Mental Illness and Warfarin Use in Atrial Fibrillation

Atrial fibrillation patients with mental illness are less likely to receive warfarin anticoagulation; those who do receive warfarin have excess risk of over-anticoagulation.
Published Online: September 06, 2011
Graham A. Walker, MD; Paul A. Heidenreich, MD, MS; Ciaran S. Phibbs, PhD; Alan S. Go, MD; Victor Y. Chiu, BA; Susan K. Schmitt, PhD; Lakshmi Ananth, MS; and Susan M. Frayne, MD, MPH

Objectives: To determine whether atrial fibrillation (AF) patients with mental health conditions (MHCs) were less likely than AF patients without MHCs to be prescribed warfarin and, if receiving warfarin, to maintain an International Normalized Ratio (INR) within the therapeutic range.


Study Design: Detailed chart review of AF patients using a Veterans Health Administration (VHA) facility in 2003.


Methods: For a random sample of 296 AF patients, records identified clinician-diagnosed MHCs (independent variable) and AF-related care in 2003 (dependent variables), receipt of warfarin, INR values below/above key thresholds, and time spent within the therapeutic range (2.0-3.0) or highly out of range. Differences between the MHC and comparison groups were examined using X2 tests and logistic regression controlling for age and comorbidity.


Results: Among warfarin-eligible AF patients (n = 246), 48.5% of those with MHCs versus 28.9% of those without MHCs were not treated with warfarin (P = .004). Among those receiving warfarin and monitored in VHA, highly supratherapeutic INRs were more common in the MHC group; for example, 27.3% versus 1.6% had any INR >5.0 (P <.001). Differences persisted after adjusting for age and comorbidity.


Conclusions: MHC patients with AF were less likely than those without MHC to have adequate management of their AF care. Interventions directed at AF patients with MHC may help to optimize their outcomes.

(Am J Manag Care. 2011;17(9):617-624)

Mental illness decreased likelihood of warfarin receipt among patients without recorded contraindications, but clinicians did not list mental illness as a rationale for withholding warfarin.


  • Among warfarin-treated patients, those with mental illness were more likely to have some International Normalized Ratio (INR) values substantially above the therapeutic range, but some with mental illness consistently maintained therapeutic INRs.


  • Identifying subgroups with mental illness who can/cannot safely take warfarin would inform interventions and guidelines.
The Veterans Health Administration (VHA) National Mental Health Strategic Plan has recently called attention to optimizing treatment of coexisting medical conditions in patients with mental illness. Research is beginning to amass suggesting that patients with mental health conditions (MHCs), representing nearly one third of Americans,1 may receive less intensive care for a range of conditions from diabetes to coronary artery disease to chronic pain.2-7 However, the influence of mental illness on the management of atrial fibrillation (AF) is not yet well understood. This is important because AF is highly prevalent, especially among older adults, and is associated with increased stroke risk.8,9 An oral anticoagulant, warfarin, reduces AF-related stroke risk from approximately 5% per year to 1% to 2% per year,8,10 but also has downsides: it increases major bleeding risk, it typically involves a complex and rigorous dosing schedule, and it requires frequent blood monitoring of coagulation status (International Normalized Ratio [INR]). Given warfarin’s narrow therapeutic window, clinicians may have concerns about whether patients with MHC can safely take warfarin as prescribed and follow through with necessary monitoring tests.

Unfortunately, major AF practice guidelines do not currently address whether mental illness should influence anticoagulant therapy decision making.11-13 This is concerning, since there are potential adverse consequences of prescribing warfarin for a patient who cannot use it safely: excess major bleeding if overdosed or thromboembolic events if underdosed. Likewise, there are potential adverse consequences of not prescribing warfarin for a patient who could take it safely, such as unnecessarily increased stroke risk.

Therefore, a detailed medical chart review methodology was used at 1 VHA facility to determine:

• Whether VHA AF patients with MHCs were less likely than those without MHCs to receive warfarin, even in the absence of contraindications.

• Whether, among those treated with warfarin and monitored in VHA, those with MHCs were more likely than those without MHCs to have INRs falling outside the standard therapeutic range.


Subjects and Chart Abstraction Procedure

Patients were drawn from a national database of AF/atrial flutter cases developed for another ongoing study, where AF was identified by the presence of International Classification of Diseases, Ninth Revision (ICD-9) code 427.3x in fiscal year 2001-2002 VHA or Medicare outpatient or inpatient administrative data. Patients with AF/atrial flutter were included regardless of whether or not the arrhythmia was thought to be paroxysmal, and regardless of duration of the diagnosis (except for transient AF; see below). From the 2490 members of this database who received more than 50% of their VHA outpatient care in both 2002 and 2003 at a suburban, West Coast VHA facility, a random sample of 450 was selected for detailed chart review of electronic medical records. After refining the standardized abstraction protocol on 50 cases not included in the study, a trained senior medical student identified information on variables of interest and recorded them on a standardized abstraction form. Ongoing quality control occurred at weekly meetings of the research team to ensure consistency in coding.14 Administrative data supplemented chart data for some variables.

Excluded were 6 patients with inaccurate chart record identifiers, 33 patients who died prior to the end of 2003, 17 patients with transient AF (occurring only during an acute hospitalization, or within 30 days of cardiac surgery or cardiac catheterization), and 98 with no VHA chart evidence of AF based on data from available electrocardiograms, patient problem list, or outpatient provider diagnoses from progress notes. (Among this latter subgroup, 75 were identified as having AF by Medicare ICD-9 codes only; likely their AF was managed by a non-VHA provider, and thus the diagnosis did not appear in VHA files.) A total of 296 AF cases (full cohort) were thus included in the study. Of these, 51 patients had evidence of 1 or more potential contraindications to warfarin: history of nonadherence, hemorrhage, falls, dementia, advanced liver disease, or malignancy.15 Among the remaining 246 patients, all of whom were apparently eligible to receive warfarin (warfarin-eligible subcohort), 161 (65.4%) received warfarin within or outside of VHA. Among them, 84 received their INR monitoring in the VHA Anticoagulation Clinic and had reliable INR data available, such that warfarin effect could be assessed; they constituted the warfarin-treated-VHA-monitored subcohort. This study was approved by the Institutional Review Board at Stanford University, Stanford, California.


The primary independent variable was MHC. MHC was defined as (1) 1 or more provider diagnosis of substance use disorder, depressive disorder, anxiety disorder, psychotic disorder, dysfunctional personality disorder, or bipolar disorder (in progress notes or problem lists) during 2001-2003; or (2) receipt of psychopharmacologic agents including antidepressants, antipsychotics, or mood stabilizers (based on the VHA medication log or based on a progress note referring to a non-VHA prescription) during 2001-2003.

Dependent variables included (1) receipt of warfarin in 2003 (yes/no), based upon the chart medication log or a progress note referring to a warfarin prescription by a non-VHA provider; (2) presence of at least 1 subtherapeutic INR in 2003 (<1.5, <2.0) based on laboratory result file data; and (3) presence of at least 1 supratherapeutic INR in 2003 (>3.0, >3.5, >4.0, >4.5, >5.0). A standard procedure was used to calculate time in therapeutic range (ie, the percentage of days in 2003 during which the INR fell within the 2.0 to 3.0 range, linearly interpolating INR values for days on which an actual value was not available).16 Time highly out of therapeutic range was calculated as percentage of days in 2003 during which the INR was less than 1.5 or greater than 4.0.

Other variables included known stroke risk factors for AF patients17: age 75 years or older, congestive heart failure, hypertension, diabetes, and prior nonhemorrhagic stroke or transient ischemic attack, based on 2001-2002 VHA outpatient or inpatient administrative data. Comorbidity was identified from the medical component of the Comorbidity Index (a count of medical conditions common in veterans and used for ambulatory care case-mix adjustment), using VHA administrative data.18,19 A count of primary care visits in 2003 came from clinic type codes in VHA administrative files. Patients were considered to have received only VHA care if they lacked any forms of outside insurance, based on the medical record, and if there was no mention of receipt of outside medical care or medications, based on primary care and cardiology clinic progress notes.

Analytic Approach

Among the full cohort, the warfarin-eligible subcohort, and the warfarin-treated-VHA-monitored subcohort, the following characteristics were examined for patients with and without MHC: demographics, stroke risk factors, Comorbidity Index, and utilization.

Among warfarin-eligible patients, the next analyses compared the proportions of those with and without MHC who were receiving warfarin, using a X2 test. In this group, multivariable logistic regression was performed to examine receipt of warfarin as a function of the presence of MHC, first unadjusted, then controlling for age, and then controlling for age and Comorbidity Index.

Next, among warfarin-treated-VHA-monitored patients, proportions were sequentially compared for those with and without MHC who had at least 1 low INR (<2.0, <1.5) and for those with and without MHC who had at least 1 high INR (>3.0, >3.5, >4.0, >4.5, >5.0), using a X2 test. Fisher’s exact test was used to calculate P values in instances of small cell size. Then logistic regression was used to examine high or low INR as a function of MHC, first unadjusted, then controlling for age, and then controlling for age and Comorbidity Index.

Among warfarin-treated-VHA-monitored patients, patients with and without MHC were compared with respect to mean time in therapeutic range and to mean time highly out of therapeutic range, using t tests.

Sensitivity analyses tested the stability of findings. Because of a concern that some VHA patients may receive their AF care from non-VHA providers, sensitivity analysis 1 examined the effect of restricting analyses to patients who used VHA as their exclusive source of care (ie, for whom all AF care could be reliably captured). Because of the possibility that some patients with a single recording of an AF diagnosis could have been miscoded as being an AF case, or could have had transient AF (despite efforts to exclude transient AF cases), sensitivity analysis 2 examined the effect of restricting analyses to patients who had at least 2 instances of an AF diagnosis from electrocardiograms or primary care/cardiology clinic notes.


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