AstraZeneca Announces Subgroup Analyses from Phase IV TWILIGHT Trial of Brilinta Monotherapy Demonstrating Reduced Bleeding Risk Without Compromising Ischemic Protection in High-Risk Coronary Patients

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Recently, AstraZeneca announced the results of subgroup analyses from two arms (TWILIGHT-DM and TWILIGHT-COMPLEX) of the Phase IV independent study TWILIGHT on the anticoagulant Brilinta (ticagrelor). The data showed that in patients with high-risk coronary artery disease, 12 months of Brilinta monotherapy reduced the risk of clinically relevant bleeding compared to dual antiplatelet therapy (DAPT) with aspirin plus Brilinta, without increasing the risk of bleeding events.

TWILIGHT was a randomized, double-blind, placebo-controlled Phase IV study that enrolled 9,006 patients from 187 clinical centers across 11 countries. These patients exhibited high-risk clinical and/or anatomical features for ischemia or bleeding after undergoing percutaneous coronary intervention (PCI) with the implantation of at least one drug-eluting stent (DES); 64% of the patients had non-ST-elevation acute coronary syndrome (NSTE-ACS). In the study, all patients received Brilinta (90 mg twice daily) and enteric-coated aspirin (81–100 mg once daily) for 3 months following PCI. Among the 7,119 patients who adhered to dual antiplatelet therapy (DAPT) without experiencing major bleeding or ischemic events during the initial 3-month treatment period with Brilinta and aspirin, participants were randomized in a 1:1 ratio to either continue aspirin or switch to placebo for an additional 12 months, while both groups continued open-label Brilinta treatment.

The results showed that during the 12-month continuation of treatment, Brilinta monotherapy reduced the relative risk of BARC (Bleeding Academic Research Consortium) type 2, 3, and 5 bleeding events by 44%, with an absolute risk reduction of 3.1% (4.0% vs. 7.1%; HR=0.56; 95% CI: 0.45–0.68; p<0.001), compared to the Brilinta plus aspirin regimen. Furthermore, the composite risk of all-cause death, myocardial infarction, or stroke was similar between the two groups (3.9% vs. 3.9%; HR=0.99; 95% CI: 0.78–1.25; p<0.001 for non-inferiority).

In the two subgroups announced, all patients completed 3 months of dual antiplatelet therapy (DAPT) without major bleeding or ischemic events. These patients were randomly assigned to receive either placebo or aspirin while continuing open-label Brilinta treatment for 12 months. The TWILIGHT-DM subgroup included 2,620 diabetic patients who had undergone successful percutaneous coronary intervention (PCI), and the TWILIGHT-COMPLEX subgroup included 2,342 patients who had undergone successful complex PCI. PCI is a procedure to open blocked or narrowed coronary arteries. Complex PCI was defined as any of the following: treatment of three vessels, treatment of at least three lesions, total stent length >60 mm, implantation of two stents at a bifurcation, use of any atherectomy device, left main PCI, bypass graft surgery, or chronic total occlusion of the target lesion.

Subgroup analysis results showed that from 3 to 15 months after PCI (i.e., during the 12-month randomized treatment period), Brilinta monotherapy was associated with a lower rate of clinically relevant bleeding compared with DAPT, without an increased risk of ischemic events. In the TWILIGHT-DM and TWILIGHT-COMPLEX subgroups, the risk of clinically relevant bleeding was reduced by 35% and 46%, respectively, in patients receiving Brilinta monotherapy compared with those receiving DAPT, while the risk of ischemic events was similar.

The subgroup results were consistent with the overall trial results. Currently, in the clinical management of patients undergoing percutaneous coronary intervention (PCI), there is an unmet medical need for therapeutic strategies that reduce bleeding risk without compromising ischemic protection. These subgroup analyses provide critical insights supporting Brilinta as monotherapy in these high-risk patients.

Acute Coronary Syndrome (ACS) is a cardiovascular disease characterized by the rupture or erosion of atherosclerotic plaques in the coronary arteries, leading to secondary complete or incomplete occlusive thrombosis. This results in a severe reduction in myocardial blood supply (unstable angina) or complete obstruction (myocardial infarction).

Brilinta is an oral, reversible, direct-acting P2Y12 receptor antagonist that works by inhibiting platelet activation. To date, Brilinta has been approved in more than 110 countries for the treatment of ACS and in more than 70 countries for secondary prevention of cardiovascular events in high-risk patients who have experienced a myocardial infarction.

Brilinta in combination with aspirin has been proven to significantly reduce the risk of major adverse cardiovascular events (MACE) in patients with acute coronary syndrome (ACS) or a history of myocardial infarction (MI). The Brilinta and aspirin regimen is indicated for adult patients with ACS, or those with a history of MI who are at high risk for atherothrombotic events, for the prevention of atherothrombotic events.

Reference: Brilinta Reduced Bleeding vs. Dual Therapy in High-Risk Coronary Patients in Sub-Analyses from Phase IV TWILIGHT Trial

Original Title: AstraZeneca Announces Phase IV Clinical Subgroup Analysis Data for Brilinta: Monotherapy Reduces Bleeding Risk