October 22, 2018
2 min read

GLOBAL LEADERS: Experimental antiplatelet therapy may benefit in ACS, but not in stable CAD

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Pascal Vranckx
Pascal Vranckx

SAN DIEGO — Among patients who had PCI with a drug-eluting stent, 1 month of combination ticagrelor and aspirin therapy followed by ticagrelor alone conferred better bleeding outcomes at 2 years than 1-year clopidogrel plus aspirin followed by 1-year aspirin monotherapy in patients with ACS, according to new data from the GLOBAL LEADERS study presented at TCT 2018.

However, 2-year bleeding outcomes did not differ between the antiplatelet strategies in patients with stable CAD, and the experimental strategy was not superior at 2 years for all-cause mortality or net adverse clinical events in either the ACS cohort or the stable CAD cohort.

“There is no indication for ticagrelor (Brilinta, AstraZeneca) as a single antiplatelet therapy or as part of a dual antiplatelet strategy in patients with stable coronary artery disease,” Pascal Vranckx, MD, PhD, medical director of the cardiac ICU at Hartcentrum Hasselt and a member of the faculty of medicine and life sciences at Hasselt University in Belgium, said during a presentation. “Ticagrelor as a single antiplatelet therapy in the first year after drug-eluting stent implantation in patients with acute coronary syndromes seems promising.”

As Cardiology Today’s Intervention previously reported, in the GLOBAL LEADERS trial of 15,980 patients scheduled to undergo PCI for stable CAD or ACS, the primary outcome of all-cause mortality or nonfatal Q wave MI confirmed by ECG at discharge did not differ between the antiplatelet strategies in the overall cohort at 2 years, nor did all-cause mortality or moderate to severe bleeding.

Vranckx presented an analysis of whether outcomes differed between patients with stable CAD and patients with ACS.

Kaplan-Meier estimates of 24-month all-cause mortality were similar between the antiplatelet strategies in patients with ACS (rate ratio [RR] = 0.87; 95% CI, 0.68-1.12) and in patients with stable CAD (RR = 0.9; 95% CI, 0.69-1.16; P for interaction = .88), he said.

In the ACS cohort, there were fewer Bleeding Academic Research Consortium (BARC) types 3 or 5 bleeding events at 24 months in those assigned the experimental strategy vs. those assigned the standard strategy (RR = 0.73; 95% CI, 0.54-0.98), but the same was not true in the stable CAD cohort (RR = 1.32; 95% CI, 0.97-1.81; P for interaction = .007), according to the researchers.

For 24-month net adverse clinical events, defined as all-cause mortality, investigator-reported MI or BARC types 3 or 5 bleeding, there was no difference between the strategies in the ACS cohort (RR = 0.9; 95% CI, 0.77-1.05) or the stable CAD cohort (RR = 1; 95% CI, 0.85-1.17; P for interaction = .38), Vranckx said.


At 1 year, the experimental strategy conferred reduced BARC types 3 or 5 bleeding events in the ACS cohort but not the stable CAD cohort (P for interaction = .009), but there were no other interactions by disease type, he said.

“A treatment-by-subgroup interaction was noted for BARC 3 or 5 bleedings at 24 months by clinical presentation, which seemed partially accounted for by a treatment-by-subgroup interaction for type of reference treatment,” Vranckx said during the presentation. “A treatment advantage for safety is suspected for the experimental strategy in patients with acute coronary syndromes in the first year against a ticagrelor-based reference strategy, and a disadvantage in patients with stable coronary artery disease compared against a clopidogrel-based reference strategy.” – by Erik Swain


Vranckx P, et al. Keynote Interventional Studies VIII: Pharmacotherapy trials and high bleeding risk patients. Presented at: TCT Scientific Symposium; Sept. 21-25, 2018; San Diego.

Disclosure: The study was sponsored by the European Cardiovascular Research Institute with grants from AstraZeneca, Biosensors and The Medicines Company. Vranckx reports he received consultant fees/honoraria from AstraZeneca, Bayer Healthcare, Daiichi Sankyo and Terumo, all unrelated to the present study.