GLOBAL LEADERS Adjudication Sub-Study

The GLOBAL LEADERS trial was designed to determine the benefits and risks of an antithrombotic regimen using ticagrelor 90 mg BID combined with low-dose (75 mg OD) acetylsalicylic acid (ASA) for one month followed by ticagrelor 90 mg BID alone for 23 months, compared to conventional dual antiplatelet therapy (DAPT) in all-comers patients with coronary artery disease undergoing biolimus-eluting stent implantation on bivalirudin. It was intended as a pragmatic clinical trial and, by design, endpoints included in primary and secondary analyses are only investigator-reported (IR) and will not undergo independent adjudication by a CEC. It is well known that in the absence of blinding of randomized treatment (i.e. in an open-label design such as GLOBAL LEADERS) the use of IR outcome may introduce detection and/or reporting bias. There are multiple lines of evidence indicating that central and independent adjudication of events may affect the results of a randomized trial by minimizing variability and heterogeneity inherently present when several different clinicians and data managers apply definitions of endpoints which are complex and sometimes not well known.Moreover, independent adjudication of ischaemic and bleeding endpoints may provide important mechanistic information that may deepen understanding of the primary endpoint result of the study by better characterizing component of such endpoints including, but not limited to, precise cause of death, sub-type of myocardial infarction (MI), and bleeding location. The objectives of this substudy are: to assess the impact of CEC-adjudication process on the results of the study; to quantify the added value of CEC adjudication process for endpoint reporting by evaluating the concordance between IR-reported and CEC-adjudicated events; to gather mechanistic information to aid in the interpretation of the effect of the experimental treatment in the parent trial and to identify specific subgroups of patients that could particularly benefit from the experimental therapy in terms of ischemic and bleeding events.