Original Investigation
Ticagrelor Alone Versus Dual Antiplatelet Therapy From 1 Month After Drug-Eluting Coronary Stenting

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Abstract

Background

The GLOBAL LEADERS (GLOBAL LEADERS: A Clinical Study Comparing Two Forms of Anti-platelet Therapy After Stent Implantation) study randomly assigned 15,991 patients undergoing percutaneous coronary intervention to 1-month dual antiplatelet therapy (DAPT) followed by 23-month ticagrelor monotherapy or conventional 12-month DAPT followed by 12-month aspirin. Apart from Q-wave myocardial infarction (MI), all study endpoints were analyzed as investigator reported.

Objectives

This was a pre-specified ancillary study assessing whether experimental therapy is noninferior, and if met, superior, to conventional treatment for the coprimary efficacy endpoint of all-cause death, nonfatal MI, nonfatal stroke, or urgent target vessel revascularization and superior in preventing BARC 3 (Bleeding Academic Research Consortium) or 5 bleeding (coprimary safety endpoint) at 2 years with a 0.025 significance level to preserve nominal 5% alpha error.

Methods

An independent clinical event committee adjudicated investigator-reported and eventually unreported events of 7,585 patients from the 20 top-enrolling participating sites.

Results

The 2-year coprimary efficacy endpoint occurred in 271 (7.14%) and in 319 (8.41%) patients in the experimental and conventional groups, respectively (rate ratio [RR]: 0.85; 95% confidence interval [CI]: 0.72 to 0.99), fulfilling noninferiority (p noninferiority <0.001), but not superiority (p superiority = 0.0465). The rates of BARC 3 or 5 bleeding did not differ (RR: 1.00; 95% CI: 0.75 to 1.33; p = 0.986). A time-dependent treatment effect was observed with the experimental strategy being associated with a lower risk of MI (RR: 0.54; 95% CI: 0.33 to 0.88; p interaction = 0.062) and definite stent thrombosis (RR: 0.14; 95% CI: 0.03 to 0.63; p interaction = 0.007) after 1-year post-percutaneous coronary intervention.

Conclusions

Ticagrelor monotherapy after 1-month DAPT was noninferior, but not superior, to conventional treatment in the prevention of ischemic events, and it did not decrease major bleeding risk as compared with conventional treatment. (GLOBAL LEADERS Adjudication Sub-Study [GLASSY]; NCT03231059).

Key Words

adjudication
dual antiplatelet therapy
percutaneous coronary intervention
ticagrelor

Abbreviations and Acronyms

ACS
acute coronary syndrome
BARC
Bleeding Academic Research Consortium
CAD
coronary artery disease
CEC
clinical event committee
CI
confidence interval
DAPT
dual antiplatelet therapy
IR
investigator reported
MI
myocardial infarction
PCI
percutaneous coronary intervention
RR
rate ratio
ST
stent thrombosis
TVR
target vessel revascularization

Cited by (0)

Dr. McFadden has received personal fees and nonfinancial support from the University of Bern and Daiichi-Sankyo Europe; and has received travel grants from AstraZeneca and Menarini Ireland. Dr. Leonardi has received grants from AstraZeneca; and has received personal fees from AstraZeneca, Bayer, Chiesi, and Bristol-Myers Squibb/Pfizer. Dr. Vranckx has received personal fees from AstraZeneca, The Medicines Company, Terumo, CLS Behring, Daiichi-Sankyo, and Bayer Health Care. Dr. Serruys has received personal fees from Abbott, Biosensors, Cardialysis, Medtronic, Sinomedical Sciences, Philips/Volcano, Xeltis, and HeartFlow; and has received consultancy fees from Abbott Laboratories, Biosensors, Cardialysis, Medtronic, Sino Medical Sciences Technology, Philips/Volcano, Xeltis, and HeartFlow. Dr. Diletti has received grants from AstraZeneca. Dr. Naber has received personal fees from Abbott, Medtronic, Biosensors, and Biotronik. Dr. Hamm has received personal fees from and served on an Advisory Board for AstraZeneca. Dr. Steg has received grants from Bayer/Janssen, Merck, Sanofi, Servier, and Amarin; and has received consulting, speaking, or other personal fees from Merck, Sanofi, Amarin, Amgen, Bayer/Janssen, Servier, Bristol-Myers Squibb, Idorsia, Boehringer Ingelheim, Pfizer, Novartis, Regeneron, Eli Lilly, Novartis, Novo-Nordisk, AstraZeneca, and Servier. Dr. Jüni serves as an unpaid member of the steering group of trials funded by AstraZeneca, Biotronik, Biosensors, St. Jude Medical, and The Medicines Company; and has received research grants paid to his institution from AstraZeneca, Biotronik, Biosensors International, Eli Lilly and The Medicines Company; and has received and honoraria to the institution for participation in advisory boards from Amgen, but has not received personal payments by any pharmaceutical company or device manufacturer. Dr. Windecker has received grants from Amgen, Abbott, Biotronik, Bristol-Myers Squibb, Boston Scientific, Medtronic, Bayer, Edwards Lifesciences, St. Jude Medical, Terumo, Sinomed, and Polares. Dr. Valgimigli has received grants from Abbott, Medicure, Terumo, and AstraZeneca; and has received speaker fees and personal fees from Chiesi, Bayer, Daiichi-Sankyo, Amgen, Terumo, Alvimedica, AstraZeneca, Biosensors, and Idorsia. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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