OCEANIC-AF: Asundexian inferior to apixaban for ischaemic stroke prevention in AF

The factor XIa inhibitor asundexian was inferior to apixaban in preventing stroke or systemic thromboembolism in patients with atrial fibrillation (AF) and an increased risk for stroke in the large, phase 3 OCEANIC-AF trial.

“Although direct oral anticoagulants [DOACs] are accepted as first-line therapy for patients with AF, patients treated with DOACs still face a bleeding risk of 2.7–3.5% per year,” explained Dr Manesh Patel (Duke Clinical Research Institute, NC, USA) [1]. Undertreatment, underdosing, and poor treatment compliance are other challenges linked to treatment with DOACs. The phase 3 OCEANIC-AF trial (NCT05643573) compared the factor XIa inhibitor asundexian (50 mg, once daily) to the established DOAC apixaban, a factor Xa inhibitor, in a large population of patients with AF at risk for stroke or systemic embolism (n=14,830) [2]. Although the planned sample size was 18,000, the trial was terminated early due to the inferiority of the investigational agent in the primary efficacy endpoint of stroke/systemic embolism.

After a median follow-up of 155 days, the rate of stroke/systemic embolism was 1.3% in the asundexian arm versus 0.4% in the apixaban arm (HR 3.79; 95% CI 2.46–5.83) [1]. Asundexian was associated with fewer ISTH major bleeding events than apixaban (0.2% vs 0.7%; HR 0.32; 95% CI 0.18–0.55).

The OCEANIC-AF study revealed that asundexian was inferior to apixaban for the prevention of stroke and systemic embolism in a population of patients with AF and a high risk for stroke. Dr Patel argued that more research is needed to determine the optimal degree of factor XIa inhibition for stroke prevention in patients with AF. “It may be that (near) total suppression of factor XIa is needed to achieve the efficacy endpoints,” he reasoned, suggesting that the dose may have been insufficient. Multiple factor XIa inhibition trials in various indications are ongoing, further informing the community about the effect of factor XIa inhibition.

1. 
   
   1. Patel MR, et al. OCEANIC-AF: asundexian vs apixaban in patients with atrial fibrillation. HOTLINE 6, ESC Congress 2024, 30 Aug–02 Sept, London, UK.
   2. Piccini JP, et al. N Engl J Med 2024; Sept 1. DOI: 10.1056/NEJMoa2407105.

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Posted on 7 November 20247 November 2024