Formulary Fit: Preparing Pathways and Protocols for a New Class of Antithrombotic Therapy

This content was independently produced by Pharmacy Times in partnership with Bayer HealthCare.

Asundexian (Sunharbo; Bayer HealthCare) brings a practical question to pharmacy and therapeutics (P&T) committees: How should a factor XIa inhibitor be incorporated into secondary stroke prevention? In May 2026, Bayer announced FDA acceptance of its new drug application and priority review designation for secondary prevention after noncardioembolic ischemic stroke or transient ischemic attack (TIA), and on November 9, 2026, it received approval from the FDA.^1,2 Hospitals can begin preparing an evidence review and implementation plan, with prescribing criteria finalized against FDA-approved labeling. American Society of Health-System Pharmacists (ASHP) guidance supports a review that integrates clinical evidence, medication safety, costs, implementation, and ongoing evaluation.³

Define the Clinical Role

The starting point is the treatment strategy evaluated in OCEANIC-STROKE (NCT05686070). The phase 3 trial randomly assigned 12,327 patients to asundexian 50 mg once daily or placebo, both added to planned single or dual antiplatelet therapy. Over a median of approximately 19 months, ischemic stroke occurred in 6.2% vs 8.4% of participants, respectively (cause-specific HR, 0.74; 95% CI, 0.65-0.84; P < .001). Major bleeding occurred in 1.9% vs 1.7% of participants (cause-specific HR, 1.10; 95% CI, 0.85-1.44).⁴ These findings support the consideration of an additional prevention strategy, but they do not establish reduced bleeding as an outcome or eliminate uncertainty about bleeding risk.

For formulary purposes, this is an addition to antiplatelet therapy. OCEANIC-STROKE did not compare asundexian with apixaban or rivaroxaban.³ In the separate OCEANIC-AF trial (NCT05643573), asundexian was less effective than apixaban for preventing stroke or systemic embolism in patients with atrial fibrillation (AF).⁵ P&T committees should therefore avoid therapeutic interchange with established anticoagulants and evaluate each factor XI/XIa–directed agent by its own evidence and indication.

Establish an Eligibility Pathway

The formulary monograph should distinguish the population studied from the eventual approved population. OCEANIC-STROKE enrolled adults within 72 hours of a noncardioembolic ischemic stroke with a National Institutes of Health Stroke Scale score of 15 or lower, or a high-risk TIA with an ABCD² score of 6 or 7. Participants also needed a nonlacunar infarct, a qualifying history of atherosclerosis, or evidence of atherosclerotic plaque on cerebrovascular imaging.⁴ These findings should not be generalized automatically to every patient with stroke or TIA.

Pharmacy and the stroke service should agree on who confirms eligibility, initiates treatment, and reassesses the regimen when the presumed stroke mechanism changes. The pathway should require documentation of stroke mechanism, event timing, antiplatelet treatment, bleeding history, and any separate indication for anticoagulation. In OCEANIC-STROKE, study treatment was stopped and open-label anticoagulation started when AF or another anticoagulation indication emerged.⁴ A local protocol should specify how such patients receive prompt specialist reassessment.

Build the Complete Regimen Into the Order Set

The electronic order should link asundexian to its intended indication and accompanying antiplatelet plan. Existing stroke guidance recommends short-term dual antiplatelet therapy for select patients, with eligibility and duration determined by the clinical setting.⁶ The order set should identify each antiplatelet agent, its indication, and any planned stop date. Adding another antithrombotic should trigger review of the entire regimen rather than inadvertently extending dual antiplatelet therapy.

Duplicate-therapy alerts will require careful design. They should prompt review of concurrent anticoagulants while recognizing that concomitant antiplatelet treatment was part of the stroke trial. Patients with additional coronary or vascular indications may need individualized review. The trial protocol allowed short-term venous thromboembolism prophylaxis with heparin or low-molecular-weight heparin.⁴ Pharmacists should define how prophylaxis orders will be reviewed without assuming that asundexian substitutes for prophylaxis.

The trial dose should inform the monograph, but the commercial order set must follow the approved dose and administration instructions. Before activation, pharmacy should verify labeling for organ dysfunction, missed doses, swallowing limitations, and feeding-tube administration. The final trial protocol permitted crushed tablets, including administration through a feeding tube.⁴ Commercial instructions should be verified before these options are built into orders.

Prepare Interaction and Emergency Guidance

Interaction screening deserves specific attention. In healthy-volunteer studies, itraconazole and verapamil increased asundexian exposure, whereas carbamazepine reduced it.⁷ These pharmacokinetic findings support targeted medication review, but they do not independently establish a clinical dose-adjustment algorithm. Pharmacy should reconcile the final label with the interaction database and build actionable alerts for affected drugs.

Before implementation, a multidisciplinary group should agree on baseline laboratory assessment, follow-up responsibilities, and evaluation of suspected bleeding. A practical assessment can include a complete blood count and renal and hepatic function, with subsequent monitoring tailored to labeling and patient circumstances. These are proposed local safeguards, not trial-proven monitoring intervals.

Emergency, stroke, hematology, laboratory, and procedural teams should also establish an accessible plan for major bleeding, urgent surgery, and a new acute stroke during treatment. The plan should address documentation of the last dose, interpretation and limitations of available coagulation tests, consultation pathways, and available hemostatic options. Drug-specific evidence and labeling should guide interruption and resumption decisions, and protocols should not presume that another anticoagulant’s reversal strategy applies.

Assess Value and Reassess Use

Budget impact should reflect the strategy studied: adding therapy to antiplatelet treatment.⁴ P&T review should consider the locally eligible population, acquisition cost, outpatient coverage, and the resources required for prescribing and follow-up.³ Any estimates of avoided strokes should use a defined time horizon and transparent assumptions. The economic model should not assume savings from fewer major bleeding events on the basis of OCEANIC-STROKE alone.⁴

If adopted, an early medication-use evaluation should examine indication concordance, unintended antithrombotic overlap, clinically important interactions, treatment interruptions, bleeding, and recurrent ischemic events, consistent with ASHP’s medication-use evaluation framework.³ These observations can identify implementation problems, although local event rates will not reproduce a randomized comparison. Assigning responsibility for reassessment as labeling and evidence evolve will help P&T committees translate a promising trial result into a clearly defined place in care.

REFERENCES

1. Bayer granted priority review by U.S. FDA for asundexian in patients after a non-cardioembolic ischemic stroke or transient ischemic attack. News release. Bayer. May 19, 2026. Accessed September 21, 2026. https://www.bayer.com/en-us/united-states/news-and-stories/2026/asundexian-in-patients-after-a-non-cardioembolic-ischemic-stroke

2. FDA approves first factor Xla inhibitor to help prevent stroke in certain adults at high risk. News release. FDA. November 9, 2026. Accessed November 10, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-first-factor-xla-inhibitor-help-prevent-stroke-certain-adults-high-ris

3. Ciccarello C, Leber MB, Leonard MC, et al. ASHP guidelines on the pharmacy and therapeutics committee and the formulary system. Am J Health Syst Pharm. 2021;78(10):907-918. doi:10.1093/ajhp/zxab080

4. Sharma M, Dong Q, Hirano T, et al; OCEANIC-STROKE Investigators. Asundexian for secondary stroke prevention. N Engl J Med. 2026;394(15):1467-1479. doi:10.1056/NEJMoa2513880

5. Piccini JP, Patel MR, Steffel J, et al; OCEANIC-AF Steering Committee and Investigators. Asundexian versus apixaban in patients with atrial fibrillation. N Engl J Med. 2025;392(1):23-32. doi:10.1056/NEJMoa2407105

6. Prabhakaran S, Gonzalez NR, Zachrison KS, et al. 2026 guideline for the early management of patients with acute ischemic stroke: a guideline from the American Heart Association/American Stroke Association. Stroke. 2026;57(8):e316-e436. doi:10.1161/STR.0000000000000513

7. Kanefendt F, Brase C, Jungmann N, Fricke R, Engelen A, Schmitz S. Pharmacokinetics of asundexian with combined CYP3A and P-gp inhibitors and an inducer: target in vitro and in vivo studies. Br J Clin Pharmacol. 2024;90(4):1036-1049. doi:10.1111/bcp.1598