Wide Variability in Medication Adherence among Patients with Atrial Fibrillation

Research indicates that, despite the relative simplicity of dabigatran regimens, physicians and pharmacists must follow up with patients repeatedly to maximize the chances they’ll adhere to prescriptions.

Older blood thinners such as warfarin specifically required heavy follow-up in the form of routine blood tests and dose adjustments, but the rigid dosing guidelines for novel oral anticoagulants such as dabigatran (Pradaxa) offered clinicians hope of a much less labor-intensive way to medicate patients with atrial fibrillation (AF).

Researchers decided use data from the Veterans Health Administration (VHA) to see how much labor was actually required by studying how follow-up protocols affected dabigatran adherence.

The study team compared data from 67 VHA facilities with at least 20 patients using dabigatran for nonvalvular AF between 2010 and 2012. Then, team members reviewed practices and each site and noted how many used adherence-boosting strategies such as appropriate patient selection (31 sites), pharmacist-led education (30 sites), and pharmacist-led monitoring (28 sites).

In all, the study used data from 4,863 patients (or about 51 patients per site). The median proportion of patients at any given site who took 80% of their dabigatran each month and thus qualified as “adherent” was 74%, but adherence differed significantly among the sites.

The interquartile compliance range was 66% to 80%, and, after multivariable adjustment, the study team found that dabigatran adherence varied across sites by a median odds ratio of 1.57.

Moreover, the researchers wrote in the Journal of the American Medical Association, “Specific pharmacist-based activities were associated with greater patient adherence to dabigatran.”

Looking just at raw numbers, the proportion of patients who took their medicine was higher at sites performing appropriate selection (75% vs. 69%), education (76% vs. 66%), and monitoring (77% vs. 65%).

Multivariable adjustment eliminated the significance of the association between pharmacist-led education and dabigatran adherence (relative risk [RR], 0.94; 95% CI, 0.83-1.06), but the other 2 relationships survived the analysis.

Appropriate patient selection (RR, 1.14; 95% CI, 1.05-1.25), and provision of pharmacist-led monitoring (RR, 1.25; 95% CI, 1.11—1.41) were both associated with better patient adherence.

What’s more, the researchers found, longer duration of monitoring and collaboration with clinicians to provide more intensive care to non-adherent patients also improved adherence.

“Prior studies have described variation in patient performance on warfarin across sites further highlighting the importance of management strategies in improving patient performance to anticoagulants,” the researchers wrote.

“Our results highlight the importance of selecting patients and monitoring strategies to translate the efficacy of target-specific oral anticoagulants in randomized trials to clinical practice… These findings suggest that such site-level practices provide modifiable targets to improve patient adherence to dabigatran as opposed to patient characteristics that frequently cannot be modified.”

The study team’s finding is potentially important because previous research has found that patients who take less dabigatran than prescribed face an increased risk of both stroke and death.

The potential for non-adherence is generally considered a major weakness of novel oral anticoagulants (NOACs).

The need to monitor warfarin efficacy quickly draws clinician attention to non-compliant patients, but NOACs can be used (and generally are used) without any comparable early-warning system.

The need to take many NOACs twice daily is another hurdle to compliance, as is the relatively high cost of the medications. (Many studies indicate that patients try to save money by trying to make expensive medications last longer than they should).