Objective. To assess site level adherence to dabigatran among patients with atrial fibrillation and to determine if specific practices at the site level are associated with adherence.
Design. Mixed-methods study involving retrospective quantitative and cross-sectional qualitative data.
Setting and participants. 67 Veterans Health Administration sites with 20 or more patients with dabigatran prescription for nonvalvular atrial fibrillation between 2010 and 2012 were included. Among these sites, 41 sites participated in an inquiry about practices related to dabigatran use. A total of 47 pharmacists among the 41 sites were interviewed. The investigators identified from the interviews 3 specific practices related to dabigatran use: appropriate patient selection (review of indications, contradictions, and prior adherence to other medications), pharmacist-driven patient education, and pharmacist-led adverse event and adherence monitoring. Sites were characterized as having adopted these specific practices or not, based on the interviews.
Main outcome measure . Dabigatran adherence defined by proportion of days covered (ratio of days supplied by prescription to follow-up duration) of 80% or more. Site level variance in dabigatran adherence among the 67 sites were described. Site level adherence was adjusted by patient level factors and site level factors. The association between site level practice and adherence was examined with Poisson models using generalized estimate equation to account for clustering of patients within sites.
Main results . A total of 67 sites with 4863 patients with prescriptions of dabigatran for atrial fibrillation were included in the analysis. There was wide variation among sites on adherence rate, with a range of 42% to 93% (median, 74%). The sites were categorized as high performing if their site level adherence rate was at least 74%. Among the 41 sites that participated in the qualitative study that defined exposure variables, appropriate patient selection was performed at 31 sites, pharmacist-led education was provided at 30 sites, and pharmacist-led monitoring at 28 sites. There was variation in the duration of monitoring among sites, with 18 of 28 monitoring for 3 to 6 months while the rest of the sites monitor indefinitely. Site level practices differed between low and high performing sites, with high performing sites more likely to have adopted appropriate patient selection with review of adherence (83% vs. 65% in low-performing sites), have pharmacist-driven education (83% vs. 59%), and have pharmacist-led adverse event monitoring (92% vs. 35%). After adjustment for patient level and site level characteristics, the association between adherence and appropriate patient selection (adjusted risk ratio [RR], 1.14; 95% confidence interval [CI], 1.05–1.25) and pharmacist-led adverse event monitoring (RR, 1.25; 95% CI, 1.11–1.41) remained.
Conclusion. There is wide variability in dabigatran adherence among patients with atrial fibrillation at different VA sites. Site level pharmacist-based practices are associated with the level of adherence at the sites.
Studies have demonstrated that in a clinical trial setting, dabigatran is as effective as warfarin in stroke prevention among patients with atrial fibrillation and is associated with a lower risk of major hemorrhage . However, outside of clinical trials, effectiveness of a treatment regimen is highly related to whether treatment is adhered to. In contrast with warfarin treatment, where treatment adherence is regularly tracked through monitoring of blood levels and clinic visits, dabigatran does not require monitoring and thus, adherence to dabigatran may not be monitored. A recent study finds that poorer adherence likely contributes to increased risk of stroke and death among patients on dabigatran . The current study examines the variation in adherence rates on a site level and identifies factors that are associated with better adherence. The findings suggest that better patient selection through examination of prior adherence to warfarin and other medications and pharmacist-led adverse event and adherence monitoring are practices that are associated with better adherence. These are potentially important findings that may impact care for patients with atrial fibrillation.
These results need to be interpreted cautiously because of the limitations of the observational study design. Several factors need to be considered when interpreting the study findings. First, despite the VA being a comprehensive system of care, veterans often use care outside of the VA, including obtaining medications outside of VA . Because of the prevalent concurrent use of care outside of VA, examining adherence to medication with only VA records may be incomplete and may erroneously categorize patients as low adherence. Second, the number of patients on dabigatran per facility is rather small and quite variable as well, with some sites that have very few number of patients. Although the investigators have excluded sites with fewer than 20 patients on dabigatran, the variability in the use of dabigatran may reflect site-specific factors, some of which may affect patient selection on the site level, that ultimately may affect outcome. Finally, the interview of pharmacist at each site may reflect the view of one to two pharmacists at each site, and thus may not truly reflect practices at the site throughout the period where patients were selected and outcomes defined.
Applications for Clinical Practice
Although it is tempting to conclude that instituting the pharmacist-based activities in patient selection and adverse event monitoring will lead to better adherence to dabigatran and thus improved patient outcomes, considering the limitations in the study a follow-up intervention study where sites are randomized to institute-specific practices for dabigatran use will be very important to demonstrate definitively the impact of these interventions. Also, as the use of dabigatran and other novel anticoagulants become more prevalent , a follow-up study to include a larger sample of patients may also be valuable to demonstrate if the conclusions are upheld.
—William Hung, MD, MPH