Asundexian did not prevent stroke, systemic embolism vs. apixaban in atrial fibrillation
Click Here to Manage Email Alerts
Key takeaways:
- Asundexian did not prevent stroke or systemic embolism vs. apixaban in patients with atrial fibrillation despite less bleeding.
- A larger dose may be needed for complete factor XI inhibition.
Treatment of atrial fibrillation with asundexian, a novel factor XIa inhibitor, was associated with increased stroke and systemic embolism risk despite lower bleeding risk compared with apixaban, a speaker reported.
The full results of the phase 3 OCEANIC-AF trial of asundexian (Bayer) for the prevention of stroke and systemic embolism in patients with AF were presented at the European Society of Cardiology Congress and simultaneously published in The New England Journal of Medicine.
As Healio previously reported, Bayer announced in November of 2023 that the OCEANIC-AF trial was halted due to failure of efficacy of asundexian compared with the direct oral anticoagulant (DOAC) apixaban (Eliquis, Bristol Myers Squibb/Pfizer).
“Despite good medical therapy in some countries, worldwide is still limited in patients with atrial fibrillation in three ways. No. 1, there are patients who do not get treated, as much as 30% in some areas. No. 2 is undertreatment. No. 3 is people who cannot tolerate the therapy and stop. Those all happen likely due to bleeding or fear of bleeding,” Manesh R. Patel, MD, cardiologist and interventional cardiologist at Duke Health and member of the Duke Clinical Research Institute, said during a press conference. “It’s on that background that OCEANIC-AF was conducted.”
OCEANIC-AF was a randomized trial in which 14,810 patients with AF were assigned to either once-daily asundexian 50 mg or apixaban 5 mg or 2.5 mg twice daily (mean age, 74 years; 35% women; 70% white). The overall average CHA2DS2-VASc score in each group was 4.3.
The primary efficacy endpoint was stroke or systemic embolism. The primary safety endpoint was International Society on Thrombosis and Hemostasis (ISTH) major bleeding. The primary net clinical benefit endpoint was a combination of both efficacy and safety endpoints.
Over 24 months of follow-up, risk for stroke, systemic embolism or ischemic stroke was approximately fourfold higher among patients with AF assigned to asundexian compared with apixaban:
- stroke or systemic embolism (cause-specific HR = 3.79; 95% CI, 2.46-5.83);
- ischemic stroke or systemic embolism (csHR = 4.38; 95% CI, 2.76-6.96); and
- ischemic stroke (csHR = 4.06; 95% CI, 2.52-6.54).
Despite lower incidence and risk for ISTH major bleeding in the asundexian group (csHR = 0.32; 95% CI, 0.18-0.55), risk for the net clinical benefit endpoint, a composite of stroke, systemic embolism and ISTH major bleeding, was higher compared with apixaban (csHR = 1.61; 95% CI, 1.21-2.15).
“Asundexian 50 mg once daily was inferior for the prevention of stroke and systemic embolism compared with apixaban in patients with atrial fibrillation at high risk for stroke,” Patel said during the press conference. “The majority of these patients had previously been treated with an oral anticoagulant and the rate of stroke and systemic embolism in patients with apixaban who are treated for some time was lower than has previously been observed.”
Patel and colleagues subsequently conducted a prespecified post hoc analysis of OCEANIC-AF to assess the impact of asundexian and apixaban based on anticoagulation status at baseline.
The main results of the trial were consistent among patients with AF who had previously taken an oral anticoagulant, with a more than fourfold increase in risk for stroke or systemic embolism associated with asundexian (HR = 4.66; 95% CI, 2.84-7.65). However, while still elevated compared with apixaban, risk for stroke was lower among patients assigned to asundexian who were anticoagulant naive at baseline (HR = 1.42; 95% CI, 0.54-3.73).
“Clearly, more research is needed to determine the correct or needed amount of factor XI inhibition for atrial fibrillation in stroke prevention. We’re doing ongoing analyses, but it may be that you need total suppression of factor XIa activity for this indication against a DOAC,” Patel said during the press conference. “Importantly, that may speak to the dose of the drug used in this study and may speak to how much activity inhibition is needed.
“Prior use of oral anticoagulants without clinical issues and current medical therapies have led to lower rates of stroke, systemic embolism and bleeding compared with historical data on patient risk,” he said. “The apixaban arm in this trial did quite well, but obviously those patients came into the trial having been on oral anticoagulants and may highlight patients that respond to those therapies without having issues.”
Reference:
Collapse
Patel M, et al. Hot line 6. Presented at: European Society of Cardiology Congress; Aug. 30-Sept. 2, 2024; London (hybrid meeting).
Read more about
Click Here to Manage Email Alerts