Managing Direct Oral Anticoagulants – What’s Our Role?

Many clinicians are questioning the role pharmacists should play in anticoagulation therapy management as direct oral anticoagulants (DOACs) increasingly replace warfarin for a variety of indications. When we say “anticoagulation clinic” most of us envision a group of practitioners — often pharmacists — delivering coordinated care, providing ongoing patient education, and using laboratory data to make adjustments in warfarin doses. Unlike warfarin, DOACs do not require routine laboratory monitoring — leading some to speculate how much longer anticoagulation clinics will be needed. Moreover, DOACs do not have a laundry list of clinically important drug-drug and drug-food interactions that can impact therapy. Perhaps there really isn’t much for pharmacists to do!  DOACs, however, have a relatively short half-life which puts patients at higher risk of thrombotic events when doses are missed. Anything less than optimal adherence to DOACs has been shown to increase the risk of all-cause mortality and stroke [HR 1.13, 95% CI 1.07–1.19 per 10% decrease in proportion of days covered (PDC)].¹ In addition to reinforcing adherence with DOACs, ongoing patient management may be needed to address changes in health status, altered renal function, and drug-drug interactions.  Although the list is smaller, DOACs are not free from drug interactions! With the growing use of DOACs, pharmacists may still be needed in rebranded “thrombosis clinics” to provide ongoing monitoring to patients taking a variety of antithrombotic agents – not just warfarin.²

Models of practice for  managing patients on DOACs have yet to be established and the precise role that pharmacists should play is largely unexplored. One single-center study documented no difference in medication adherence at 3 months between a cohort of patients taking dabigatran who received education and short-term follow-up in an anticoagulation clinic vs. those who did not.³  This study suggests that patient education and short-term follow-up may not be sufficient. Other aspects of patient care such as screening candidates to be certain DOACs are appropriate, monitoring for therapy-related complications, and addressing cost-related issues may need to be considered. Additionally, the pharmacists’ impact on patients’ quality of life and satisfaction haven’t been examined.

A study by Supriya Shore and colleagues took a closer look at anticoagulation practice patterns and dabigatran adherence beyond a single-center.⁴  The study used a mix-methods design and examined medication adherence in relation to variations in therapy management practices between Veterans Health Administration (VHA) patient care sites. Phone interviews were conducted to identify how patients taking dabigatran were managed at each site. Then, content analysis methods were used to develop general descriptors for the strategies the sites employed.  Identified strategies related to patient selection, patient education, and patient monitoring. Appropriate patient selection focused on confirming an appropriate indication and lack of contraindications to dabigatran as well as an assessment of adherence to other medications prior to starting dabigatran. Patient education included strategies such as a mandatory pharmacist-led education session prior to dispensing dabigatran. Finally, patient monitoring included ongoing adverse event and adherence monitoring by a pharmacist – either face-to-face or via telephone.

The study cohort included 4863 patients who received dabigatran for non-valvular atrial fibrillation for more than 30 days and were managed at 67 VHA sites that had at least 20 patients taking dabigatran between 2010 and 2012. In those sites were a practice assessment was completed (n=41 sites with 2985 patients), 98% (n=40) utilized pharmacists to review indications for and contraindications to dabigatran, 73% (n=30) utilized pharmacists to lead patient education prior to dispensing, and 68.3% (n=28) had pharmacist-provided monitoring for adverse events and adherence. In order to determine characteristics associated with improved adherence, sites with an average proportion of days covered (PDC) less than the median PDC (74%) were classified as low-performing sites (n=18 sites with 1157 patients). Conversely, those sites with an average PDC greater than the median were classified as high-performing sites (n=23 sites with 1828 patients). Notably, high-performing sites had a higher proportion of patients who were white and lower proportion who had chronic kidney disease when compared to lower-performing sites.

The primary outcome was the proportion of patients at each site who were adherent to dabigatran, defined as a PDC of at least 80%. The overall mean proportion of patients who were deemed adherent was 72% but the proportion of patients at individual sites who were adherent ranged from a low of 42% to a high of 93%. Medication adherence was higher in those sites where appropriate patient selection and adherence monitoring was performed; however, pharmacist-led patient education prior to initiation of dabigatran was not associated with a higher proportion of patients adherent with therapy (Table 1). Patient monitoring at 3, 6 and 12 months were all found to be associated with improved adherence (Table 1). Lastly, the method of contact (phone vs face-to-face) was not associated with a difference in adherence in a multivariate model.

Table 1.  Association Between Patient Management Strategies and Proportion of Patients Adherent to Dabigatran

*Following multivariate adjustment

The study has several limitations such as use of PDC as a marker for adherence. PDC only assesses how often prescriptions are filled and does not directly measure whether the patient actually took the medication. Additionally, PDC was assumed to correlate to patient outcomes such as thromboembolic events.  To make a firm conclusion that these practices truly make a difference, a direct assessment of strokes and other important outcomes such as bleeding events and adverse effects is needed. Further, the study does not directly compare different practice models. Although these results give us a general sense of “what” strategies improved adherence, they are short on specifics – the “how” and “when.”  Additional data would help to better define the role of the pharmacist and could be used to justify pharmacy services for continued management of DOACs. Lastly, the study did not explore the content or extent of the patient education provided. Further study is needed to determine what instructional methods work best.  It is clear, however, that patient education alone is not sufficient.  Ongoing patient monitoring is the key.

Although this study may not have all the answers, it does reveal the importance of patient selection and ongoing patient monitoring – potentially key roles for pharmacists. It is particularly noteworthy that a longer duration of patient monitoring appeared to be associated with greater improvements in adherence (Table 1). This suggests pharmacists should manage DOAC therapy well beyond the initial screening, patient education, and adverse event monitoring phase. Patients may need ongoing support and feedback in order to achieve optimal outcomes. Future studies should examination the frequency of patient contact and the duration of patient monitoring needed. Some patients with excellent self-management behavior may not benefit from long-term monitoring – but others may need ongoing TLC. Does this study provide us with enough evidence to justify a patient screening and ongoing DOAC monitoring service? How frequently should we interact with patients on DOACs?  Are face-to-face encounters needed?  Tell use what you think.