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The American Journal of Managed Care November 2015
Community Pharmacy Automatic Refill Program Improves Adherence to Maintenance Therapy and Reduces Wasted Medication
Olga S. Matlin, PhD; Steven M. Kymes, PhD; Alice Averbukh, MBA, MS; Niteesh K. Choudhry, MD, PhD; Troyen A. Brennan, MD, MPH; Andrew Bunton, MBA, CFA; Timothy A. Ducharme, MBA; Peter D. Simmons, RPh;
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Elizabeth Levy Merrick, PhD, MSW; Dominic Hodgkin, PhD; Constance M. Horgan, ScD; Laura S. Lorenz, PhD; Lee Panas, MS; Grant A. Ritter, PhD; Paul Kasuba, MD; Debra Poskanzer, MD; and Renee Altman Nef
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Lena M. Chen, MD, MS; Ellen Meara, PhD; and John D. Birkmeyer, MD
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Sapna Kaul, PhD, MA; Anne C. Kirchhoff, PhD, MPH; Nancy E. Morden, MD, MPH; Christine S. Vogeli, PhD; and Eric G. Campbell, PhD
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Anticoagulation in Atrial Fibrillation: Impact of Mental Illness
Susan K. Schmitt, PhD; Mintu P. Turakhia, MD, MAS; Ciaran S. Phibbs, PhD; Rudolf H. Moos, PhD; Dan Berlowitz, MD, MPH; Paul Heidenreich, MD, MS; Victor Y. Chiu, MD; Alan S. Go, MD; Sarah A. Friedman
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Anticoagulation in Atrial Fibrillation: Impact of Mental Illness

Susan K. Schmitt, PhD; Mintu P. Turakhia, MD, MAS; Ciaran S. Phibbs, PhD; Rudolf H. Moos, PhD; Dan Berlowitz, MD, MPH; Paul Heidenreich, MD, MS; Victor Y. Chiu, MD; Alan S. Go, MD; Sarah A. Friedman
Atrial fibrillation patients with mental health conditions are less likely to be eligible for warfarin receipt, and those who are eligible receive warfarin at lower rates.


Objectives: To characterize warfarin eligibility and receipt among Veterans Health Administration (VHA) patients with and without mental health conditions (MHCs).

Study Design: Retrospective cohort study.

Methods: This observational study identified VHA atrial fibrillation (AF) patients with and without MHCs in 2004. We examined unadjusted MHC-related differences in warfarin eligibility and warfarin receipt among warfarin-eligible patients, using logistic regression for any MHC and for specific MHCs (adjusting for sociodemographic and clinical characteristics).

Results: Of 125,670 patients with AF, most (96.8%) were warfarin-eligible based on a CHADS2 stroke risk score. High stroke risk and contraindications to anticoagulation were both more common in patients with MHC. Warfarin-eligible patients with MHC were less likely to receive warfarin than those without MHC (adjusted odds ratio [AOR], 0.90; 95% CI, 0.87-0.94). The association between MHC and warfarin receipt among warfarin-eligible patients varied by specific MHC. Patients with anxiety disorders (AOR, 0.86; 95% CI, 0.80-0.93), psychotic disorders (AOR, 0.77; 95% CI, 0.65-0.90), and alcohol use disorders (AOR 0.62, 95% CI 0.54-0.72) were less likely to receive warfarin than patients without these conditions, whereas patients with depressive disorders and posttraumatic stress disorder were no less likely to receive warfarin than patients without these conditions.

Conclusions: Compared with patients with AF without MHCs, those with MHCs are less likely to be eligible for warfarin receipt and, among those eligible, are less likely to receive such treatment. Although patients with AF with MHC need careful assessment of bleeding risk, this finding suggests potential missed opportunities for more intensive therapy among some individuals with MHCs.

Am J Manag Care. 2015;21(11):e609-e617

Take-Away Points
  • Patients with atrial fibrillation and mental health conditions (MHCs) may not receive anticoagulation treatment, even when they exhibit indications for anticoagulation for stroke prevention. 
  • Atrial fibrillation patients with MHCs are a clinically complex group; stroke prevention decision making with this group of patients must be particularly deliberative. 
  • Clinicians should consider MHCs when developing an anticoagulation treatment plan, though presence of MHCs should not be considered an absolute contraindication to anticoagulation.
Atrial fibrillation and atrial flutter (AF, collectively) affect almost 7 million Americans1— including 6% of people aged over 65 years old2—and account for at least 15% of the 700,000 strokes per year in the United States.3 Anticoagulation with warfarin can decrease ischemic stroke risk in AF by more than 60%.4 However, warfarin has a narrow therapeutic window: subtherapeutic and supratherapeutic anticoagulation can cause ischemic and hemorrhagic stroke, respectively, making ongoing laboratory monitoring and dose titration necessary. Consequently, certain clinical scenarios preclude safe warfarin use, such as situations in which the risk of hemorrhage is high or the likelihood is low that the patient will be able to achieve and maintain good anticoagulation control.5-7 Healthcare providers may include patients with mental health conditions (MHCs) in the latter group due to concerns (founded or not) about effectiveness or safety of anticoagulation (eg, related to comorbidities, concomitant medications, or anticipated nonadherence). The Veterans Health Administration (VHA) has invested considerable resources in maintaining a robust anticoagulation care infrastructure, but does not provide explicit guidance on anticoagulation in the context of mental illness,7 despite the high prevalence of MHCs among VHA patients.8 Other national guidelines have provided scant input on this issue,5,6 and little research characterizes warfarin receipt among AF patients with MHCs.9-11 

We therefore performed a descriptive study of national data to determine: 1) whether AF patients with versus without MHCs differ in eligibility for anticoagulation; and 2) whether, among AF patients eligible for warfarin, warfarin receipt differs for patients with versus without MHC. The study was approved by the Institutional Review Board at Stanford University, Stanford, California.


We created a database containing variables characterizing AF care for all VHA patients with prevalent AF, as of the first day of fiscal year 2004. This database was created through a series of processing steps, quality checks, merges, and variable creation from VHA’s centralized inpatient and outpatient treatment and pharmacy databases, linked to Medicare inpatient and outpatient treatment claims data. Medicare pharmacy records were not available.


Figure 1 describes cohort construction. We used Veterans Affairs (VA) encounter data to identify all veterans using VHA outpatient care during 2004 who had AF as of the first day of 2004. AF was defined as the presence of at least 1 International Classification of Diseases, Ninth Revision (ICD-9-CM) AF diagnosis code 427.31 or 427.32 in 2002, and at least 1 confirmatory AF diagnosis in 2003 in VHA or Medicare inpatient or outpatient encounter records (based on records involving a face-to-face visit with a clinician). We excluded patients institutionalized for the majority of 2004, and those who received some of their 2004 VHA care outside of the continental United States (who thus might have incomplete data capture for processes of care). We also excluded patients whose MHC status could not be determined (see description of MHC variable creation below) to create “cohort 1.”

To examine warfarin receipt among patients with and without MHCs, we created “cohort 2,” which was the subset of cohort 1 patients who were apparently eligible for warfarin based on the presence of diagnosed stroke risk factors and absence of diagnosed contraindications to anticoagulation. 

Mental Health Conditions (independent variables)

Starting with the Agency for Health Research and Quality’s Clinical Classifications Software (CCS),12 we conducted an expert panel process to make modifications to the ICD-9-CM codes selected, and then mapped ICD-9-CM codes uniquely to 5 common specific MHCs (depressive disorders, posttraumatic stress disorder [PTSD], other anxiety disorders, psychotic disorders, and alcohol use disorders) and “other” psychiatric disorders. A patient was considered to be “MHC Yes” if he/she had at least 1 instance of an ICD-9-CM code falling into an MHC condition category during 2002-2003, plus at least 1 confirmatory ICD-9-CM code in 2004 (ie, during the period in which warfarin receipt was assessed), in a VHA or Medicare record associated with an outpatient face-to-face visit with a clinician or an inpatient record. A patient was considered to be “MHC No” if he/she had no instance of an MHC ICD-9-CM code in the entire interval of 2002 to 2004. Patients for whom MHC status was uncertain (ie, those with an MHC diagnosis at baseline [2002-2003] or during the study period [2004], but not both) were excluded, allowing for direct comparisons between the 2 distinct groups of “MHC Yes” and “MHC No.”

Separate dichotomous indicator variables were created for each of the 5 specific MHCs and for “other” MHCs for each patient. A patient could have more than 1 diagnosed MHC.

Eligibility for Anticoagulation (independent variable)

We examined patient characteristics suggesting greater eligibility for anticoagulation (ie, risk factors for stroke), and those suggesting less eligibility for anticoagulation (ie, risk factors for hemorrhage). To characterize stroke risk as of the start of the study period (ie, prior to 2004), we calculated the CHADS2 score, which gives 2 point each for being 75 years or older, having congestive heart failure, hypertension, or diabetes; and 2 points for prior stroke or transient ischemic attack.13 Based on available national guidelines during the study period, CHADS2 was recommended for stroke risk stratification, and warfarin was recommended for patients with AF who had a CHADS2 score of 2 or higher. Warfarin was recommended, but not required, in patients with a CHADS2 score of 1.5 Contraindications to anticoagulation included a history of intracranial hemorrhage, history of other hemorrhage, dementia, cirrhosis, seizure disorder, and end-stage renal disease.14 These conditions, and conditions included in the CHADS2 score, were identified based on ICD-9-CM codes in 2001 to 2003 VA and Medicare encounter data.

Warfarin Receipt (dependent variable)

VHA Decision Support System (DSS) pharmacy records contain a record of dispensed medications from all pharmacy orders entered by VHA clinicians. From the DSS data, we identified every outpatient warfarin prescription issued in the VHA in 2004 to patients in our warfarin-eligible analytic cohort (cohort 2). A patient was considered to have received warfarin if he/she received at least 2 VHA outpatient warfarin prescriptions in 2004, with at least 30 days between the start of one prescription and the start of another prescription. Although our focus was on warfarin receipt—rather than warfarin persistency or adherence, which would be better examined in a cohort of new warfarin users—we required 2 warfarin prescriptions to confirm that the patient was actively prescribed warfarin through the VHA, and that, for example, he/she had not merely been issued a single warfarin prescription as part of an emergency department visit. Prescriptions issued on the last day of an inpatient stay were counted as outpatient prescriptions because they represent discharge medications. Warfarin prescriptions issued by Medicare providers were not available to us.

Other Variables

Patient age, gender, race/ethnicity, and physical comorbidity index were derived from VHA and Medicare patient treatment databases. The Selim physical comorbidity index is a count of common nonpsychiatric medical conditions developed for VHA outpatient case-mix adjustment.15

Analytic Approach

In cohort 1 (AF patients, n = 125,670) and then in cohort 2 (AF patients eligible for warfarin, n = 87,248), we first compared those with versus without an MHC on sociodemographic characteristics, health status, and eligibility for anticoagulation (stroke and hemorrhage risk factors), using χ2 for categorical and t tests for continuous variables. Next, in cohort 2 we descriptively examined the proportion of patients who received warfarin, first by MHC status, and then in the subgroups with the 5 most common MHCs or with “other” MHCs. Finally, we performed 4 logistic regression analyses on cohort 2 to calculate unadjusted and adjusted odds of warfarin receipt (overall and by CHADS2 score) for patients with versus without diagnosed MHCs (Model 1 unadjusted and adjusted), and for patients with versus without specific MHCs (Model 2 unadjusted and adjusted). Because a patient could have more than 1 specific MHC (for example, a patient might have a depressive disorder, PTSD, and alcohol use disorder), Model 2 included a binary indicator variable for each of the 5 most common MHCs, and a binary indicator variable for other MHCs in aggregate, in a single logistic regression model; each estimate represents the conditional effect of each specific MHC, controlling for the presence of the other specific MHCs. Multivariate logistic regression models controlled for age as a continuous variable, gender, and physical comorbidities; overall models additionally controlled for stroke risk (CHADS2). 

After applying cohort selection and exclusion criteria, we identified 125,670 AF patients (cohort 1), and among them, 87,248 (69%) were apparently eligible for warfarin (cohort 2). Among cohort 1 patients, 22,247 (18%) had an MHC. Compared with patients without an MHC, patients with an MHC were younger (18% versus 8%, respectively, were under age 65) and slightly less likely to be male or Caucasian (Table 1). Among cohort 2 patients, 12,190 (14%) had any MHC—the most common specific MHCs were depressive disorders (7% of cohort 2 patients), PTSD (2%), other anxiety disorders (3%), psychotic disorders (1%), and alcohol use disorders (1%).

Eligibility for Anticoagulation Among All AF Patients

In cohort 1, indications for anticoagulation based on CHADS2 stroke risk index were greater in patients with an MHC. Nearly all AF patients (97% in both MHC and no MHC groups) were warfarin-eligible, based on a CHADS2 score of 1 or more (Table 1). A slightly greater proportion of patients with MHC than without MHC had high levels of stroke risk (ie, CHADS2 score ≥2). Regarding specific stroke risk factors in patients with versus without an MHC: respectively, 54% versus 48% had congestive heart failure; 91% versus 90% had hypertension; 41% versus 40% had diabetes; 39% versus 31%, had prior stroke or transient ischemic attack (Table 1).

Copyright AJMC 2006-2017 Clinical Care Targeted Communications Group, LLC. All Rights Reserved.
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