Background Pharmacist-led anticoagulation management services (AMS) for direct oral anticoagulants (DOACs) reduce prescribing errors and enhance adherence, but have not demonstrated lower rates of stroke or bleeding compared to usual care, and their cost-effectiveness is unknown. We evaluated four anticoagulant strategies for patients with atrial fibrillation initiating therapy: warfarin AMS, DOAC usual care, DOAC population management tool (PMT), and DOAC AMS.

Methods We developed a Markov model with monthly cycles simulating lifetime risk of ischemic stroke, major bleeding, death, disability, and costs from a US healthcare sector perspective. Costs and outcomes were discounted 3% annually. Model probabilities were derived from a prior Kaiser Permanente comparative-effectiveness analysis. Other inputs from published literature and national data. Primary outcomes were direct healthcare costs (2025 USD), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). Sensitivity analyses assessed parameter uncertainty.

Results DOAC-based strategies yielded greater QALYs than warfarin AMS and were cost-effective at standard willingness-to-pay thresholds. Compared with warfarin AMS, DOAC usual care gained 0.4 QALYs (ICER $89,200/QALY), DOAC PMT gained 0.6 QALYs (ICER $66,700/QALY), and DOAC AMS gained 0.6 QALYs (ICER $64,500/QALY). DOAC usual care and DOAC PMT were extendedly dominated by DOAC AMS. At $120,000/QALY, DOAC AMS was preferred in 50.4% of probabilistic iterations, DOAC PMT in 36.3%, DOAC usual care in 11.0%, and warfarin AMS in 2.3%. Results were most sensitive to DOAC program effectiveness and DOAC costs.

Conclusions Pharmacist-led DOAC management is cost-effective compared with warfarin AMS for AF patients. These findings support broader adoption of structured DOAC management programs to optimize anticoagulation therapy.

JBK is supported by grant funding from the Agency for Healthcare Research and Quality; the National Heart, Lung, and Blood Institute; and the National Institute on Aging. KR has received support from the National Heart, Lung, and Blood Institute (R01HL142834) and CSL Behring, LLC. JA is supported by grant funding from the National Heart, Lung, and Blood Institute (R01HL142834) and AstraZeneca and Bayer. DMW is supported by grant funding from the Agency for Healthcare Research and Quality (R18 HS27960) PMH is supported by grants from the National Heart, Lung, and Blood Institute, the Veterans Affairs HSR&D, and University of Colorado School of Medicine. He had a research agreement with Bristol-Myers Squibb through the University of Colorado focused on atrial fibrillation. He serves as the Deputy Editor for Circulation: Cardiovascular Quality and Outcomes. BKB was supported by National Heart, Lung, and Blood Institute (K01HL140170). All other authors have no relationships to disclose.

This work was funded by a grant (R18HS026156) from the Agency for Healthcare Research and Quality (AHRQ).

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Kaiser Permanente's interregional Institutional Review Board (KPiIRB)

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I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

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No individual-level patient data were used in this analysis. The analysis was conducted using a decision-analytic Markov model populated with parameters derived from published literature and publicly available sources. All model inputs are reported in the manuscript and/or supplementary materials.