BACKGROUND/RATIONALE:
Atrial fibrillation is common, affecting 2.2 million Americans and is likely to increase with the aging of the US population. National guidelines recommend warfarin, an oral anticoagulant for patients with atrial fibrillation and multiple risk factors (e.g., hypertension, diabetes, older age, stroke or TIA, heart failure) to reduce the stroke risk. Veterans prescribed warfarin are usually managed closely in anti-coagulation clinics. Prior meta-analysis suggests that patients on warfarin managed in these clinics have better anticoagulation control compared to patients followed in non-specialized clinics.

Dabigatran is a newly approved oral direct thrombin inhibitor that was demonstrated to be more efficacious than warfarin for patients with atrial fibrillation. In the RE-LY trial, dabigatran reduced stroke and systemic embolism (Relative risk 0.66; 95% CI, 0.53 to 0.82; P<0.001) with a similar risk of major bleeding (3.36% vs. 3.11% per year; for warfarin vs. dabigatran p=0.31).

Non-adherence to cardiovascular medications is common, often declining over time, and limits the effectiveness of medications in routine clinical practice.

For anticoagulation therapy, pharmacists have helped patients maintain better INR control via anti-coagulation clinics compared to patients not managed in these clinics. An intervention focusing on adherence involving pharmacists can have the potential to improve dabigatran use so that the benefits demonstrated in the clinical trials for dabigatran can be realized in routine clinical practice.

OBJECTIVE(S):
Aims
1. Conduct key informant interviews with patient sample (n=30) recently started on dabigatran for atrial fibrillation to determine barriers/facilitators to dabigatran adherence.

2. Conduct key informant interviews with pharmacist sample (n=20) in anti-coagulation clinics to understand their perspectives on barriers/facilitators to patients' maintaining dabigatran adherence.

3. Informed by the qualitative interviews, develop and pilot test a multi-faceted intervention targeting patients/pharmacists to improve dabigatran adherence.


METHODS:
This mixed methods study employed qualitative methods to understand patient/provider identified barriers/facilitators to dabigatran adherence. Informed by interviews (aims 1 and 2), we refined the proposed dabigatran adherence intervention (aim 3) that incorporates elements from prior studies that have improved chronic cardiovascular medication adherence and include: patient education, tele-monitoring, and pharmacy service follow-up. Finally, we pilot tested this intervention to assess its effectiveness to improve timely refill of dabigatran (n=150) among patients recently started on dabigatran for atrial fibrillation at the Denver VAMC.
Patients who have transitioned from warfarin to dabigatran or were recently started on anti-coagulation were eligible. Patient who did not have a telephone or for whom the VA is not primary source of care will be excluded.
Pharmacists from the Denver VA Medical Center and who work in the anti-coagulation clinics were eligible.
Data analysis plan: This study used an iterative, inductive and deductive toolkit of analytical strategies drawing on field notes and memoing, qualitative content methods of analysis, and reflexive team analysis. ATLAS.ti v 6.2 (Scientific Software Development, GmbH, Berlin) was used for data organization and management during analysis.

Aim 3:
This pilot study tested relative to usual care, a patient-centered intervention to improve adherence to dabigatran among veterans newly initiated (within the past 2 months). This aim of the study wille nroll 150 patients; Intervention (n=75) versus usual care (n=75) and last for 6-months.
We will develop a pilot intervention informed by barriers/facilitators identified in interviews. The intervention will include: 1) patient education, provided on a regular ongoing basis; 2) tele-monitoring via interactive voice response (IVR) technology with routine educational and refill reminder calls; and 3) pharmacy service follow-up to ensure patients have refilled oral anticoagulants and address adherence/refill.
Pharmacy technicians and pharmacists on the clinical pharmacy service will deliver the intervention.
Setting and patients: The pilot will be conducted at the Denver VA Medical Center. Patients will be included if they have been recently started on dabigatran (i.e., within the past 2 months) for atrial fibrillation. Patients will be excluded for the following reasons: 1) lack of telephone/cell phone; or 2) VA is not primary source of care.

Pilot intervention study design: Patients newly started on dabigatran for atrial fibrillation will be screened and recruited by the staff pharmacists during an in person visit. Patients will be consented randomized to the intervention or usual care in a 1:1 fashion, using a computer generated algorithm.
Outcomes:
1. Gaps between prescription refills for dabigatran
2. Number of IVR calls delivered to patients
3. Number of pharmacy service contacts with patient
Interviews and a survey will be conducted with patients and providers: 3-6 months post intervention to further evaluate intervention. We will focus on components that were effective, not effective, and aspects that could be improved upon. This will provide further information to refine the intervention, and help develop accurate measures of implementation effectiveness for a potential larger study if pilot is demonstrated to be effective.

FINDINGS/RESULTS:
In June 2013 a project modification was submitted to continue the Dabigatran study, extend intervention from 3 to 6 months, and include and enroll all patients on new anti-coagulants including Rivaroxaban and Apixaban. Five additional patients were enrolled; three randomized to the intervention group and two to control group.

Throughout the whole study 12 patients were enrolled; 6 randomized to intervention and 6 to control

5/6 intervention patients enjoyed study and felt calls were helpful to remind them to take their medications

4/6 control patient felt refill reminder/education calls would be helpful for them to appropriately take their medications

Patients had the following suggestions: provide more information about prescribed medications, calls should specifically state the medication due for refill, more frequent pharmacy contact, and provide more than a 30 day supply of medications

Total medication gap days for patients who received the educational/refill reminder calls for 3 months was 43 for the 3 intervention patients and 51 for the 4 control patients.

Total medication gap days for patients who received the educational/refill reminder calls for 6 months was 41 for the 3 intervention patients and -5 for the 2 control patients.

Through this study and the qualitative interviews, we found that intervention participants enjoyed the IVR calls however did not feel they needed the reminders to take their medications as they shared they already had good medication adherence. Despite their self-reported adherence, they had a greater amount of gap days compared to the control group. It does not appear, through our analyses, that the intervention improved medication adherence among the patients randomized to the intervention; however, the findings were limited by a small sample size.

IMPACT:
Through the study and qualitative interviews, we found that the intervention participants enjoyed the IVR calls, however did not feel they needed reminders to take their medications as they shared they already had good adherence. Despite their self-reported adherence, intervention patients had more gap days compared to the control group. It does not appear, through our analyses, that the intervention improved medication adherence among the patients randomized to the intervention; however the findings were limited by a small sample size.

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External Links for this Project

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PUBLICATIONS:

Journal Other

1. Shore S, Carey E, Turakhia M, Jackevicius CA, Cunningham F, Pilote L, Baron A, Grunwald G, Bradley SM, Maddox TM, Rumsfeld JS, Varosy PD, Ho M. Patterns of Adherence to Dabigatran and its Association with Outcomes. [Abstract]. Circulation. 2013 Nov 26; 128(22 Suppl):A16864. [view]

DRA: Cardiovascular Disease
DRE: Treatment - Preclinical
Keywords: none
MeSH Terms: none