American College of Cardiology

American College of Cardiology

Source:

Patel MR, et al. Featured Clinical Research II. Presented at: American College of Cardiology Scientific Session; April 2-4, 2022; Washington, D.C. (hybrid meeting).

Disclosures: The study was funded by Bayer. Patel reports receiving research grants from Bayer, HeartFlow, Idorsia, Janssen, the NHLBI and Novartis and consulting and/or serving on an advisory board for Bayer, HeartFlow, Janssen and Medscape. Please see the study for all other authors’ relevant financial disclosures.
April 28, 2022
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Asundexian confers lower bleeding rates vs. apixaban for stroke prevention in AF

Source:

Patel MR, et al. Featured Clinical Research II. Presented at: American College of Cardiology Scientific Session; April 2-4, 2022; Washington, D.C. (hybrid meeting).

Disclosures: The study was funded by Bayer. Patel reports receiving research grants from Bayer, HeartFlow, Idorsia, Janssen, the NHLBI and Novartis and consulting and/or serving on an advisory board for Bayer, HeartFlow, Janssen and Medscape. Please see the study for all other authors’ relevant financial disclosures.
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WASHINGTON — In patients with atrial fibrillation requiring stroke prevention, the novel factor XIa inhibitor asundexian was associated with lower bleeding rates compared with apixaban, according to the results of the PACIFIC-AF trial.

Results of the randomized, double-blind, phase 2 PACIFIC-AF trial were presented at the American College of Cardiology Scientific Session and simultaneously published in The Lancet.

Atrial fibrillation smartphone
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The researchers randomly assigned 755 patients (mean age, 74 years; 41% women; 29% with chronic kidney disease) with AF, a CHA2DS2-VASc score of at least 2 if male or 3 if female (mean, 3.9) and elevated bleeding risk to asundexian (Bayer) 20 mg daily, asundexian 50 mg daily or apixaban (Eliquis, Bristol Myers Squibb/Pfizer).

Manesh R. Patel

Manesh R. Patel, MD, FACC, FAHA, FSCAI, chief of the divisions of cardiology and clinical pharmacology and Richard Sean Stack, MD Distinguished Professor at Duke University School of Medicine and member in the Duke Clinical Research Institute, said during a presentation that factor Xa inhibitors such as apixaban prevent pathological thrombi but can also prevent the benefits of blood clots, whereas “the hypothesis biologically for factor XI inhibition is to hopefully uncouple this hemostasis from thrombosis in such a way that, when factor XI inhibition happens through that contact pathway, no pathological thrombosis can occur, or at least some of it can be prevented, while potentially preserving some of the tissue factor pathway thrombin generation that would lead to the beneficial blood clots that form.”

Asundexian 20 mg inhibited factor XIa activity by 81% at trough concentrations and 90% at peak concentrations, whereas asundexian 50 mg inhibited factor XIa activity by 92% at trough concentrations and 94% at peak concentrations, Patel said during the presentation.

The primary endpoint of major or clinically relevant nonmajor bleeding by International Society on Thrombosis and Haemostasis criteria occurred in three patients from the asundexian 20 mg group, one patient from the asundexian 50 mg group and six patients from the apixaban group, and there were no major bleeding events in any group, according to the researchers.

Compared with the apixaban group, the ratio of incidence proportion was 0.5 for the asundexian 20 mg group (90% CI, 0.14-1.68), 0.16 for the asundexian 50 mg group (90% CI, 0.01-0.99) and 0.33 (90% CI, 0.09-0.97) for the pooled asundexian group, Patel and colleagues found.

Rates of any adverse event were 47% in both asundexian groups and 49% in the apixaban group, according to the researchers.

“Asundexian, a small oral factor XIa inhibitor, was well tolerated in this phase 2 study of more than 750 patients with atrial fibrillation,” Patel said during the presentation. “It had significantly lower bleeding rates for patients randomized to either dose compared to apixaban. The factor XI inhibition data represent a promising strategy to prevent pathologic thrombi while potentially minimizing bleeding risk in our AF patients. Of course, a phase 3 trial will be required.”

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