AstraZeneca Highlights Superior Bleeding Risk Reduction with Brilinta Monotherapy in High-Risk PCI Patients Based on TWILIGHT Trial

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Recently, at the 2019 Scientific Sessions of the Transcatheter Cardiovascular Therapeutics (TCT) conference hosted by the Cardiovascular Research Foundation in the United States, AstraZeneca announced new data from TWILIGHT, an independent Phase IV study of the anticoagulant Brilinta (ticagrelor). The results showed that among high-risk patients who had undergone percutaneous coronary intervention (PCI) and completed three months of dual antiplatelet therapy, continuing treatment for 12 months with Brilinta monotherapy reduced the risk of clinically relevant bleeding compared with Brilinta plus low-dose aspirin, without increasing the composite risk of major adverse cardiovascular events. The findings were simultaneously published in the New England Journal of Medicine (NEJM).

The TWILIGHT study enrolled a total of 9,006 patients from 187 treatment centers across 11 countries. These patients presented 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, and 65% of them had non-ST-segment elevation acute coronary syndrome. 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 these patients, 7,119 who did not experience major bleeding or ischemic events within the first 3 months of treatment with Brilinta and aspirin were randomized in a 1:1 ratio to continue either aspirin or switch to placebo for an additional 12 months, while continuing open-label Brilinta therapy.

The results showed that during the continued 12-month treatment period (i.e., from month 3 to month 15), Brilinta monotherapy reduced the risk of BARC (Bleeding Academic Research Consortium) type 2, 3, and 5 bleeding events by 44% compared with the Brilinta plus aspirin regimen, with an absolute risk reduction of 3.1%. For the primary endpoint, namely the incidence of the first BARC type 2, 3, or 5 bleeding event, the rates were 4.0% in the Brilinta plus placebo group and 7.1% in the Brilinta plus aspirin group (HR=0.56, 95% CI: 0.45–0.68, p<0.001).

Compared with the Brilinta plus aspirin treatment group, the Brilinta plus placebo group also had a lower incidence of BARC type 3 or 5 bleeding events (1.0% vs. 2.0%; HR=0.49; 95% CI: 0.33–0.74). The composite rates of all-cause death, myocardial infarction, or stroke (key secondary endpoints) were similar between the two groups (3.9% vs. 3.9%; HR=0.99; 95% CI: 0.78–1.25; p<0.001).

The benefits of Brilinta in reducing thrombosis after stent implantation have been well established and are recommended in the treatment guidelines for patients with acute coronary syndrome (ACS). In high-risk PCI patients, further ischemic events remain a life-threatening concern. The results of the TWILIGHT study showed that in high-risk patients who tolerated 3 months of dual antiplatelet therapy, discontinuing aspirin but continuing monotherapy with Brilinta reduced the risk of major bleeding while maintaining ischemic benefit, demonstrating non-inferiority in the composite risk of death, myocardial infarction, or stroke compared to continuing dual antiplatelet therapy.

Brilinta is an oral, reversible, direct-acting P2Y12 receptor antagonist that works by inhibiting platelet activation. In patients with acute coronary syndrome (ACS) or a history of myocardial infarction, Brilinta combined with aspirin has been shown to significantly reduce the risk of major adverse cardiovascular events. The Brilinta and aspirin regimen is indicated for adult patients with ACS, or those with a history of myocardial infarction who are at high risk of developing atherothrombotic events, to prevent atherothrombotic events. Brilinta can also reduce the rate of stent thrombosis in ACS patients undergoing stent therapy.

Earlier this month, AstraZeneca announced detailed data from the THEMIS Phase III clinical study evaluating cardiovascular outcomes with Brilinta. The results showed that in patients with both coronary artery disease and type 2 diabetes, Brilinta combined with aspirin significantly reduced the relative risk of major adverse cardiovascular events (MACE) by 10% compared with aspirin alone. Furthermore, a subgroup analysis of patients who had previously undergone percutaneous coronary intervention (PCI), accounting for approximately 58% of the total study population, demonstrated that Brilinta combined with aspirin provided more favorable clinical benefits, reducing the relative risk of MACE by 15% compared with aspirin alone.

In 2018, Brilinta achieved sales of $1.321 billion, representing a 22% increase from 2017, making it one of AstraZeneca’s best-selling drugs. The success of the THEMIS cardiovascular outcomes study is expected to further enhance Brilinta’s commercial potential.

Reference Sources:

1、BRILINTA Monotherapy in High-Bleeding Risk Patients Who Underwent PCI had Reduced Risk of Clinically Relevant Bleeding Than With Dual Antiplatelet Therapy in the TWILIGHT Trial

2、Ticagrelor with or without Aspirin in High-Risk Patients after PCI