Pharmacists May Help Ameliorate Substantial Variation in Dabigatran Adherence
For patients with nonvalvular A-fib treated with dabigatran within the VA healthcare system, there is considerable variability in adherence across sites, according to a study published in the April 14, 2015, issue of the Journal of the American Medical Association. Adherence is better at centers where pharmacists are involved in determining whether the drug is appropriate for individual patients and in monitoring compliance with treatment.
“I think these findings could be a bit disruptive because they challenge our framework of how we’re delivering care around [novel oral anticoagulants (NOACs)],” study author Mintu P. Turakhia, MD, MAS, of the VA Palo Alto Health Care System (Palo Alto, CA), told TCTMD in a telephone interview.
“We’re prescribing them. We might spend a few minutes talking to our patients about them in the office; maybe our nurses do that,” he said. “Clearly that’s not good enough, and we’re hoping that this [study] will allow greater discussion on how to [deliver] these drugs.”
Dr. Turakhia and colleagues looked at data from 67 VA sites that had at least 20 patients with nonvalvular A-fib who filled dabigatran (Pradaxa; Boehringer Ingelheim) prescriptions from October 2010 through September 2012. The study included 4,863 patients (median 51 per site). Mean patient age was about 71 years, and 98% were male. The researchers also interviewed 47 pharmacists from 41 sites about procedures for managing patients taking dabigatran.
Those interviews uncovered 3 main site-level practices for managing dabigatran use:
- Appropriate patient selection by pharmacists based on VA guidelines, including an assessment of indications/contraindications and of adherence to other medications before starting treatment
- Mandatory pharmacist-led patient education before dispensing dabigatran for the first time and at each patient-pharmacist contact
- Pharmacist-led adverse event and adherence monitoring
Appropriate patient selection was performed at 31 sites, pharmacist-led education at 30 sites, and pharmacist-led monitoring at 28 sites.
Adherence Highly Variable, Linked to Site-Level Practices
The median proportion of patients deemed adherent was 74%, although that figure ranged from 42% to 93% across sites. Treatment at a site with adherence below vs above the median was associated with a relative 57% increase in the odds of being nonadherent after multivariate adjustment.
Unadjusted dabigatran-adherence rates were higher at sites using appropriate patient selection (75% vs 69%), pharmacist-led monitoring (77% vs 65%), and pharmacist-led education (76% vs 66%), but the difference was not significant for education efforts after adjustment (table 1).
Both longer duration of patient monitoring and provision of more intensive care to nonadherent patients in collaboration with clinicians were associated with improved adherence. However, the likelihood of being adherent was not influenced by the involvement—or lack thereof—of anticoagulation clinics or by the method of contacting patients.
Warfarin-Like Infrastructure Needed for NOACs?
Before NOACs hit the market with the approval of dabigatran in 2010, warfarin was the go-to treatment for stroke prevention in A-fib. One of the primary purported advantages of NOACs over warfarin is that they do not require periodic testing of the anticoagulant effect.
However, adherence to the newer agents has been shown to be worse in everyday practice than in the clinical trials supporting their approval. And poorer adherence was linked to greater risks of stroke and death in a previous VA study by Dr. Turakhia and colleagues.
The findings of the current study suggest that “site-level practices provide modifiable targets to improve patient adherence to dabigatran as opposed to patient characteristics that frequently cannot be modified,” they write.
According to Dr. Turakhia, pharmacist-led management of patients taking dabigatran is uncommon in the United States. The next step, he said, should be to expand the purview of anticoagulation clinics set up to monitor warfarin to include management of NOACs. Incentives and penalties are needed to motivate healthcare systems to change, he asserted, noting that reimbursement currently exists only for monitoring patients on warfarin—not the newer drugs.
When asked whether randomized data demonstrating the effectiveness of managing NOACs in such a way are needed before implementing system-wide changes, Dr. Turakhia said, “I think this [study] is compelling enough.”
He and his colleagues are planning a cluster-randomized trial to evaluate whether pharmacist-led management of NOACs makes a clinical impact. But Dr. Turakhia said that even without its findings, putting all of the pieces together—ie, adherence is suboptimal in the real world and varies across sites, poor adherence is tied to worse outcomes, and modifiable site-level factors are associated with better adherence—“tells you… that you need to at least try this. I’m not sure you need a trial to do something that just makes good sense.”
Pharmacists Not the Only Option
However, Dr. Turakhia also acknowledged that it is unknown whether monitoring and follow-up by pharmacists is necessary for improving adherence, suggesting that clinicians might be able to handle it. “But I’m not so sure of that, because we already know that anticoagulation clinics do a better job with warfarin—and those are usually run by pharmacists—than doctors’ offices,” he said.
Management might not always have to include a human being either, he added, pointing to the potential for using mobile health interventions and automated systems. Those ideas can be tested, but “the point we’re making is that usual care seems to not be good enough,” Dr. Turakhia said.
Shore S, Ho PM, Lambert-Kerzner A, et al. Site-level variation in and practices associated with dabigatran adherence. JAMA. 2015;313:1443-1450.
Dr. Turakhia reports serving as a consultant to Medtronic, Precision Health Economics, and St. Jude Medical and receiving support from a Career Development Award from VA Health Services Research & Development, an America Heart Association National Scientist Development Grant, and a Gilead Sciences Cardiovascular Research Scholars Program award.