In a recent study published in JAMA Network Open, researchers compared outcomes related to three direct oral anticoagulant (DOAC) care models to prevent anticoagulation-associated adverse effects among adult atrial fibrillation (AF) patients.
Study: Association of Direct Oral Anticoagulation Management Strategies With Clinical Outcomes for Adults With Atrial Fibrillation. Image Credit: NakharinT/Shutterstock.com
DOAC management services aim to prevent adverse drug events in AF patients; however, there is limited evidence to demonstrate improvements in stroke and bleeding outcomes. Although DOACs have a favorable safety profile, their clinical management differs from warfarin.
Despite debate in anticoagulation stewardship circles, whether direct oral anticoagulant (DOAC) stewardship programs are needed remains unsatisfactorily answered.
About the study
In the present retrospective cohort pharmacoepidemiologic study, researchers investigated whether system-level DOAC treatment management services could improve anticoagulation-associated outcomes (i.e., stroke, bleeding, and mortality) among patients initiating direct oral anticoagulants under different models for DOAC care.
The study comprised 44,746 AF patients above 18 who were initiated on oral anticoagulants (warfarin or DOAC) between 1 August 2016 and 31 December 2019 in three Kaiser Permanente (KP) locations, i.e., Colorado, Northwest, and South California.
Every KP area utilized an anticoagulation management service for managing warfarin therapy but used different DOAC care approaches: (i) usual-type care (UC) provided by attending clinicians, (ii) usual care and an additional computerized population management tool (PMT) model or (iii) pharmacist-managed anticoagulation management service care.
Usual care recipients did not receive a system-level direct oral anticoagulant management service. In the usual care plus PMT model, the prescribing health physician managed all aspects of direct oral anticoagulant usage, and three pharmacists specializing in anticoagulation management received reports every week from automated PMTs in the electronic medical records (EMRs), which identified individuals with probable DOAC-associated issues based on laboratory and dispensing-related EMR data.
The anticoagulation management services (AMS) cohort comprised individuals prescribed a DOAC and proactively enrolled in the AMS led by the pharmacist managing warfarin treatment.
Patients not initially referred to the AMS by their clinician were identified for enrollment using electronic prescription and pharmacy dispensing data. Data were analyzed between August 2021 and May 2023 following propensity score matching (PSM) using the inverse probability of treatment weighting (IPTW) approach to calculate the adjusted hazard ratios (aHR).
Covariates for data adjustment included age, sex, comorbidities, educational level, income, ambulatory blood pressure (BP) readings, and healthcare visits within six months to one year before the index date.
DOAC models were initially compared indirectly with warfarin medication as the common comparator among all regions, followed by a direct comparison across KP regions (post hoc analysis).
The study participants were followed until a study outcome occurred (a composite measure of intracranial hemorrhage, thromboembolic stroke, other major causes of bleeding, or mortality), termination of Kaiser Permanente membership, or 31 December 2020.
Medication dispensing information from pharmacies was used to track DOAC initiation (rivaroxaban, dabigatran, edoxaban, and apixaban).
The team excluded individuals with a positive history of oral anticoagulant usage in the previous six months; those who were dispensed multiple oral anticoagulants on the index date; individuals who died before the index date; those with less than a year of KP membership before the index date; and those who were not diagnosed with AF within a year before a week after the index date.
In total, 44,746 individuals were included: 6,182 in the usual care cohort (3,297 and 2,885 DOAC and warfarin recipients, respectively), 33,625 individuals in the usual and PMT care cohort (21,891 and 11,734 DOAC and warfarin recipients, respectively), and 4,939 in the anticoagulation management service care cohort (2,089 and 2,850 DOAC and warfarin recipients, respectively).
The mean age of the study participants was 73 years; 56% were men, and 67% were non-Hispanic Whites. Dabigatran was the most frequently used direct oral anticoagulant across all care models.
A 3.0 median score was observed for the CHA2DS2-VASc [heart failure, blood pressure elevation above normal, age ≥75.0 years, stroke, diabetes, vascular disease, 65 to 74 years of age, and female gender], which was well-balanced following inverse probability of treatment weighting.
Over two years of follow-up (median), AF outcomes in the usual care and PMT or pharmacist-managed anticoagulation management service care models did not differ significantly from usual care recipients.
The annual incidence rates for the composite measure were 5.40% and 9.10% for the DOAC and warfarin among usual care recipients, respectively.
The corresponding rates were 6.10% and 11% in the usual care plus PMT cohort, respectively, and five and eight percent in the anticoagulation management service cohort. The composite measure aHRs comparing DOAC versus warfarin therapy were 0.9, 0.9, and 0.8 in the usual care cohort, the usual care plus PMT cohort, and the anticoagulation management service cohort, respectively.
The posthoc analysis yielded an aHR of 1.1 for the usual care plus PMT cohort versus the usual care cohort and 0.9 for the AMS cohort versus the UC cohort. DOAC management services significantly reduced patients' risk of adverse outcomes compared to warfarin therapy.
In regions using system-level DOAC management services, DOAC therapy was better than warfarin therapy and had similar clinical trial outcomes. However, the UC approach had better outcomes than anticipated, indicating that the rationale for implementing system-scale DOAC care may not be ideal.
Overall, the study findings showed no appreciably better outcomes for AF patients receiving DOAC managed by the usual care plus PMT or the AMS care models than usual care.
The most appropriate approach to direct oral anticoagulant management remains unclear, warranting future research, including randomized clinical trials (RCTs) and cost-effectiveness analyses.