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 ischemic or bleeding events, were randomized 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 the BARC 3 or 5 bleeding for ticagrelor monotherapy versus ticagrelor plus aspirin at 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.
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.
BRILINTA is indicated to reduce the rate of cardiovascular death, myocardial infarction (MI), and stroke in patients with acute coronary syndrome (ACS) or a history of myocardial infarction. For at least the first 12 months following ACS, it is superior to clopidogrel. BRILINTA also reduces the rate of stent thrombosis in patients who have been stented for treatment of ACS.
BRILINTA is not indicated for use without aspirin or in patients undergoing PCI who have not had an ACS event.
In the management of ACS, initiate BRILINTA treatment with a 180-mg loading dose. Administer 90 mg twice daily during the first year after an ACS event. After one year administer 60 mg twice daily. Use BRILINTA with a daily maintenance dose of aspirin of 75-100 mg.