Asundexian for secondary prevention after acute MI scores high in early trial

The oral activated factor XI (FXIa) inhibitor asundexian, when taken with aspirin plus a P2Y12 inhibitor, appears to facilitate dose-dependent, near-complete inhibition of FXIa activity with a low rate of ischaemic events and without a significant increase in bleeding, according to the results of a phase II trial.

The double-blind, placebo-controlled, dose-ranging trial randomized 1,601 patients (median age 68 years, 23 percent female, 51 percent with ST-segment–elevation myocardial infarction [MI]) with recent acute MI to receive oral asundexian at 10, 20, or 50 mg or placebo once daily for 6–12 months. Randomization was performed within 5 days of the index MI. In addition, the patients received dual antiplatelet therapy with aspirin plus a P2Y12 inhibitor.

The effect of asundexian on FXIa inhibition was assessed at 4 weeks. The prespecified efficacy outcome was a composite of cardiovascular death, MI, stroke, or stent thrombosis, while the prespecified main safety outcome was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding.

Of the patients, 80 percent received aspirin plus ticagrelor or prasugrel and 99 percent underwent percutaneous coronary intervention before randomization. Asundexian resulted in dose-related inhibition of FXIa activity, with 50 mg resulting in >90 percent inhibition.

Over a median follow-up of 368 days, bleeding occurred in 30 (7.6 percent) patients on asundexian 10 mg, 32 (8.1 percent) on 20 mg, 42 (10.5 percent) on 50 mg, and 36 (9.0 percent) on placebo (pooled asundexian vs placebo: hazard ratio [HR], 0.98, 90 percent confidence interval [CI], 0.71–1.35).

The composite outcome was documented in 27 (6.8 percent) patients on asundexian 10 mg, 24 (6.0 percent) on 20 mg, 22 (5.5 percent) on 50 mg, and 22 (5.5 percent) on placebo (pooled asundexian 20 and 50 mg vs placebo: HR, 1.05, 90 percent CI, 0.69–1.61).

The findings support the evaluation of asundexian at a dose of 50 mg daily in an adequately powered clinical trial of patients who experienced acute MI.