19 November 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 over 12 months in high-risk patients with non-ST elevation acute coronary syndromes (NSTE-ACS), British-Swedish pharmaceutical company AstraZeneca (OTC: AZNCF) said.
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 with at least one drug eluting stent 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 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 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 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%).
Results of the TWILIGHT sub-analysis were presented in a late breaker oral presentation on 17 November 2019 at the American Heart Association Scientific Sessions 2019 in Philadelphia, US.
Brilinta is indicated to reduce the rate of cardiovascular death, myocardial infarction, and stroke in patients with acute coronary syndrome 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.
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 ischemia 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 randomized 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 2019, the annual scientific conference of the Cardiovascular Research Foundation, and published simultaneously in The New England Journal of Medicine.
Brilinta is an oral, reversibly binding, 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 events (myocardial infarction, stroke or CV death) in patients with acute coronary syndrome or a history of MI.