Asundexian Versus Apixaban in Patients With Atrial Fibrillation - OCEANIC-AF

Sep 01, 2024
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Author/Summarized by Author:
Amit Saha, MD
Summary Reviewer:
Dharam J. Kumbhani, MD, SM, FACC
Trial Sponsor:
Bayer
Date Presented:
09/01/2024
Date Published:
09/01/2024
Original Posted Date:
09/01/2024
References

Contribution To Literature:

The OCEANIC-AF trial showed that in patients with AF who warrant oral anticoagulant therapy, the selective factor XIa inhibitor asundexian was associated with fewer major bleeding events but an increased risk of stroke or systemic thromboembolism compared with apixaban.

Description:

The goal of the trial was to determine whether asundexian, a direct and selective factor XIa inhibitor, is 1) noninferior in preventing stroke or systemic thromboembolism, and 2) superior with respect to major bleeding risk compared with apixaban in patients with atrial fibrillation (AF) requiring oral anticoagulant therapy.

Study Design

  • International
  • Double-blind, double-dummy
  • Active comparator-controlled

Patients with AF and at increased thrombotic risk were randomized in a 1:1 fashion to receive asundexian 50 mg once daily or standard (5 mg) or reduced dose (2.5 mg) apixaban according to current guidelines. Each arm also received a matching placebo of their nonassigned treatment drug to maintain blinding despite the twice daily dosing of apixaban.

  • Total number of enrollees: 14,810
  • Median follow-up: 155 days
  • Mean patient age: 74 years
  • Percentage female: 35%

Inclusion criteria:

  • Age ≥18 years
  • Electrocardiographic evidence of AF within the past 12 months
  • CHA2DS2-VASc ≥3 (men) or ≥4 (women), or ≥2 (men) or ≥3 (women) with ≥1 enrichment criterion:
  • Age ≥70 years
  • Prior stroke, transient ischemic attack (TIA), or systemic embolism (SE)
  • Estimated glomerular filtration rate (eGFR) <50 mL/min/1.73 m2
  • Prior nontraumatic major bleeding
  • Concurrent antiplatelet therapy
  • ≤6 weeks of oral anticoagulant before randomization

Exclusion criteria:

  • Mechanical heart valve prosthesis
  • Valvular AF
  • Ischemic stroke ≤7 days prior
  • eGFR <25 mL/min/1.73 m2

Other salient features/characteristics:

  • Mean CHA2DS2-VASc score: 4.3
  • Prior stroke/TIA: 18%
  • Paroxysmal AF: 37%

Principal Findings:

The trial was terminated prematurely at the recommendation of the independent data safety monitoring committee due to a higher incidence of stroke or SE in the asundexian treatment group.

Primary efficacy outcome, stroke or SE, for asundexian vs. apixaban: 1.3% vs. 0.4% (hazard ratio [HR] 3.79, 95% confidence interval [CI] 2.46-5.83)

Primary safety outcome, International Society on Thrombosis and Haemostasis (ISTH) major bleeding, for asundexian vs. apixaban: 0.2% vs. 0.7% (HR 0.32, 95% CI 0.18-0.55)

Secondary outcomes for asundexian vs. apixaban:

  • All-cause mortality: 0.8% vs. 1.0% (HR 0.84, 95% CI 0.60-1.19)
  • Composite of stroke, SE, or ISTH major bleeding, for asundexian vs. apixaban:  1.6% vs. 1.0% (HR 1.61, 95% CI 1.21-2.15)
  • ISTH major or clinically relevant nonmajor bleeding: 1.1% vs. 2.6% (HR 0.44, 95% CI 0.34-0.57)

Interpretation:

In this phase 3 trial in patients with AF, the factor XIa inhibitor asundexian resulted in an increased risk of stroke or systemic thromboembolism compared with apixaban; the risk of major bleeding was lower. This treatment risk difference for stroke/SE became readily apparent between the two arms before 30 days, prompting early termination of the trial after a median follow-up period of <6 months.

It is unclear whether the current findings reflect inadequate pharmacodynamic activity at the studied dose or, more broadly, if factor XIa inhibition is a reasonable alternative to current oral anticoagulant options in AF. Given the reduced incidence of both cardioembolic and nontraumatic bleeding events observed in individuals with factor XI deficiency, further investigation into novel therapies acting on this pathway remains warranted.

References:

Piccini JP, Patel MR, Steffel J, et al., for the OCEANIC-AF Steering Committee and Investigators. Asundexian Versus Apixaban in Patients With Atrial Fibrillation. N Engl J Med 2024;Sep 1:[Epub ahead of print].

Presented by Dr. Manesh Patel at the European Society of Cardiology Congress, London, UK, September 1, 2024.

Clinical Topics: Anticoagulation Management, Arrhythmias and Clinical EP, Anticoagulation Management and Atrial Fibrillation, Atrial Fibrillation/Supraventricular Arrhythmias

Keywords: Atrial Fibrillation, Anticoagulants, Hemorrhage, Stroke, Thromboembolism, ESC Congress, ESC24


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