiley & Sons, Ltd.

A randomized controlled trial of co-payment elimination: the CHORD trial.

OBJECTIVES: Efforts to improve adherence by reducing co-payments through value-based insurance design are become more prevalent despite limited evidence of improved health outcomes. The objective of this study was to determine whether eliminating patient co-payments for blood pressure medications improves blood pressure control. STUDY DESIGN: Randomized controlled trial. METHODS: The Collaboration to Reduce Disparities in Hypertension (CHORD) was a randomized controlled trial with 12 months' follow-up conducted among patients from the Philadelphia and Pittsburgh Veterans Administration Medical Centers. We enrolled 479 patients with poorly controlled systolic blood pressure. Participants were randomly assigned to: a) receive reductions in co-payments from $8 to $0 per medication per month for each antihypertensive prescription filled, b) a computerized behavioral intervention (CBI), c) both co-pay reduction and CBI, or d) usual care. Our main outcome measure was change in systolic blood pressure from enrollment to 12 months post enrollment. We also measured adherence using the medication possession ratio in a subset of participants. RESULTS: There were no significant interactions between the co-payment interventions and the CBI interventions. There was no relative difference in the change in medication possession ratio between baseline and 12 months (0.05% and -.90% in control and incentive groups, respectively; P = .74) or in continuous medication gaps of 30, 60, or 90 days. Blood pressure decreased among all participants, but to a similar degree between the financial incentive and control groups. Systolic pressure within the incentive group dropped 13.2 mm Hg versus 15.2 mm Hg for the control group (difference = 2.0; 95% CI, -2.3 to 6.3; P = .36). The proportion of patients with blood pressure under control at 12 months was 29.5% in the incentive group versus 33.9 in the control group (odds ratio, 0.8; 95% CI, 0.5-1.3; P = .36). CONCLUSIONS: Among patients with poorly controlled blood pressure, financial incentives--as implemented in this trial--that reduced patient cost sharing for blood pressure medications did not improve medication adherence or blood pressure control.

A randomized controlled trial of negative co-payments: the CHORD trial.

OBJECTIVES: Value-based insurance designs are being widely used. We undertook this study to examine whether a financial incentive that lowered co-payments for blood pressure medications below $0 improved blood pressure control among patients with poorly controlled hypertension. STUDY DESIGN: Randomized controlled trial. METHODS: Participants from 3 Pennsylvania hospitals (n = 337) were randomly assigned to: a) be paid $8 per medication per month for filling blood pressure prescriptions, b) a computerized behavioral intervention (CBI), c) both payment and CBI, or d) usual care. The primary outcome was change in blood pressure between baseline and 12 months post enrollment. We also measured adherence using the medication possession ratio in a subset of participants. RESULTS: There were no significant interactions between the incentive and the CBI interventions. There were no significant changes in medication possession ratio in the treatment group. Blood pressure decreased among all participants, but to a similar degree between the financial incentive and control groups. Systolic blood pressure (SBP) dropped 13.7 mm Hg for the incentive group versus 10.0 mm Hg for the control group (difference = ­3.7; 95% CI, ­9.0 to 1.6; P = .17). The proportion of patients with blood pressure under control 12 months post enrollment was 35.6% of the incentive group versus 27.7% of the control group (odds ratio, 1.4; 95% CI, 0.8-2.5; P = .19). Diabetics in the incentive group had an average drop in SBP of 12.7 mm Hg between baseline and 12 months compared with 4.0 mm Hg in the control group (P = .02). Patients in the incentive group without diabetes experienced average SBP reductions of 15.0 mm Hg, compared with 16.3 mm Hg for control group nondiabetics (P = .71). CONCLUSIONS: Among patients with poorly controlled blood pressure, financial incentives­as implemented in this trial­did not improve blood pressure control or adherence except among patients with diabetes.

Antipsychotics and the Risks of Sudden Cardiac Death and All-Cause Death: Cohort Studies in Medicaid and Dually-Eligible Medicaid-Medicare Beneficiaries of Five States.

CONTEXT: Antipsychotic drugs have been linked to QT-interval prolongation, a presumed marker of cardiac risk, and torsade de pointes. OBJECTIVE: To examine the associations between antipsychotics and 1) outpatient-originated sudden cardiac death and ventricular arrhythmia (SD/VA) and 2) all-cause death. DESIGN: Two retrospective cohort studies. SETTING: Medicaid programs of California, Florida, New York, Ohio and Pennsylvania. PATIENTS: Incident antipsychotic users aged 30-75 years. MAIN OUTCOME MEASURES: 1) Incident, first-listed emergency department or principal inpatient SD/VA diagnoses; and 2) death reported in the Social Security Administration Death Master File. RESULTS: Among 459,614 incident antipsychotic users, the incidences of SD/VA and death were 3.4 and 35.1 per 1,000 person-years, respectively. Compared to olanzapine as the referent, adjusted hazard ratios (HRs) for SD/VA were 2.06 (95% CI, 1.20-3.53) for chlorpromazine, 1.72 (1.28-2.31) for haloperidol, and 0.73 (0.57-0.93) for quetiapine. Adjusted HRs for perphenazine and risperidone were consistent with unity. In a subanalysis limited to first prescription exposures, HRs for chlorpromazine and haloperidol were further elevated (2.54 [1.07-5.99] and 2.68 [1.59-4.53], respectively), with the latter exhibiting a dose-response relationship. Results for death were similar. CONCLUSIONS: Haloperidol and chlorpromazine had less favorable cardiac safety profiles than olanzapine. Among atypical agents, risperidone had a similar cardiac safety profile to olanzapine, whereas quetiapine was associated with 30% and 20% lower risks of SD/VA and death, respectively, compared to olanzapine. These measured risks do not correlate well with average QT prolongation, further supporting the notion that average QT prolongation may be a poor surrogate of antipsychotic arrhythmogenicity.

Novel incentive-based approaches to adherence.

BACKGROUND: Adherence to medications for chronic conditions is often very low, limiting the benefit to patients, even when the medications are effective and have favorable side effect profiles. PURPOSE: This article reviews some of the prior work on treatment adherence, introduces novel concepts from behavioral economics that can be used to design interventions to improve adherence, and proposes new approaches for clinical trials. METHODS: Relevant experience of the authors and insights from the literature were combined to identify key issues and propose methodological improvements. Specific examples regarding adherence to warfarin are provided. RESULTS: Several new approaches to trial design can be effectively applied in the context of medication adherence. These include tailored intervention strategies and sequential multiple assignment randomized trial (SMART) designs. LIMITATIONS: While we have proposed to use these new approaches for ongoing studies of adherence in behavioral health, practical experience with their application is still somewhat limited. CONCLUSIONS: Behavioral economics offer a variety of concepts that, when used in the design of interventions to improve adherence, may be more successful than traditional approaches. New clinical trial designs can also be adopted to improve the efficiency of studies that assess these approaches.

Medication adherence: a call for action.

Poor adherence to efficacious cardiovascular-related medications has led to considerable morbidity, mortality, and avoidable health care costs. This article provides results of a recent think-tank meeting in which various stakeholder groups representing key experts from consumers, community health providers, the academic community, decision-making government officials (Food and Drug Administration, National Institutes of Health, etc), and industry scientists met to evaluate the current status of medication adherence and provide recommendations for improving outcomes. Below, we review the magnitude of the problem of medication adherence, prevalence, impact, and cost. We then summarize proven effective approaches and conclude with a discussion of recommendations to address this growing and significant public health issue of medication nonadherence.

Validation of diagnostic codes for outpatient-originating sudden cardiac death and ventricular arrhythmia in Medicaid and Medicare claims data.

PURPOSE: Sudden cardiac death (SD) and ventricular arrhythmias (VAs) caused by medications have arisen as an important public health concern in recent years. The validity of diagnostic codes in identifying SD/VA events originating in the ambulatory setting is not well known. This study examined the positive predictive value (PPV) of hospitalization and emergency department encounter diagnoses in identifying SD/VA events originating in the outpatient setting. METHODS: We selected random samples of hospitalizations and emergency department claims with principal or first-listed discharge diagnosis codes indicative of SD/VA in individuals contributing at least 6 months of baseline time within 1999-2002 Medicaid and Medicare data from five large states. We then obtained and reviewed medical records corresponding to these events to serve as the reference standard. RESULTS: We identified 5239 inpatient and 29 135 emergency department events, randomly selected 100 of each, and obtained 119 medical records, 116 of which were for the requested courses of care. The PPVs for an outpatient-originating SD/VA precipitating hospitalization or emergency department treatment were 85.3% (95% confidence interval [CI] = 77.6-91.2) overall, 79.7% (95%CI = 68.3-88.4) for hospitalization claims, and 93.6% (95%CI = 82.5-98.7) for emergency department claims. CONCLUSIONS: First-listed SD/VA diagnostic codes identified in inpatient or emergency department encounters had very good agreement with clinical diagnoses and functioned well to identify outpatient-originating events. Researchers using such codes can be confident of the PPV when conducting studies of SD/VA originating in the outpatient setting.

Impact of a prescription copayment increase on lipid-lowering medication adherence in veterans.

BACKGROUND: In February 2002, the Department of Veterans Affairs (VA) increased copayments from $2 to $7 per 30-day drug supply of each medication for many veterans. We examined the impact of the copayment increase on lipid-lowering medication adherence. METHODS AND RESULTS: This quasiexperimental study used electronic records of 5604 veterans receiving care at the Philadelphia VA Medical Center from November 1999 to April 2004. The all copayment group included veterans subject to copayments for all drugs with no annual cap. Veterans subject to copayments for drugs only if indicated for a non-service-connected condition with an annual cap of $840 for out-of-pocket costs made up the some copayment group. Veterans who remained copayment exempt formed a natural control group (no copayment group). Patients were identified as adherent if the proportion of days covered with lipid-lowering medications was > or =80%. Patients were identified as having a continuous gap if they had at least 1 continuous episode with no lipid-lowering medications for > or =90 days. A difference-in-difference approach compared changes in lipid-lowering medication adherence during the 24 months before and after copayment increase among veterans subject to the copayment change with those who were not. Adherence declined in all 3 groups after the copayment increase. However, the percentage of patients who were adherent (proportion of days covered > or =80%) declined significantly more in the all copayment (-19.2%) and some copayment (-19.3%) groups relative to the exempt group (-11.9%). The incidence of a continuous gap increased significantly at twice the rate in both copayment groups (all copayment group, 24.6%; some copayment group, 24.1%) as the exempt group (11.7%). Compared with the exempt group, the odds of having a continuous gap in the after relative to the before period were significantly higher in both the all copayment group (odds ratio, 3.04; 95% confidence interval, 2.29 to 4.03) and the some copayment group (odds ratio, 1.85; 95% confidence interval, 1.43 to 2.40). Similar results were seen in subgroups of patients at high risk for coronary heart disease, high medication users, and elderly veterans. CONCLUSIONS: The copayment increase adversely affected lipid-lowering medication adherence among veterans, including those at high coronary heart disease risk.

A test of financial incentives to improve warfarin adherence.

BACKGROUND: Sub-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. METHODS: Volunteers 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 $5 (N = 10) or a daily expected value of $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 $10 and a 1 in 100 chance of winning $100 (pilot 1) or a 1 in 10 chance of winning $10 and a 1 in 100 chance of winning $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. RESULTS: In 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%. CONCLUSION: A 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.

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

BACKGROUND: 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. METHODS: A prospective cohort study of adults initiating warfarin at two anticoagulation clinics (University and VA-affiliated) was performed to determine factors affecting nonadherence to warfarin. Nonadherence, defined by failure to record a correct pill bottle opening each day, was measured daily via electronic medication event monitoring systems (MEMS) caps. A multivariable explanatory model using logistic regression for longitudinal data was used to identify risk factors for nonadherence. RESULTS: One hundred eleven subjects were followed for a median of 137 days. Warfarin nonadherence was common (4787 of 22,425 or 21% of patient-days observed). Factors independently associated with higher odds of nonadherence included education beyond high school (odds ratio (OR) 1.8 (95%CI 1.2-2.7)), lower Short Form (SF)-36 mental component score (OR 1.4 (1.1-1.6) for each 10 point decrease); and impaired cognition (< or =19 points) on the Cognitive Capacity Screening Examination (CCSE) (OR 2.9 (1.7-4.8)). Compared to currently employed subjects, unemployed (OR 0.6 (0.3-1.2)) and retired (OR 0.5 (0.3-0.8)) subjects had somewhat improved adherence; disabled subjects over age 55 had worse adherence (OR 1.8 (1.1-3.1)) than younger disabled subjects (OR 0.8 (0.4-1.5)). CONCLUSIONS: Poor adherence to warfarin is common and risk factors are related to education level, employment status, mental health functioning, and cognitive impairment. Within the carefully controlled anticoagulation clinic setting, such patient-specific factors may be the basis of future interventions to improve nonadherence.

Adherence to warfarin assessed by electronic pill caps, clinician assessment, and patient reports: results from the IN-RANGE study.

BACKGROUND: Patient adherence to warfarin may influence anticoagulation control; yet, adherence among warfarin users has not been rigorously studied. OBJECTIVE: Our goal was to quantify warfarin adherence over time and to compare electronic medication event monitoring systems (MEMS) cap measurements with both self-report and clinician assessment of patient adherence. DESIGN: We performed a prospective cohort study of warfarin users at 3 Pennsylvania-based anticoagulation clinics and assessed pill-taking behaviors using MEMS caps, patient reports, and clinician assessments. RESULTS: Among 145 participants, the mean percent of days of nonadherence by MEMS was 21.8% (standard deviation+/-21.1%). Participants were about 6 times more likely to take too few pills than to take extra pills (18.8 vs. 3.3%). Adherence changed over time, initially worsening over the first 6 months of monitoring, which was followed by improvement beyond 6 months. Although clinicians were statistically better than chance at correctly labeling a participant's adherence (odds ratio = 2.05, p = 0.015), their estimates often did not correlate with MEMS-cap data; clinicians judged participants to be "adherent" at 82.8% of visits that were categorized as moderately nonadherent using MEMS-cap data (>or=20% nonadherence days). Similarly, at visits when participants were moderately nonadherent by MEMS, they self-reported perfect adherence 77.9% of the time. CONCLUSIONS: These results suggest that patients may benefit from adherence counseling even when they claim to be taking their warfarin or the clinician feels they are doing so, particularly several months into their course of therapy.