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

AstraZenecaNew data from TWILIGHT, a Phase IV independent trial (funded by AstraZeneca), showed that in patients at high-bleeding risk who underwent PCI and completed 3 months of dual antiplatelet therapy, Brilinta (ticagrelor) monotherapy (90mg twice daily) reduced the risk of BARC (Bleeding Academic Research Consortium) type 2, 3 or 5 bleeding compared to Brilinta plus low-dose aspirin after 12 months. (1)

In the trial, 9,006 patients received open-label ticagrelor (90mg twice daily) and aspirin (81-100mg daily) for three months after a PCI. The 7,119 patients that remained event-free of major bleeding or an ischaemic event during the three months of treatment with ticagrelor and aspirin were randomised to either double-blinded aspirin or placebo for an additional 12 months, with continuation of open-label ticagrelor.(1)

Ticagrelor monotherapy was associated with a 44% lower risk of BARC 2, 3 or 5 bleeding over one year, with an absolute risk reduction of 3.1%, compared to ticagrelor plus aspirin.(1)

The incidence of the primary endpoint, time to first occurrence of BARC type 2, 3 or 5 bleeding between month 3 and 15, was 4.0% in patients treated with ticagrelor plus placebo compared to 7.1% in patients treated with ticagrelor plus aspirin (HR 0.56; 95% CI 0.45 to 0.68; p<0.001).(1)

The incidence of BARC 3 or 5 bleeding was also lower (1.0% vs 2.0%, HR, 0.49; 95% CI, 0.33 to 0.74) with ticagrelor plus placebo versus ticagrelor plus aspirin. Rates of the composite of all-cause death, myocardial infarction or stroke, a key secondary endpoint, were similar between the two groups 3.9% and 3.9%, respectively for ticagrelor plus placebo and ticagrelor plus aspirin (HR 0.99; 95% CI 0.78 to 1.25; non-inferiority p<0.001).(1)

Roxana Mehran, TWILIGHT's Global Principal Investigator and Director of the Center for Interventional Cardiovascular Research and Clinical Trials at Mount Sinai Heart and Professor of Cardiology, and Population Health Science and Policy, at Icahn School of Medicine at Mount Sinai, said "In high-risk PCI patients further ischemic events remain a life-threatening concern. As seen in TWILIGHT, in patients who tolerated three months of dual antiplatelet therapy, lowering the risk of major bleeding while preserving the ischemic benefit using ticagrelor monotherapy is an important clinical advance for these patients."

Danilo Verge, Vice President Global Medical Affairs, Cardiovascular, Renal and Metabolism said: "The benefit of Brilinta (ticagrelor) in reducing thrombosis following the placement of a stent is well established and recommended in guidelines in patients with acute coronary syndromes. The results from the TWILIGHT trial show that following percutaneous coronary intervention in high-risk patients, the withdrawal of aspirin while continuing ticagrelor monotherapy resulted in a lower bleeding rate, while showing non-inferiority for the risk of composite of death, MI, or stroke versus dual antiplatelet therapy."

Results from TWILIGHT were presented on Thursday 26 September 2019 at Transcatheter Cardiovascular Therapeutics (TCT) 2019, the annual scientific conference of the Cardiovascular Research Foundation, in San Francisco, US and published simultaneously in the New England Journal of Medicine.

Ticagrelor co-administered with aspirin, is indicated for the prevention of atherothrombotic events in adult patients with: acute coronary syndromes (ACS); or a history of myocardial infarction (MI) and a high risk of developing an atherothrombotic event. Patients taking ticagrelor should also take a daily low maintenance dose of aspirin 75-150 mg, unless specifically contraindicated.

About TWILIGHT

The TWILIGHT study was designed and sponsored by the Icahn School of Medicine at Mount Sinai. AstraZeneca provided study drug and funding through an investigator-initiated grant.

Patients were included if they had high-risk clinical and/or anatomical features for ischaemia or bleeding after undergoing PCI with insertion of at least one drug-eluting stent (DES). STEMI presentation was an exclusion criteria; 65% of the overall cohort had NSTE-ACS. All enrolled patients (9006) received ticagrelor (90mg twice daily) and enteric-coated aspirin (81-100mg daily) for three months after PCI. Patients that remained event-free during the three months of treatment with ticagrelor and aspirin (7119) were randomised 1:1 in a double-blind manner to either continue aspirin or switch to matched placebo for an additional 12 months, with continuation of open-label ticagrelor in both groups. The trial included 187 sites from across 11 countries, with the majority of patients recruited from the US.

About Brilinta

Brilinta is an oral, reversible, direct-acting P2Y12 receptor antagonist that works by inhibiting platelet activation. Brilinta, together with aspirin, has been shown to significantly reduce the risk of major adverse cardiovascular (CV) events (myocardial infarction, stroke or CV death), in patients with acute coronary syndrome (ACS) or a history of myocardial infarction (MI).

Brilinta, co-administered with aspirin, is indicated for the prevention of atherothrombotic events in adult patients with ACS, or for patients with a history of MI and a high risk of developing an atherothrombotic event.

About AstraZeneca in CV, Renal & Metabolism (CVRM)

CV, renal and metabolism together form one of AstraZeneca’s main therapy areas and is a key growth driver for the Company. By following the science to understand more clearly the underlying links between the heart, kidneys and pancreas, AstraZeneca is investing in a portfolio of medicines to protect organs and improve outcomes by slowing disease progression, reducing risks and tackling co-morbidities. Our ambition is to modify or halt the natural course of CVRM diseases and potentially regenerate organs and restore function, by continuing to deliver transformative science that improves treatment practices and CV health for millions of patients worldwide.

About AstraZeneca

AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal & Metabolism (CVRM) and Respiratory. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide.

1. Mehran R, et al. Ticagrelor With or Without Aspirin in High-Risk Patients After PCI. New England Journal of Medicine. DOI: 10.1056/NEJMoa1908419

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