Evaluating the safety and effectiveness of different doses of asundexian in patients with acute myocardial infarction treated with dual antiplatelet therapy.

This study investigated the safety and effectiveness of different doses of asundexian (BAY 2433334) in patients with acute myocardial infarction (MI; heart attack) treated with dual antiplatelet therapy (DAPT). The data showed that asundexian 50 mg when added to DAPT inhibits blood clotting factor XIa by more than 90% without significantly increasing the risk of bleeding in these patients.

After an acute MI (heart attack), patients are at risk for recurrent ischaemic events, including cardiovascular death, heart attacks, stroke, and stent thrombosis (blockage of stent due to blood clots). Dual antiplatelet therapy (DAPT) with acetylsalicylic acid (Aspirin) and ticagrelor (Brilique) are effective at reducing these events but increases the risk of bleeding.

Factor XI is a protein in the blood which is transformed into its active protein form (Factor XIa) during blood coagulation. Asundexian is a new oral anticoagulant that inhibits factor XIa. Factor XIa inhibitors have the potential to reduce the risk of bleeding and ischaemic events. However, the safety and effectiveness of different doses asundexian in patients with acute MI treated with DAPT are still unknown.

This study involved 1601 patients with acute MI. Patients were randomly assigned into four groups. Group 1 included 397 patients who received 10 mg of asundexian daily. Group 2 included 401 patients who received 20 mg of asundexian daily. Group 3 included 402 patients who received 50 mg of asundexian daily. Group 4 included 401 patients who received a matching placebo. All patients received DAPT with aspirin plus a P2Y12 inhibitor such as ticagrelor, prasugrel (Effient) or clopidogrel (Plavix). The average follow-up time was 368 days.

After 6 months, bleeding events occurred in 7.6% in group 1, 8.1% in group 2, and 10.5% in group 3 compared to 9% in group 4. These differences were not statistically significant.

Heart attacks, stroke, death, and stent thrombosis (blockage of stent) occurred in 6.8% in group 1, 6% in group 2, and 5.5% in group 3 compared to 5.5% in group 4. These differences were not statistically significant.

Asundexian effectively inhibited factor XIa activity, by more than 70% with the 10 mg dose, 80% with the 20 mg dose, and 90% with the 50 mg dose.

This study concluded that asundexian 50 mg when added to DAPT inhibits factor XIa by more than 90% without significantly increasing the risk of bleeding in patients with acute MI.

This study was funded by Bayer, the manufacturer of asundexian.