Inside the OCEANIC-STROKE Trial and What Asundexian Means for the Future of Stroke Prevention

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

Ischemic stroke is a heterogeneous condition, and identifying the underlying mechanism is important for secondary prevention. For patients with noncardioembolic ischemic stroke or transient ischemic attack (TIA), antiplatelet therapy remains the foundation of antithrombotic treatment. American Heart Association/American Stroke Association guidelines recommend antiplatelet therapy rather than oral anticoagulation in this setting. Select patients receive short-term dual antiplatelet therapy, followed by long-term single antiplatelet therapy.¹

Attempts to replace aspirin with conventional anticoagulation in embolic stroke of undetermined source (ESUS) have been disappointing. In the phase 3 NAVIGATE ESUS trial (NCT02313909), rivaroxaban (Xarelto; Bayer HealthCare, Janssen Pharmaceuticals) did not improve efficacy and increased major bleeding compared with aspirin. Dabigatran was also not superior to aspirin in the phase 3 RE-SPECT ESUS trial (NCT02239120).^2,3 These findings support investigating different approaches to residual thrombotic risk, including inhibition of factor XI (FXI) and its activated form, FXIa.

Why Target Factor XIa?

FXI contributes to thrombus propagation by amplifying thrombin generation but has a comparatively limited role in normal hemostasis. Congenital FXI deficiency generally produces a milder, variable bleeding phenotype than hemophilia A or B. These observations provide a rationale for targeting FXI while potentially limiting bleeding, although clinical trials must establish that balance.⁴

Asundexian (Sunharbo; Bayer HealthCare) is an oral, direct, reversible FXIa inhibitor.^5,6 The phase 2b PACIFIC-STROKE trial (NCT04304508) evaluated it with antiplatelet therapy after noncardioembolic ischemic stroke. The trial did not meet its primary dose-response end point, which combined covert brain infarction and symptomatic ischemic stroke at 26 weeks.⁵ The subsequent phase 3 OCEANIC-STROKE trial (NCT05686070) tested asundexian 50 mg once daily using clinical ischemic stroke as its primary efficacy end point.⁶

Review of OCEANIC-STROKE

OCEANIC-STROKE was an international, randomized, double-blind, placebo-controlled trial involving 12,327 patients after noncardioembolic ischemic stroke or high-risk TIA. Patients were randomly assigned within 72 hours of symptom onset to asundexian 50 mg once daily or placebo, added to planned single or dual antiplatelet therapy. Median follow-up was approximately 19 months.⁶

The trial selected patients with a nonlacunar infarct, a qualifying history of atherosclerosis, or atherosclerotic plaque on cerebrovascular imaging. Patients with an indication for therapeutic anticoagulation were excluded. This population and treatment strategy are significant when interpreting the results: Asundexian was evaluated as an addition to antiplatelet therapy, not as a replacement for it.⁶

Ischemic stroke occurred in 384 of 6162 patients who received asundexian (6.2%) and 518 of 6165 of those receiving placebo (8.4%). The cause-specific HR was 0.74 (95% CI, 0.65-0.84; P < .001), indicating an approximately 26% lower hazard of ischemic stroke.⁶

International Society on Thrombosis and Haemostasis major bleeding occurred in 117 of 6124 treated patients receiving asundexian (1.9%) and 107 of 6130 receiving placebo (1.7%; cause-specific HR, 1.10; 95% CI, 0.85-1.44). Overall and serious adverse events were similar between groups.⁶

These findings demonstrate additional protection against ischemic stroke, although uncertainty remains regarding bleeding risk. Rates of ISTH major bleeding (1.9% vs 1.7%; HR, 1.10; 95% CI, 0.85-1.44; P = .46) and major or clinically relevant nonmajor bleeding (5.5% vs 5.0%; HR, 1.12; 95% CI, 0.96-1.30; P = .16) did not differ significantly between groups. However, safety end points were not subject to formal hypothesis testing, so these results do not establish equivalent bleeding risk or exclude a clinically meaningful increase. Bleeding was also not lower with asundexian than with antiplatelet therapy alone. At a median follow-up of approximately 19 months, the durability of benefit and longer-term safety remain uncertain.⁶

Regulatory Development and the FXI Inhibitor Pipeline

In May 2026, Bayer announced that the FDA had accepted its new drug application for asundexian and granted priority review for secondary prevention after noncardioembolic ischemic stroke or TIA.⁷ On November 9, 2026, the FDA approved asundexian 50-mg tablets for use in combination with antiplatelet therapy to reduce the risk of stroke in adults following a recent mild-to-moderate noncardioembolic ischemic stroke or a high-risk TIA.⁸ Pharmacists should distinguish the studied regimen from any eventual approved indication and prescribing instructions.

Asundexian is not the only FXIa inhibitor under investigation. The phase 3 LIBREXIA-STROKE trial (NCT05702034) is evaluating milvexian (Bristol Myers Squibb, Janssen Pharmaceuticals) vs placebo after acute ischemic stroke or high-risk TIA in patients receiving antiplatelet therapy.⁹ Other approaches to FXI inhibition include the use of monoclonal antibodies and antisense oligonucleotides.¹⁰

A systematic review published online in September 2026 pooled 3 randomized trials, including 14,239 participants from the selected dose and placebo groups. FXIa inhibition was associated with fewer ischemic strokes (risk ratio, 0.74; 95% CI, 0.66-0.84); however, the analysis included only the phase 2 doses advanced to phase 3, and OCEANIC-STROKE contributed most participants. These pooled findings do not establish a class effect or settle the question of bleeding safety.¹¹

What Does This Mean for Stroke Prevention?

OCEANIC-STROKE supports a potential additional antithrombotic approach for select patients after noncardioembolic stroke or high-risk TIA, and the data helped support asundexian’s approval. Its results should be interpreted within the trial’s eligibility criteria and background antiplatelet treatment.⁶

For pharmacists, the immediate task is to understand who was studied, the magnitude of benefit, and the limits of the safety evidence. Any future clinical role will need to reflect the regulatory decision, patient selection, and the prescribed antiplatelet regimen. The trial offers a meaningful advance in the evidence for secondary stroke prevention while leaving practical questions about implementation, longer-term safety, and other FXIa inhibitors unresolved.

REFERENCES

1. Kleindorfer DO, Towfighi A, Chaturvedi S, et al. 2021 guideline for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline from the American Heart Association/American Stroke Association. Stroke. 2021;52(7):e364-e467. doi:10.1161/STR.0000000000000375

2. Hart RG, Sharma M, Mundl H, et al. Rivaroxaban for stroke prevention after embolic stroke of undetermined source. N Engl J Med. 2018;378(23):2191-2201. doi:10.1056/NEJMoa1802686

3. Diener HC, Sacco RL, Easton JD, et al. Dabigatran for prevention of stroke after embolic stroke of undetermined source. N Engl J Med. 2019;380(20):1906-1917. doi:10.1056/NEJMoa1813959

4. Hsu C, Hutt E, Bloomfield DM, Gailani D, Weitz JI. Factor XI inhibition to uncouple thrombosis from hemostasis: JACC review topic of the week. J Am Coll Cardiol. 2021;78(6):625-631. doi:10.1016/j.jacc.2021.06.010

5. Shoamanesh A, Mundl H, Smith EE, et al. Factor XIa inhibition with asundexian after acute non-cardioembolic ischaemic stroke (PACIFIC-Stroke): an international, randomised, double-blind, placebo-controlled, phase 2b trial. Lancet. 2022;400(10357):997-1007. doi:10.1016/S0140-6736(22)01588-4

6. 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

7. 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 26, 2026. https://www.bayer.com/en-us/united-states/news-and-stories/2026/asundexian-in-patients-after-a-non-cardioembolic-ischemic-stroke

8. 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-risk

9. A study of milvexian in participants after an acute ischemic stroke or high-risk transient ischemic attack: LIBREXIA-STROKE. University of California, Davis Clinical Trials. Accessed September 26, 2026. https://clinicaltrials.ucdavis.edu/trial/NCT05702034

10. Kumbhani DJ, Armbruster AL, Cheng RK, et al. Direct oral anticoagulants in primary and secondary prevention of thrombotic events: 2026 ACC scientific statement: a report of the American College of Cardiology. J Am Coll Cardiol. 2026;88(11):1255-1283. doi:10.1016/j.jacc.2026.05.033

11. Katsanos AH, Shoamanesh A, Palaiodimou L, Sharma M, Tsivgoulis G. Factor XIa inhibitors for secondary prevention after noncardioembolic stroke: a systematic review and meta-analysis. Neurology. 2026;107(7):e218521. doi:10.1212/WNL.0000000000218521