Subgroup analysis of TWILIGHT trial patients with non-ST elevation acute coronary syndrome (NSTE-ACS) who underwent PCI showed Brilinta monotherapy reduced the risk of clinically relevant bleeding compared with dual antiplatelet therapy (DAPT)

Secondary endpoint of subgroup analysis showed similar rates of the composite of all-cause death, myocardial infarction or stroke between monotherapy and DAPT

Results of subgroup analysis of TWILIGHT randomised clinical trial presented at AHA Scientific Sessions 2019
 

New results from a pre-specified subgroup analysis of the TWILIGHT trial showed that Brilinta (ticagrelor) monotherapy reduced the risk of clinically relevant bleeding compared to dual antiplatelet therapy (DAPT) over 12 months in high-risk patients with non-ST elevation acute coronary syndromes (NSTE-ACS).  

The pre-specified subgroup analysis included 5,739 patients (64% of the overall TWILIGHT trial cohort of 9,006 patients) who had undergone successful percutaneous coronary intervention (PCI) with at least one drug eluting stent (DES) for NSTE-ACS. Following a three-month open-label treatment phase with ticagrelor (90mg BID) plus low-dose aspirin (81–100mg daily), 4,614 patients, who were free from major ischaemic or bleeding events, were randomised to either continue low-dose aspirin or matching placebo for an additional 12 months, with continuation of open-label ticagrelor.

Results of the NSTE-ACS subgroup analysis showed:

• Ticagrelor monotherapy was associated with a 53% relative reduction in the risk of the primary endpoint – Bleeding Academic Research Consortium (BARC) type 2, 3 or 5 bleeding – over one year, with an absolute risk reduction of 4.0%, compared to ticagrelor plus aspirin (3.6% vs. 7.6%, HR 0.47; 95% CI: 0.36-0.61).
• Also seen was a reduction in the risk of BARC 3 or 5 bleeding in patients treated with ticagrelor monotherapy versus ticagrelor plus aspirin over one year (0.8% vs. 2.1%).
• Thrombolysis in Myocardial Infarction (TIMI) major bleeding at one year was 0.5% for ticagrelor plus placebo and 1.0% for ticagrelor plus aspirin (nominal exploratory p=0.08).
• Rates of the key secondary endpoint – composite outcome of all-cause death, myocardial infarction (MI) or stroke – were similar between the two groups at one year (4.3% for ticagrelor plus placebo and 4.4% for ticagrelor plus aspirin [HR 0.97; 95% CI: 0.74-1.28]).
• Rates of other secondary endpoints also were similar between the two groups at one year – all-cause death (1.0% for ticagrelor plus placebo and 1.5% for ticagrelor plus aspirin), MI (3.1% and 3.1%), ischemic stroke (0.5% and 0.3%), and definite or probable stent thrombosis (0.4% and 0.6%).

Danilo Verge, Vice President Global Medical Affairs, Cardiovascular, Renal and Metabolism said: “The TWILIGHT trial provided important information about the longer-term management of high-risk patients who had undergone PCI. In this pre-specified subgroup analysis of patients with NSTE-ACS enrolled in TWILIGHT, treatment with ticagrelor monotherapy, without aspirin, after three months of DAPT was associated with a lower risk of bleeding compared with standard 12 months of dual antiplatelet therapy with ticagrelor plus aspirin.”

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 in New York, US, said: “The finding that ticagrelor monotherapy was not associated with an increased risk of all-cause death, MI or stroke compared to continuation of DAPT in NSTE-ACS patients enrolled in TWILIGHT, a finding which was also observed in the overall trial cohort, is important given that there was also a reduction in bleeding in this cohort.” 

Usman Baber, Chair of the TWILIGHT Clinical and Data Coordinating Center and Assistant Professor of Medicine and Cardiology at Icahn School of Medicine at Mount Sinai in New York, presented the findings during a late-breaking session at the AHA, said: “These findings challenge the conventional paradigm for maintenance of aspirin as a long-term component of dual antiplatelet therapy in high-risk patients with NSTE-ACS.”

Results of the TWILIGHT sub-analysis were presented in a late breaker oral presentation on 17 November 2019 at the American Heart Association (AHA) Scientific Sessions 2019 in Philadelphia, US.

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 75-150mg, unless specifically contraindicated.

About TWILIGHT

TWILIGHT was a randomised, double-blinded, placebo-controlled Phase IV trial. The study was designed and sponsored by the Icahn School of Medicine at Mount Sinai in New York, US. AstraZeneca provided study drug and funding through an investigator-initiated grant but had no influence on the study design or data analysis.

Patients were included in TWILIGHT if they had high-risk clinical and/or anatomical features for ischaemia or bleeding after undergoing PCI with insertion of at least one DES. STEMI presentation was an exclusion criterion; 64% (5,739) of the overall cohort had NSTE-ACS. In TWILIGHT, all enrolled patients (9,006) received ticagrelor (90mg twice daily) and enteric-coated aspirin (81-100mg daily) for three months after PCI. Patients who remained event-free and were adherent to DAPT during the three months of treatment with ticagrelor and aspirin (7,119) 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.

Results from the TWILIGHT full study population were presented in September 2019 at Transcatheter Cardiovascular Therapeutics (TCT) 2019, the annual scientific conference of the Cardiovascular Research Foundation, and published simultaneously in The New England Journal of Medicine.¹

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 CVRM

Cardiovascular, Renal & Metabolism (CVRM) together forms one of AstraZeneca’s three 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 comorbidities. The Company’s 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 cardiovascular 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 and Metabolism, and Respiratory. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca.

Contacts

References

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

2.     Baber U, et al. Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention for Acute Coronary Syndrome. In: American Heart Association’s Scientific Sessions 2019; 16-18 November, Philadelphia (PA): AHA 2019.