Ticagrelor Monotherapy or Dual Antiplatelet Therapy After Drug‐Eluting Stent Implantation: Per‐Protocol Analysis of the GLOBAL LEADERS Trial
Authors: Gragnano Felice , Zwahlen Marcel , Vranckx Pascal , Heg Dik , Schmidlin Kurt , Hamm Christian , Steg Philippe Gabriel , Gargiulo Giuseppe , McFadden Eugene P. , Onuma Yoshinobu , Chichareon Ply , Benit Edouard , Möllmann Helge , Janssens Luc , Leonardi Sergio , Zurakowski Aleksander , Arrivi Alessio , Van Geuns Robert Jan , Huber Kurt , Slagboom Ton , Calabrò Paolo , Serruys Patrick W. , Jüni Peter , Valgimigli Marco , Windecker Stephan , Abdellaoui Mohamed , Adlam David , Akin Ibrahim , Gonzalez‐Trevilla Agustin Albarran , Almeida Manuel , Neto Pedro Alves Lemos , Aminian Adel , Anderson Richard , Andreae Rick , Angioi Michael , Asano Taku , Barbato Emanuele , Barlis Peter , Barraud Pascal , Benit Edouard , Bertrand Olivier , Beygui Farzin , Bolognese Leonardo , Botelho Roberto , Bouwman Coby , Bressers Marco , Brunel Philippe , Buszman Pawel , Buysschaert Ian , da Silva Pedro Canas , Carrie Didier , Cequier Angel , Chichareon Ply , Chang Chun Chin , Chowdhary Saqib , Collet Carlos , Colombo Antonio , Cotton James , Ferreira Rui Cruz , Curello Salvatore , Curzen Nick , de Bot Judith , de Vreede Tone , Karth Georg Delle , Dijksma Lynn , Dominici Marcello , Édes István , Eeckhout Eric , Eitel Ingo , Faluközy József , Fath‐Ordoubadi Farzin , Ferrario Maurizio , Fontos Geza , Diaz Jose Francisco , Quintella Edgard Freitas , Frey Bernhard , Friedrich Guy , Galasko Gavin , Galuszka Grzegorz , Ribeiro Vasco Gama , Garg Scot , Gargiulo Giuseppe , Geisler Tobias , Gelev Valeri , Ghandilyan Art , Goicolea Javier , Gori Tommaso , Gragnano Felice , Guimarães Ana , Hamm Christian , Haude Michael , Heg Dik , Heijke Pieter , Antolin Rosa Ana Hernández , Hildick‐Smith David , Hillen Dorien , Hoekman Ina , Hofma Sjoerd , Holmvang Lene , Hoole Stephen , Horváth Iván , Huber Kurt , Hugense Annemarie , Ibrahim Karim , Iñiguez Andres , Isaaz Karl , Jambrik Zoltán , Janssens Luc , Jasionowicz Pawel , Jonk Judith , Jung Werner , Jüni Peter , Katagiri Yuki , Kogame Norihiro , Koh Tian Hai , Koning René , Konteva Mariana , Kőszegi Zsolt , Krackhardt Florian , Kreuger Yvonne , Kukreja Neville , Ladan Boudijn , Lantelme Pierre , Leandro Sergio , Leibundgut Gregor , Liebetrau Christoph , Lindeboom Wietze , Miguel Carlos Macaya , Mach François , Magro Michael , Maillard Luc , Manavifar Negar , Mauri Laura , McFadden Eugene , Merkely Bela , Miyazaki Yosuke , Młodziankowski Adam , Moccetti Tiziano , Modolo Rodrigo , Möllman Helge , Morelle Jean‐François , Moschovitis Aris , Ottesen Michael Munndt , Muurling Martin , Naber Christoph Kurt , Neumann Franz‐Josef , Oldroyd Keith , Ong Paul , Onuma Yoshinobu , Palsrok Sanne , Petrov Ivo , Plante Sylvain , Prokopczuk Janusz , Rademaker‐Havinga Tessa , Raffel Christopher , Rensing Benno , Roffi Marco , Royaards Kees‐Jan , Sabate Manel , Schächinger Volker , Seidler Tim , Peñaranda Antonio Serra , Serruys Patrick , Sikarulidze Lali , Slagboom Ton , Soliman Osama I , Sousa Amanda , Spitzer Ernest , Stables Rod , Steg Gabriel , Steinwender Clemens , Subkovas Eduardas , Suryapranata Harry , Takahashi Kuniaki , Talwar Suneel , Teiger Emmanuel , Weele Addy Ter , Teurlings Eva , Thury Attila , Tijssen Jan , Tonev Gincho , Trendafilova‐Lazarova Diana , Tumscitz Carlo , Umans Victor , Ungi Imre , Valkov Veselin , van der Harst Pim , van Geuns Robert Jan , van Meijeren Cokky , Vassilev Dobrin , Velchev Vasil , Velthuizen Esther , Verheugt Freek , Vlcek Natalia , Dahl Jürgen Vom , Vrolix Mathias , Walsh Simon , Werner Nikos , Windecker Stephan , Witsenburg Maarten , Zaman Azfar , Żmudka Krzysztof , Zrenner Bernhard , Zurakowski Aleksander , Zweiker Robert 
Published: March 2022

Background
In the GLOBAL LEADERS trial, ticagrelor monotherapy beyond 1 month compared with standard antiplatelet regimens after coronary stent implantation did not improve outcomes at intention‐to‐treat analysis. Considerable differences in treatment adherence between the experimental and control groups may have affected the intention‐to‐treat results. In this reanalysis of the GLOBAL LEADERS trial, we compared the experimental and control treatment strategies in a per‐protocol analysis of patients who did not deviate from the study protocol.

Methods and Results

Baseline and postrandomization information were used to classify whether and when patients were deviating from the study protocol. With logistic regressions, we derived time‐varying inverse probabilities of nondeviation from protocol to reconstruct the trial population without protocol deviation. The primary end point was a composite of all‐cause mortality or nonfatal Q‐wave myocardial infarction at 2 years. At 2‐year follow‐up, 1103 (13.8%) of 7980 patients in the experimental group and 785 (9.8%) of 7988 patients in the control group qualified as protocol deviators. At per‐protocol analysis, the rate ratio for the primary end point was 0.88 (95% CI, 0.75–1.03;
P
=0.10) on the basis of 274 versus 325 events in the experimental versus control group. The rate ratio for the key safety end point of major bleeding was 1.00 (95% CI, 0.79–1.26;
P
=0.99). The per‐protocol and intention‐to‐treat effect estimates were overall consistent.

Conclusions
Among patients who complied with the study protocol in the GLOBAL LEADERS trial, ticagrelor plus aspirin for 1 month followed by ticagrelor monotherapy was not superior to 1‐year standard dual antiplatelet therapy followed by aspirin alone at 2 years after coronary stenting.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT01813435.