Long-term ticagrelor monotherapy versus standard dual antiplatelet therapy followed by aspirin monotherapy in patients undergoing biolimus-eluting stent implantation: rationale and design of the GLOBAL LEADERS trial

Abstract

Aims: The GLOBAL LEADERS trial is a superiority study in patients undergoing percutaneous coronary intervention, with a uniform use of Biolimus A9-eluting stents (BES) and bivalirudin. GLOBAL LEADERS was designed to assess whether a 24-month antithrombotic regimen with ticagrelor and one month of acetylsalicylic acid (ASA), compared to conventional dual antiplatelet therapy (DAPT), improves outcomes.Methods and results: Patients (n >16,000) are randomised (1:1 ratio) to ticagrelor 90 mg twice daily for 24 months plus ASA ≤100 mg for one month versus DAPT with either ticagrelor (acute coronary syndrome) or clopidogrel (stable coronary artery disease) for 12 months plus ASA ≤100 mg for 24 months. The primary outcome is a composite of all-cause mortality or non-fatal, new Q-wave myocardial infarction at 24 months. The key safety endpoint is investigator-reported class 3 or 5 bleeding according to the Bleeding Academic Research Consortium (BARC) definitions. Sensitivity analysis will be carried out to explore potential differences in outcome across geographic regions and according to specific angiographic and clinical risk estimates. Conclusions:The GLOBAL LEADERS trial aims to assess the role of ticagrelor as a single antiplatelet agent after a short course of DAPT for the long-term prevention of cardiac adverse events, across a wide spectrum of patients, following BES implantation. KEYWORDS

2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS

“…Until recently, there were only limited data addressing this issue from beyond the periprocedural phase to 1 year. By now, two studies addressing such a step-down concept have finished recruitment: Testing Responsiveness to Platelet Inhibition on Chronic Antiplatelet Treatment For Acute Coronary Syndromes Trial (TROPICAL-ACS) (NCT01959451) with a stepdown from prasugrel to clopidogrel after the peri-interventional phase in acute MI; and GLOBAL-LEADERS (NCT01813435) 146 with a step-down from DAPT to single antiplatelet therapy with ticagrelor beyond the first month after PCI in an all-comers cohort with DES. The risks and benefits of shortening DAPT to 3 months or even shorter is another area with limited evidence.…”

Optimal duration of dual antiplatelet therapy after acute coronary syndromes and coronary stenting

“…Ongoing studies are examining novel strategies with DAPT including different treatment regimens, shorter DAPT durations in ACS and novel stent platforms. The GLOBAL LEADERS (NCT01813435),21 which is the largest of the ongoing clinical trials with DAPT, examines the efficacy of DAPT with ticagrelor plus aspirin for 1 month followed by 23 months of single treatment with ticagrelor compared with the standard 12 months of DAPT followed by aspirin monotherapy in patients after biolimus DES implantation. The TWILIGHT (NCT02270242) trial examines the safety of DAPT with ticagrelor and aspirin for 3 months and then ticagrelor alone versus the same DAPT regimen for 12 months.…”

Acute Coronary Stent Thrombosis in Modern Era: Etiology, Treatment, and Prognosis

“…Glycoprotein IIb/IIIa antagonists (eptifibatide, abciximab, and tirofiban) are also widely used in ACS patients with complicated lesions and high-risk AST; clinical observations showed that glycoprotein IIb/IIIa antagonists could effectively prevent AST [1,60]. Nowadays, several novel antiplatelet and anticoagulation drugs, such as prasugrel, dabigatran, apixaban and abciximab, ticagrelor and rivaroxaban, are paving their way for clinical use through randomized trials (GEMINI-ACS study and GLOBAL LEADERS trial); their applications in future clinical practice might enrich the therapy options and be helpful for more effective prevention and treatment of AST [61,62]. …”