Ticagrelor alone vs. ticagrelor plus aspirin following percutaneous coronary intervention in patients with non-ST-segment elevation acute coronary syndromes: TWILIGHT-ACS

Abstract

Aims The aim of this study was to determine the effect of ticagrelor monotherapy on clinically relevant bleeding and major ischaemic events in relation to clinical presentation with and without non-ST elevation acute coronary syndromes (NSTE-ACS) among patients undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES). Methods and results We conducted a pre-specified subgroup analysis of The Ticagrelor With Aspirin or Alone in High Risk Patients After Coronary Intervention (TWILIGHT) trial, which enrolled 9006 patients with high-risk features undergoing PCI with DES. After 3 months of dual antiplatelet therapy (DAPT) with ticagrelor plus aspirin, 7119 adherent and event-free patients were randomized in a double-blind manner to ticagrelor plus placebo versus ticagrelor plus aspirin for 12 months. The primary outcome was Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding while the composite of all-cause death, myocardial infarction (MI), or stroke was the key secondary outcome. Among patients with NSTE-ACS (n = 4614), ticagrelor monotherapy reduced BARC 2, 3, or 5 bleeding by 53% [3.6% vs. 7.6%; hazard ratio (HR) 0.47; 95% confidence interval (CI) 0.36–0.61; P < 0.001) and in stable patients (n = 2503) by 24% (4.8% vs. 6.2%; HR 0.76; 95% CI 0.54–1.06; P = 0.11; nominal Pint = 0.03). Rates of all-cause death, MI, or stroke among those with (4.3% vs. 4.4%; HR 0.97; 95% CI 0.74–1.28; P = 0.84) and without (3.1% vs. 3.2%; HR 0.96; 95% CI 0.61–1.49; P = 0.85) NSTE-ACS were similar between treatment arms irrespective of clinical presentation (Pint = 0.96). Conclusion Among patients with or without NSTE-ACS who have completed an initial 3-month course of DAPT following PCI with DES, ticagrelor monotherapy reduced clinically meaningful bleeding events without increasing ischaemic risk as compared with ticagrelor plus aspirin. The benefits of ticagrelor monotherapy with respect to bleeding events were more pronounced in patients with NSTE-ACS. Trial registration Clinicaltrials.gov identifier: NCT02270242.

Acute and one-year clinical outcomes of pre-stenting intravascular ultrasound: a patient-level meta-analysis of randomised clinical trials

“…Two trials explored the effect of ticagrelor monotherapy on bleeding and ischaemic events in ACS patients undergoing PCI. TWILIGHTACS confirmed that dropping aspirin after 3 months of dual antiplatelet therapy (DAPT) with ticagrelor reduced bleeding risk by 53% without increasing the rate of ischaemic events [95]. Along the same line, the TICO randomized trial showed that switching to ticagrelor monotherapy after 3months of DAPT reduced major bleeding without increasing ischaemic risk compared with 12 months of DAPT in ACS patients [96].…”

Efficacy and Safety of Dual Antiplatelet Therapy in Patients Undergoing Coronary Stent Implantation: A Systematic Review and Network Meta-Analysis

“…Subgroup analysis focusing on the ACS population favored DAPT 3Mo + P2Y12, despite 2020 ESC guidelines recommending 12-month DAPT. This conclusion incorporated the data from the TICO trial and post hoc ACS sub-analysis of the TWILIGHT trial [ 5 , 43 ]. The TICO trial confirmed that ticagrelor monotherapy following 3-month DAPT, when compared with 12-month ticagrelor-based DAPT, resulted in a modest but statistically significant reduction in a composite outcome of major bleeding and cardiovascular events [ 5 ].…”

“…Results of the participants with ACS and the published sub-analyses are summarized in Supplementary Table S11 [5,17,19,20,26,[38][39][40][41][42][43]. Eleven trials with a total of 29863 participants enrolled.…”

“…is conclusion incorporated the data from the TICO trial and post hoc ACS subanalysis of the TWILIGHT trial [5,43].…”

Ticagrelor: clinical development and future potential

“…In a pre-specified subgroup analysis, TWILIGHT-ACS highlighted that ticagrelor monotherapy provided greater magnitude of reduced bleeding in 4614 patients with NSTE-ACS (3.6% [monotherapy] vs. 7.6% [DAPT]; HR, 0.47; 95% CI 0.36-0.61; P < 0.001) than those with CCS (4.8% vs. 6.2%; HR, 0.76; 95% CI 0.54-1.06; P = 0.11; nominal P interaction = 0.03), while the risk of MACE was similar for both treatment groups and independent of the clinical presentation [132]. In support of these findings, but in a low-risk population, the Ticagrelor Monotherapy After three Months in the Patients Treated With New Generation Sirolimus-eluting Stent for ACS (TICO) study demonstrated that switching to ticagrelor monotherapy after three months of DAPT significantly reduced the frequency of the composite primary endpoint Considering the evidence, it is becoming increasingly apparent that a tailored approach is required for ticagrelortreated patients, particularly those with ACS.…”